Friday, August 28, 2020
Gay Marriage Essay Example for Free
Gay Marriage Essay Gay relationships are an overall issue of should it be permitted or not in todayââ¬â¢s social orders and has been a point for a long time. Gay marriage is a marriage between two individuals of same sex or sexual orientation. There are states and nations that are against similarly just as for same sex marriage. It has been an issue about whether same sex couples ought to have the option to wed since 1971. It was later viewed as it was not legitimate for same sex marriage and custom for marriage in the United States has been planned as lawful responsibility between a man and a lady. Be that as it may, gay connections are progressively picking up the enthusiasm of acknowledgment in our nation. Vermont was the primary state to present common associations in July of 2002, and the principal state to legitimize same sex marriage without being required to do as such by court(Goodnough, A. 2009). A few states have considered a type of duty called common association; this is a type of relationship that is fairly similar to a marriage (About.com Guide, 2012). Common associations are lawful agreements between accomplices that are perceived by a state or government as presenting all or a portion of the rights gave by marriage, however without the understood authentic and strict importance related with the word ââ¬Å"marriageâ⬠(About.com Guide, 2012). They are not profited any of the government advantages of marriage, for example, standardized savings. This is as yet an issue for some strict individuals on the planet today who trust God made Adam and Eve not Adam and Steve. Numerous lawmakers have said they are against gay marriage however they surrender it over to the states to choose whether or not to help it. A few states have allowed restricted marriage advantages to gays yet call them household organizations. Society discusses how everybody ought to be dealt with reasonably, on account of rights and equity, however would prefer not to incorporate gay people. Well it is dishonest to not permit some portion of society the option to adore somebody justâ because that individual that they love might be of a similar sex. Gay people are individuals and they do have rights that ought not be prevented from securing them since certain individuals consider them extraordinary. Gay people love and need love simply like others and this is a need. Love is need and an ideal for every single individual. Or maybe you are getting it from a sibling, an auntie, or only a neighbor, we as people want this solitary a regular routine. At the point when we deny this by not permitting same sex couples to wed in light of the fact that the individual is of a similar sex, this is viewed as dishonest. Deontological morals contend rights and obligations. This would make same sex marriage wrong. Deontology says God doesn't care for homosexuality and that it's anything but a right, guaranteeing in light of the fact that the good book says this. In this contention, everybody doesn't have confidence in the book of scriptures and the good book is deciphered in such a large number of, numerous ways. So this truly makes for no genuine contention. Individuals who are against homosexuality will be for this contention. The contentions against gay marriage are beginning to be feeble. One contention is of marriage itself. One may contend that marriage is between a man and a lady. Marriage is a joining between two individuals who love one another and God. This genuinely makes it difficult to accept that it ought to be legal.Where another may state marriage is between two individuals who love each other regardless. Christians look and see that equivalent sex marriage is against Godââ¬â¢s will . A typical Christian is to follow the expression of God. A few Christians accept that the scriptural standards are antiquated and these wants ought not be changed. Christian supporters said that God instructed that his devotees don't participate in gay relations. Christians firmly accept that on the off chance that God state that something isn't right, at that point it isn't right. Christians should likewise peruse on to see that we are all godsââ¬â¢ youngsters and he acknowledges us for what our identity is. I thought God made all of us as equivalent. At that point there are the individuals who don't have faith in God and they may state that the book of scriptures is being deciphered wrong and individuals accept what they need to accept. They would state who are we to tell somebody who they cherish or wed. Removing gay people option to wed is contrary to the principles. Another contention would be that gays can't shoulder kids. Valid, they can't, however they can add to society by permitting kids to be brought up in a two parent home and kids will have a superior possibility a real existence. This assists a great deal of youngsters who are vagrants or cultivate kids. Ladies who cannotâ bare kids are permitted to receive and bring up youngsters, so for what reason are gay people any unique. The utilitarianism will say that there is an answer for this. In the event that we can have a marriage among highly contrasting races, for what reason would we be able to have a marriage between same genders? In the event that a marriage should be between two individuals who love one another and need to spend an amazing remainder together, at that point what is the issue? In the brain of an Utilitarian nobody in the general public can see or prognosticate who will have a relationship. In the event that equivalent sex marriage or connections are so off-base give a valid justification other than that it isn't the standard of religion. Utilitarianism will ask, ââ¬Å"How will same sex relationships hurt anyoneâ⬠? I don't accept that equivalent sex relationships will hurt any grown-up yet shouldn't something be said about the youngsters. Since same sex couples are permitted to embrace, there will be other kids out there asking questions and pondering for what reason they have two mothers or two fathers. On the off chance that everybody is made equivalent, should this incorporate the gays and lesbians? Disclosing to them that they don't reserve the option to wed is removing their human rights. Presently is removing somebody people right off-base? Guard of Marriage Act denies government acknowledgment of same sex marriage and permits states to decline to perceive such relationships acted in different states. The main states in the U.S. that perform relationships between same sex couples are Connecticut, District of Columbia, Iowa, Massachusetts, New Hampshire, New York and Vermont. In 2001, the Netherlands turned into the main nation to open the common union with same sex couples. Same sex couples are battling for the privilege of their human rights and to be dealt with reasonably gradually it is coming around for them. Moral pride differentiate that gay people getting an opportunity at adoration by marriage is a benefit, much the same as it is for any other person. This is right, it is correct. People reserve a privilege to pick the individual they need to spend an amazing remainder with, regardless of whether this individual is of a similar sex. At the point when the constitution was made, it not state special cases for specific rights to specific individuals, it is to the entirety of society. Individuals decide to be gay since they feel as though they were destined to be like this and for what reason would it be a good idea for anyone to attempt to change that? Gay may ask, ââ¬Å"Who would we say we are hurtingâ⬠? Gay people reserve a privilege to battle for what is directly for them and what they accept ought to be equallyâ given to them as people. In the event that they feel that it is directly for them to cherish an individual of a similar sex, at that point let them. They may feel that they are the best fit guardians for kids nowadays, since the two of them can bolster these youngsters and give them a glad life. Simultaneously, don't deny them what is legitimately theirs. Moral selfishness is a gay own idea as how same sex marriage is right however right since it doesn't hurt anybody and it is oneââ¬â¢s right. Same sex marriage is a continuous issue in view of numerous reasons. Individuals if todayââ¬â¢s society is starting to understand that it is smarter to become more acquainted with gay people and get them. They are the same as us all. Gay people live and inhale air simply like any ordinary person. They ought not be informed that they can't wed in light of the fact that the individual that they need to wed isn't who we figure they ought to wed. Homosexuality is a piece of the standards nowadays. In the event that society denies gay people the option to get hitched, at that point they are characterizing them of their privileges. This issue doesn't hurt any one individual whatsoever. Love is the thing that marriage is about, regardless of whether it is an equivalent sex couple or the other gender that is attempting to get hitched. I comprehend that a few people and Christians consider this to be a wrongdoing, yet judging is a transgression additionally and who are we to pass judgment. Individuals ought not pass judgment flippantly, and who saying that my grandmother utilizes, which means it might look terrible outwardly, however when you open it and read it you get an alternate story. Gay people are extraordinary to society and ought to be given the option to wed regardless. Everything comes down to; God is the one in particular who can truly rebuff them in the event that it is really off-base to wed a similar sex. Perhaps sanctioning same sex marriage will influence the world or possibly not. Presently this appears to be extremely silly to me, yet you never know. I do consider this to be an issue with duplicating however. Guardians of a similar sexuality can't have kids. There are some acceptable contention and some awful contentions with regards to the issue of sanctioning same sex relationships. There will come a day that the world will think of a choice that will make everybody upbeat or possibly not. References Mosser, K (2010).Introduction to morals and social duty, San Diego, Bridgepoint Education www.thepublicphilospher.com/humanrights-and-gaymarriage Davidson.edu/commomplace/Christian-moral argumentsregarding-same-sex-marriag es www.ashfordlibrary www.balancepolitics.org/samesexmarriage Hansen, V. Moral Argument for sanctioning gay marriage, (2012) Head, T. Marriage and Rights, (2012)
Saturday, August 22, 2020
Menes Was the First Pharaoh of Egypt
Menes Was the First Pharaoh of Egypt The political unification of Upper and Lower Egypt happened around 3150 B.C., a large number of years before students of history started to record such things. Egypt was an old progress even to the Greeks and Romans, who were as far expelled in time from this early time of Egypt as we are from them today. Who was the primary pharaoh to join Upper and Lower Egypt? As indicated by the Egyptian history specialist Manetho, who lived in the late fourth century B.C. (the Ptolemaic time frame), the author of the bound together Egyptian state which consolidated Upper and Lower Egypt under a solitary government was Menes. Be that as it may, the specific personality of this ruler stays a riddle. Was Narmer or Aha the First Pharaoh? There is basically no notice of Menes in the archeological record. Rather, archeologists are uncertain whether ââ¬Å"Menesâ⬠ought to be recognized as either Narmer or Aha, the first and second rulers of the First Dynasty. The two rulers are credited at various occasions and by various sources with the unification of Egypt. Archeological proof exists for the two prospects: the Narmer Palette unearthed at Hierakonpolis appears on one side King Narmer wearing the crown of Upper Egypt-the tapered white Hedjet-and on the opposite side wearing the crown of Lower Egypt-the red, bowl-molded Deshret. In the interim, an ivory plaque unearthed at Naqada bears both the names ââ¬Å"Ahaâ⬠and ââ¬Å"Menâ⬠(Menes). A seal impression found at Umm el-Qaab records the initial six leaders of the First Dynasty as Narmer, Aha, Djer, Djet, Den and [Queen] Merneith, which recommends that Narmer and Aha may have been father and child. Menes is never observed on such early records. He Who Endures By 500 B.C., Menes is referenced as getting the seat of Egypt legitimately from the god Horus. In that capacity, he comes to possess the job of establishing figure much as Remus and Romulus did from old Romans. Archeologists concur that almost certainly, the unification of Upper and Lower Egypt happened over the rules of a few First Dynasty rulers, and that the legend of Menes was, maybe, made at an a lot later date to speak to those included. The name ââ¬Å"Menesâ⬠implies ââ¬Å"He Who Endures,â⬠and it might have come to indicate the entirety of the proto-dynastic lords who made unification a reality. Different Sources The Greek antiquarian Herodotus, in the fifth century B.C., alludes to the main ruler of a brought together Egypt as Minâ and claims that he was liable for the depleting of the plain of Memphis and establishing the Egyptian capital there. Itââ¬â¢s simple to see Min and Menes as a similar figure. Also, Menes was credited with presenting the love of divine beings and the act of penance to Egypt, two signs of its human advancement. The Roman author Pliny acknowledged Menes for the acquaintance of composing with Egypt too. His accomplishments carried a time of imperial extravagance to Egyptian culture, and he was berated for this during the rules of reformers, for example, Teknakht, in the eighth century B.C.
Friday, August 21, 2020
Foundation of Human Resources Management - annotated bibliography Essay
Establishment of Human Resources Management - clarified list of sources - Essay Example Are they updating their HR capacities?, and so on. The creator proceeds to show that without effectiveâ human capital, associations are probably going to have next to zero income. The HR capacity can include an incentive by embracing a control-and-review job. In any case, Lawler recommends that two different jobs that HRM can take on permit it to include more noteworthy worth. The first is the familiarâ human assets the executives job. The second is the job of colleague, which stresses creating frameworks and practices to guarantee that a companysâ human assets have the required skills and inspiration to perform successfully. Enunciated in a reasonable and succinct composition style, the book fills in as a helpful review of HR capacities. This diary article by Hargis and Bradley digs into key parts of HRM in upstarts. They contend that when business people and business administrators build up a marketable strategy, they distinguish that an incredible line of items or administrations enables an organization to accomplish, and support, an upper hand. They proceed to refer to the effective organizations, for example, Coyote Logistics, W.L. Blood and Associates and Zappos.com to put forth their defense. They further propose that fruitful directors likewise perceive the significance of productively dealing with their representatives and creating theirâ human assets. These organizations obviously connected theirâ human asset managementâ practices to their serious plan of action. At the point when business pioneers can adjust a solid serious procedure to a very much planned and deliberately focusedâ human asset framework, it has the vital establishment that acquires clients the entryway (or to their site) at first and ge ts them to return for rehash business. The article is elegantly composed and offers key bits of knowledge into the key job of HRM in youngster organizations. Job hypothesis has been utilized successfully by scientists in the fields of brain research, social brain science, human science, association conduct, and human asset the board since the early
Tuesday, May 26, 2020
New Step by Step Roadmap for Research Paper Service Reviews
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Friday, May 15, 2020
As An Asian American Born Citizen, It Never Really Was
As an Asian American born citizen, it never really was hard to ââ¬Ëfit-inââ¬â¢ or adapt to the environment, where I would consider myself as part of the popular culture--a dynamic culture based in large, heterogeneous societies permitting considerable individualism, innovation, and change (Jordan, 2014). Consequently, my ancestors from the older generation would be considered as part of the folk culture--small rural, cohesive, conservative, isolated, largely self-sufficient groups that are homogeneous in custom and ethnicity. Considering both cultures, I can see the difference and the evolution of future generations. In the current century, race, ethnicity and nationality are put into context, mixing everything together and creating somethingâ⬠¦show more contentâ⬠¦Whilst if I was in China, I would be focused on education, and preparing for my future job, and then focusing on how I am going to live the rest of my life. In relation, when I was younger, I was taken to a pr ivate preschool and Kindergarten, in hopes that I am able to build a stronger foundation for when I enter the first grade. As I grew older, and first grade came near, my family moved from one city to another to enroll me in a better elementary school. From this, part of my educational background grew. Throughout the years, we would fly to China to visit family and I was then exposed to the different cultures and was able to compare the living standards and cultural aspects between the United States and China. Consequently, my momââ¬â¢s side is Tai-Shan and my dadââ¬â¢s side is Shanghainese. On my momââ¬â¢s side, I have ancestors from Guangzhou, Tai-Shan, Beijing, and Hong Kong. On my dadââ¬â¢s side, I have ancestors from Guangzhou, Shanghai, Beijing, and Hong Kong as well. I know that these cities are all within China and have rigorous living conditions, intense education systems, and a place where money is everything. From this, I can say that this does influence my ide ntity, as I am exposed to these cultures and ideas quite often. Being Chinese, and the first generation to be here in the United States, my parents are still quite traditional. Through that, the idea of who I am is influenced and altered, because there are ideas that IShow MoreRelatedRacism : Racism And Racism1181 Words à |à 5 PagesThis issue of racism is popular by name but tends to be sugar coated by the way people see it. In order to truly understand racism you need to take a bite into the topic in order to get a taste of what it is really like. Racism comes in many different forms and can be seen many different ways. But why even care about racism at all? Why does it even matter? One would think that with such a harsh background regarding racism in America it would no longer exist in society today. But sadly that is notRead MoreImmigration : What Is Immigration?1271 Words à |à 6 Pages They want to become citizens of the new country. The number of people who immigrate to a new country is very large. In 2009, over 200 million people changed countries. That sounds like a lot of people. Actually, that is only three of every one hundred citizens of the world or 3%. The rest of the citizens of the world stayed in their own countries. Lots of immigrants have trouble in their new homes. My family are immigrants. They came here with my older sister when she was 4 years old. My parentsRead MoreAnalysis of Joy Luck Club Essay750 Words à |à 3 PagesAnalysis of Joy Luck Club Ask any typical-looking Asian students around campus whether they are Chinese or Japanese and the reply will probably be universal: Neither, Im Chinese-American. 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The problem that African American people experience here is that they feelRead MoreThe Influence Of Gang Affiliation On The Family Structure2687 Words à |à 11 PagesThis boundary was also a factor that lead Raoul to joining a gang in his youth. He affectionately referred to them as the ââ¬Å"homeboysâ⬠and didnââ¬â¢t go into too much detail about their activities (and I was afraid to pry) but his membership in this gang was one of the things that got him into trouble and negatively influenced his educational attainments. Raoul grew up in Sanger, surrounded by other Mexican immigrants who were in the same low-economic cycle and poor neighborhoods as he was and his parents
Wednesday, May 6, 2020
Summary of Chua 1986 - 635 Words
Summary of Chua 1986 Authors main point Provide two alternative world views and their underlying assumptions are elucidated ââ¬â interpretive and the critical. Discuss consequences of conducting research within these philosophical traditions through a comparison between accounting research that is conducted on the same problem but from two different perspectives. Deal briefly with the difficulties associated with these alternative perspectives Authorââ¬â¢s purpose To change the emphasis of mainstream accounting research from hypothetico-deductivism and technical control assumptions to alternative views and obtain a fundamentally different and potentially rich research insights. Aim 1. To enable accounting researchers to self-reflectâ⬠¦show more contentâ⬠¦ideographic) 2. society ââ¬â characterizes it as orderly or subject to fundamental conflict Burell and Morgan (1979) Four paradigms used to classify accounting theories * Functionalist * Interpretive * Radical humanist * Radical structuralist Problems persisted so accounting perspectives are differentiated with reference to underlying assumptions about knowledge, the empirical phenomena under study, and the relationship between theory and the practical world of human affairs. A classification of assumptions ââ¬Å"knowledge is produced by people, for people, and is about people and their social and physical environmentâ⬠Beliefs about knowledge Epistemological assumptions * Decide what to count about acceptable truth by specifying the criteria and process of assessing truth claims * E.g. an epistemological assumption might state that a theory is considered true if it is repeatedly not falsifiable by empirical events Methodological assumptions * Indicate that research methods deemed appropriate for the gathering of valid evidence. * E.g. large-scale sample surveys or laboratory experiments that are ââ¬Å"statistically soundâ⬠may be considered acceptable research methods. Both sets of assumptions are closely related. What is a ââ¬Å"correctâ⬠research method will depend on how truth is defined. Belief about physical and social reality Ontology Object of Study * People may be viewed as identical to physical objects and beShow MoreRelatedManagement Accounting And Practices Of Small And Medium Enterprises5055 Words à |à 21 PagesManagement accounting was first known as cost accounting. This origin was reflected in the earlier title for practitioners of cost or works accountants (Wilson and Chua, 1988). Accounting historians have long endorsed the view that cost accounting is a product of the industrial revolution (Johnson, 1981). For example (Wilson and Chua, 1993) claimed that cost accounting was practiced by the mechanized, multi process, cotton textile factories that appeared in England and United States around 1800.Read MoreInformation Technology and Accounting4117 Words à |à 17 Pages(Teng Calhoun, 1996) to become an important part of how companies manage and control their resources. Organizations are responding in different ways and at different rates to the wide range of IT based opportunities and pressures (Joh nson et al., 1986). Decisions regarding the building of technical IT architecture should be closely linked to decisions made in designing the IT organisation that should be linked to the organisational design of the company itself. 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This wealth is created by individuals who assume the major risks in terms of equity, time, and/or career commitment of providing value for some product or serviceRead MoreVolkswagen20284 Words à |à 82 PagesDISSERTATION XIAOFENG WEN TABLE OF CONTENTS 1.0 INTRODUCTION 1.1 Introduction 1.2 Introduction of Topic 1.3 Research Objective and Research Questions 1.4 Available Research Method 1.5 Limitation of Research 1.6 The Structure of Dissertation 1.7 Summary 8 8 8 9 10 10 11 12 2.0 LITERATURE REVIEW 2.1 Introduction 2.2 Key Entry Modes and Influential Factors 2.3 The Review of Foreign Direct Investment 2.31 Definition of Foreign Direct Investment 2.32 Knowledge about FDI and Key Factors AffectingRead MoreDiffereces Between Vietnamese and American Compliment10198 Words à |à 41 Pagesfacts which is must be do either truly or falselyâ⬠( J.L Austin, How to do thing with words, p.1). In fact, there are some utterances we cannot decide whether it is ââ¬Å"trueâ⬠or ââ¬Å"falseâ⬠. For example: E.g. Giá » muá »â¢n thá º ¿ nà y mà há » chà °a ra nhá »â°? (It is so late, why they did not come) (Thá º ¡ch Lam, Già ³ lá º ¡nh Ãâá º §u mà ¹a) In this situation, when Mrs. Ti talks to Lien, this question functions not only as what a question shouldRead MoreCase Studies67624 Words à |à 271 Pagespopulation and growth areas of the United States. The impact of minimills on the industry is best demonstrated by looking at the former industry leader US Steel (now USX Corp.). In 1966, US Steel controlled 55 per cent of the American steel market; in 1986 it controlled only 17 per cent. Despite its inauspicious foray into steel, Nucor Corp. has become the benchmark for both the US steel industry and US industry in general. Nucor is one of the fastest growing and most efficient steel producers in the
Tuesday, May 5, 2020
Civil Rights Movement 1890
Civil Rights Movement: 1890-1900 1890: The state o Essay f Mississippi adopts poll taxes and literacy tests to discourage black voters. 1895: Booker T. Washington delivers his Atlanta Exposition speech, which accepts segregation of the races. 1896: The Supreme Court rules in Plessy v. Ferguson the separate but equal treatment of the races is constitutional. 1900-1910 1900-1915: Over one thousand blacks are lynched in the states of the former Confederacy. 1905: The Niagara Movement is founded by W.E.B. du Bois and other black leaders to urge more direct action to achieve black civil rights. 1910-1920 1910: National Urban League is founded to help the conditions of urban African Americans. 1920-1930 1925: Black nationalist leader Marcus Garvey is convicted of mail fraud. 1928: For the first time in the 20th century an African American is elected to Congress. 1930-1940 1931: Farrad Muhammad establishes in Detroit what will become the Black Muslim Movement. 1933: The NAACP files -and loses- its firs suit against segregation and discrimination in education. 1938: The Supreme Court orders the admission of a black applicant to the University of Missouri Law School 1941: A. Philip Randoph threatens a massive march on Washington unless the Roosevelt administration takes measures to ensure black employment in defense industries; Roosevelt agrees to establish Fair Employment Practices Committee (FEPC). 1942: The congress of Racial Equality (CORE) is organized in Chicago. 1943: Race riots in Detroit and Harlem cause black leaders to ask their followers to be less demanding in asserting their commitment to civil rights; A. Philip Randolph breaks ranks to call for civil disobedience against Jim Crow schools and railroads. 1946: The Supreme Court, in Morgan v. The Commonwealth of Virginia, rules that state laws requiring racial segregation on buses violates the Constitution when applied to interstate passengers. 1947: Jackie Robinson breaks the color line in major league baseball. 1947: To Secure These Rights, the report by the Presidents Committee on Civil Rights, is released; the commission, appointed by President Harry S. Truman, recommends government action to secure civil rights for all Americans. 1948: President Harry S. Truman issues an executive order desegregating the armed services. 1950-1960 1950: The NAACP decides to make its legal strategy a full-scale attack on educational segregation. 1954: First White Citizens Council meeting is held in Mississippi. 1954: School year begins with the integration of 150 formerly segregated school districts in eight states; many other school districts remain segregated. 1955: The Interstate Commerce Commission bans racial segregation in all facilities and vehicles engaged in interstate transportation. 1955: Rosa Parks is arrested for refusing to give up her bus seat to a white person; the action triggers a bus boycott in Montgomery, Alabama, let by Martin Luther King Jr. 1956: The home of Martin Luther King Jr. is bombed. 1956: The Montgomery bus boycott ends after the city receives U. S. Supreme Court order to desegregate city buses. 1957: Martin Luther King Jr. and a number of southern black clergymen create the Southern Christian Leadership Conference (SCLC). 1958: Ten thousand students hold a Youth March for Integrated Schools in Washington, D.C. 1959: Sit-in campaigns by college students desegregate eating facilities in St. Louis, Chicago, and Bloomington, Indiana; the Tennessee Christian Leadership Conference holds brief sit-ins in Nashville department stores. 1960-1970 1960: Twenty-five hundred students and community members in Nashville, Tennessee, stage a march on city hallthe first major demonstration of the civil rights movementfollowing the bombing of the home of a black lawyer. 1960: John F. Kennedy is elected president by a narrow margin. 1961: Martin Luther King Jr. and President John F. Kennedy hold a secret meeting at which King learns that the new president will not push hard for new civil rights legislation. 1962: Ku Klux Klan dynamite blasts destroy four black churches in Georgia towns. 1962: President Kennedy federalizes the National Guard and sends several hundred federal marshals to Mississippi to guarantee James Merediths admission to the University of Mississippi Law School over the opposition of Governor Ross Barnett and other whites; two people are killed in a campus riot. 1963: Black students Vivian Malone and James Hood enter the University of Alabama despite a demonstration of resistance by Governor George Wallace; in a nationally televised speech President .
Wednesday, April 15, 2020
Economic Development in Indonesia
Introduction In the 1960s, the economy of Indonesia deteriorated due to political instability. This led to increased poverty and hunger. In the mid 1960ââ¬â¢s the economy was in bad shape with 1000% inflation, minimal investment, low export revenues, poor infrastructure and companies were operating at a very low capacity.Advertising We will write a custom research paper sample on Economic Development in Indonesia specifically for you for only $16.05 $11/page Learn More When the president Sukarno failed the new order administration worked hard and brought the Indonesiaââ¬â¢s economy back on track in the mid 1960ââ¬â¢s. The recent government brought an extent of discipline in economy which reduced inflation, suspended foreign debt, helped to stabilize the currency, engrossed foreign aid and investment (Fane, 2003). The raised oil prices made the economy of Indonesia to grow with a 7% from 1968 to 1981. GDP per capital grew at 545% from 1970 to 198 0 as result of increased oil export revenues. The economy growth since then has been accelerating. Despite this growth there are problems that keep dragging economic growth behind. These includes the wide spread corruption, low foreign investments, exploitation and destruction of natural resources, health issues among others (Natasha, 2001). This paper will focus on inflation, environmental issues and health issues as the biggest problems in Indonesia. Environmental issues The problem is due to large scale deforestation and wildfire; there is also over exploitation of marine resources, high population has contributed greatly to the environmental problems. Environment preservation is important as it contributes to economic development. Good environment that is free from deforestation and pollution is good for agricultural production. Agriculture contributes to economic growth of a country. The increase in population in the country has resulted to a strain in the resources of the coun try to appoint that they have made the country fall in the trap of resources misuse. Deforestation and wildfires has contributed to desertification leading to hungry population (Miller, 1997). A lot of money is being used to restore back the good environment and this has been leading slow economic development as a lot of money is being used in environment conservations and preservation.Advertising Looking for research paper on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More In 1983, an area that was estimated to be equivalent of 30,000km2 or an amount of $10 billion was burnt in Kalimantan Timur Province as a result of wild fire; this affected the economy growth as it led to environmental disaster, other than China and United state, Indonesia comes in third as the major emitter of green house gasses; this can be attributed to the way they clear their bushes; by burning. Air pollution in Indonesia is high and it is leading to public health issues. Inflammation of respiratory system is linked to air pollution and it greatly leading to death in Indonesia. Water quality in Indonesia is deteriorating as there are no good sewerage systems in urban area (Miller, 1997). Health issues Indonesia has a high population and many people are living with HIV/AIDS. This has great impact on healthcare systems in the country and it is leading to economic crisis and problems with resource allocation. HIV/AIDS has been affecting the productive age group between 15-45 years leading to early deaths and high population of orphans. This has led to increased poverty and food insecurity. The drugs that are being used to reduce multiplication of the virus are also too expensive and this is affecting the countryââ¬â¢s economic development. Tuberculosis is the second most communicable disease that is causing death in Indonesia. It is approximated that 175,000 people die due to tuberculosis each an every year. Malaria is anoth er disease that has remained a problem and causing many deaths every year. All this diseases are indeed a problem in economic development as a lot of resources are being allocated in their prevention and treatment (Fane, 2003). Inflation As a result of political exertions inflation has persistently been an economic predicament in Indonesia. The country has gone through very high levels of inflation estimated at 1000% inflation between1964 and1967. As a result the country suffered from harsh poverty and hunger. Even though the economy improved swiftly under the new order government, inflation has constantly been greater than 10% per annum (World Bank, 2008). Though the economy grew as a result of high revenue from oil exports, inflation has persisted leading to wider economic gap among Indonesians.Advertising We will write a custom research paper sample on Economic Development in Indonesia specifically for you for only $16.05 $11/page Learn More Inflatio n has been higher than economic growth and this has lead to high level of poverty. The government has been attempting to lessen inflation during economic recuperation and development. In the year 2010, inflation was at 7% higher than economic growth which was 6%. This is greatly affecting Indonesians especially middle class who cannot afford to buy food when prices increase. This is indeed a problem in Indonesia as it is leading to increased poverty (Natasha, 2001). Policies In environmental issues the government introduced plantation of trees to cover for deforestation. The plantation trees included coffee, palm and rubber. This was in attempt to replace the original forest cover although it was not that successful. In the mid1980s the government joined World Bank to develop forestry management plans. This led to first forest inventory, development of national parks and conservation programs, seminal forestry plans and development of master plan by food and agriculture organization of United Nations (Miller, 1997). Use of fire to clear land for agriculture has been prohibited as it has been leading to emission of greenhouse gases. Efforts are being put to reduce deforestation and forest degradation although this has not been successful because of increased population and industrialization. Human activities are increased due to high population that is demanding large lands for agriculture. This puts environment at risk leading to desertification and low rainfall thus agricultural produce is reduced leading to a hungry population (Deutser, 2002). In health issues, polices have been put in place to prevent diseases such as HIV/AIDS, Tuberculosis and malaria as they are leading to high morbidity and mortality rates in Indonesia. When the economy grew from 1968 to 1998 the government invested in prevention and curative measure in health and this lead to reduction in mortality rate from142 per1000 in 1968 to 50 per 1000 in 1998.Advertising Looking for research paper on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More The economic crises have lead to slow development in health systems. The administration has taken extraordinary steps in defending the health of its populace by transforming its seventy five year plan, but the progress in resolving health problems has been dawdling (World Bank, 2008). In communicable diseases the government has introduced programs like population education on these diseases with the aim of prevention. All age groups are being educated on communicable diseases such as HIV/AIDS, Tuberculosis, sexually transmitted diseases, and malaria among others. The population is being educated on their causes, prevention and they are being advised to seek medical attention on time in order to reduce mortality rate. Although Indonesia has prioritized health promotion and prevention of these diseases, the policies are being implemented very slowly and thus they are ineffective (Natasha, 2001). To correct the inflation the new order administration put a lot of effort and this led to increased revenue from oil exports. This led to reduced inflation as economy grew rapidly. The export oriented industrialization also assisted in dropping inflation. Though the economic development in Indonesia has been improving, inflation has not been eliminated completely because there was great impact on its economy during its political instability (Deutser, 2002). Recommendation To avoid environmental issues that are hindering economic growth, the government should invest in educating the population on importance of conserving environment. Environmental studies should be introduced to schools at an early stage to ensure the population learn the importance of environment to the countryââ¬â¢s economy. Heavy penalties and regulations should be put in practise for people charged with deforestation and polluting environment. Rules and regulations should be set on waste disposal for manufacturing companies to avoid environment pollution especially water pollution which leads to po isoning of fish. To avoid health issues the government should hire more medical personnel to educate the population on prevention of communicable diseases. This will ensure all the population is well educated on prevention and this lowers the costs incurred in buying drugs for curing diseases which could have been avoided through prevention. To avoid increased rates of inflation the government and politicians should avoid political instability recurring as it leads to high rate of inflation which has been hard to recover from. The government should encourage private and foreign investors in order to gain more revenue in effort to recover from inflation. Also export oriented manufacturing should be practised to earn extra revenue for the country. Conclusion The biggest problems in Indonesia have been environmental issues which has lead to degradation of environment. This has been mainly due to deforestation and wildfire. This has been leading to poor agricultural production and emiss ion of greenhouse gases. The government has put in place rules of reforestation which have not been applied because of high population. The population should be educated on importance of conserving the environment (Miller, 1997). Health issues have been another problem in Indonesia as they have lead to high mortality and morbidity rates. The government has invested in preventive and curative measures though they have been implemented slowly due to few medical personnel compared to the high population. The government should employ more medical staff to educate population on prevention of communicable diseases. Inflation is still a problem in Indonesia despite the continuous economic growth. The government should avoid recurrence of political instability which led to high inflation. References Deutser, P. (2002). Survey of Recent Development. Bulletin of Indonesian Economic Studies, 1(1).1. Fane, G. (2003). Change and Continuity in Indonesiaââ¬â¢s New Fiscal Decentralization Arrang ements. Bulletin of Indonesian Economic Studies, 1(1).1. Miller, J. (1997). Deforestation in Indonesia and the Orangutan Population. TED Case Studies, 1(1),1. Natasha, H. (2001). Anti-Corruption Strategies in Indonesia. Bulletin of Indonesian Economic Studies, 1(1),1. World Bank. (2008). Indonesia: Economic and Social update. Retrieved from www.worldbank.org This research paper on Economic Development in Indonesia was written and submitted by user Nancy Lindsay to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.
Thursday, March 12, 2020
Leaders of the American Revolution
Leaders of the American Revolution The American Revolution began in 1775 and led to the rapid formation of American armies to oppose the British. While British forces were largely led by professional officers and filled with career soldiers, the American leadership and ranks were filled with individuals drawn from all walks of colonial life. Some American leaders, such as George Washington, possessed extensive service in the militia, while others came directly from civilian life. The American leadership was also supplemented by foreign officers recruited in Europe, though these were of varying quality. During the early years of the conflict, American forces were hampered by poor generals and those who had achieved their rank through political connections. As the war wore on, many of these were replaced as competent and skilled officers emerged. American Revolution Leaders: American Major General William Alexander, Lord Stirling - noted brigade, division, and department commanderLieutenant Colonel Ethan Allen - Commander, Green Mountain Boys during 1775 attack on Fort TiconderogaMajor General Benedict Arnold - noted field commander, famously changed sides in 1780 becoming one of historys best-known traitorsCommodore John Barry - noted naval commanderBrigadier General George Rogers Clark - Conqueror of the Old NorthwestMajor General Horatio Gates - Commander, Northern Department, 1777-1778, Southern Department, 1780Colonel Christopher Greene - Commander at Fort Mercer, Battle of Red BankMajor General Nathanael Greene - Commander, Continental Army in the South (1780-1783)Commodore John Paul Jones - Key American naval commanderMajor General Henry Knox - American artillery commanderMarquis de Lafayette - Noted French volunteer in American serviceMajor General Charles Lee - Controversial American field commanderMajor General Henry Light Horse Harry Lee - noted Americ an cavalry/light infantry commander Major General Benjamin Lincoln - Commander, Southern Department (1778-1780)Brigadier General Francis Marion - The Swamp Fox - Noted guerilla leaderBrigadier General Hugh Mercer - American general killed in 1777Major General Richard Montgomery - Promising American general killed at the Battle of QuebecBrigadier General Daniel Morgan - Key commander at Saratoga and CowpensMajor Samuel Nicholas - Founding Officer, US Marine CorpsBrigadier General Count Casimir Pulaski - Father of the America CavalryMajor General Arthur St. Clair - Commander at Fort Ticonderoga, 1777Major General John Stark - Victor of BenningtonMajor General Baron Friedrich von Steuben - Inspector General, Continental ArmyMajor General John Sullivan - Division Commander (1776-1778), Commander, Rhode Island (1778), Sullivan Expedition (1779)General George Washington - Commander in Chief, Continental ArmyMajor General Anthony Wayne - Daring American commander who saw extensive service American Revolution Leaders - British Major John Andre - British spymasterLieutenant General John Burgoyne - British commander at the Battle of SaratogaGovernor Major General Sir Guy Carleton - British Governor of Quebec (1768-1778, commander-in-chief in America (1782-1783)General Sir Henry Clinton - British commander-in-chief in America (1778-1782)Lieutenant General Lord Charles Cornwallis - British commander in the South, forced to surrender at the Battle of YorktownMajor Patrick Ferguson - inventor of the Ferguson rifle, commander at the Battle of Kings MountainGeneral Thomas Gage - governor of Massachusetts, commander-in-chief in America (1775)Vice Admiral Richard Howe - Commander, North American Station (1776-1778)General Sir William Howe - British commander-in-chief in American (1775-1778)Admiral Lord George Rodney - British naval commanderLieutenant Colonel Banastre Tarleton - noted British cavalry commander
Tuesday, February 25, 2020
Technology impact on children in USA Research Paper
Technology impact on children in USA - Research Paper Example Rather than spending loads of time on computer and TV, it is also vital for children to spend their time on other activities. It can also create negative impact on children. Children spending large sum of time on television and Computer are prone to become fat. Despite having some negative impact, computer games can help children to learn new things. Children find it easier to learn from technology. Computer games also have some negative impact on children. Some violent games can affect the mentality of children and would sometimes lead to increase in aggressive behavior and increase in aggressive feelings. Real world violence shown in many violent games can change the behavior of children in to aggressive. Some survey revealed that maximize use of social networking sites and inter net can lead to aloneness and depression. Children are too small to visualize the difference between real world and virtual world. Violent aggressive response shown in game games can make create difficulty on mind of children to verify difference of simulation and real world. Technology holds a pivotal role for the development of children to teenager. Technology can have positive and negative impact on growth of children to teenager. In has been surveyed in the year 1999, percentage of children having gaming console in 67%. 60% of the children have home computers. And more than 37% of children are so me way or another connected to internet. Recent survey reveals the popularity and addiction of computer and internet among children. Children aged between 8 and 18 are asked that, if they are taken in to desert isle then what things they would carry with them. Most of the children replied access to internet and computer. The addiction and popularity of technology had made children lazier. The increase in exposure to electronic devices would create negative impact on the development of children at younger age. Technology is not the solution that would
Saturday, February 8, 2020
MPH599 - Culminating Project Mod 4Case Assignment Essay
MPH599 - Culminating Project Mod 4Case Assignment - Essay Example In doing so, they have data on what is being done and what is working. Involving a representative can only improve the work to be done. The Centers for Partnerships and Strategic Alliance also would be a helpful group to involve as they are involved in some of the granting that is being done for this problem and may be of great help to this group in determining funding that might be available. The NIHCM is a non-profit organization whose mission it is to promote improvement in health care access, management and quality and to foster dialogue and find creative workable solutions to American Health System Problems (nihcm.org). Further ASTHO which is a national nonprofit organization representing the state and territorial public health agencies of the US, US Territories, and District of Columbia (ASTHO.org). There is of course a need for involvement of the children themselves and their parents as anything that comes out of this affect them in some way. Physicians, School nurses and the health care community need to be involved as they are the primary people to carry out any of the plans or principles that come from this. They will also be the data collectors. The local community, schools, and Universities will need to determine how they can help with playgrounds and safe walking and biking trails. Finding tax money to make these improvements may be necessary and involving this group ahead of time will make that process easier. Last but not least are the schools and their contract with the vending machine industry. It makes no sense at all for a child to eat healthy food in the cafeteria and then be able to go out in the hall to get M&Ms. Of course, we know that this is a livelihood for many of these people but what will be needed is for them to change the kind of snacks that are available here. This includes things like Coke and Pepsi machines. This will not be an easy task, however, involving them early in the process will help the process become more
Thursday, January 30, 2020
Confrontational level Essay Example for Free
Confrontational level Essay Shown by Helens sheer lack of thought for her daughter Jo, she has no consideration for her feelings. She continually ensures the suppression of her daughter and at one stage has the audacity to express this on a confrontational level. I have to consider something far more important than your feelings.(Pg 1)à This is further confirmation of Helens severe disrespect and heartlessness towards her daughter. An attitude which stemmed from her initial rejection to motherhood and forthcoming child. She blames Jo for her divorce-her birth being the event that revealed Helens unfaithfulness to the husband she described as a retard. In my judgement, she has not learnt to handle her problems and take full responsibility for her immoral doings. This has proven very costly in both her and her daughters lives. Cathies mothers consideration for her can be described as the other end of the extreme. Her calm, quiet approach to the situation reveals how valuable she sees their relationship; enough not to be damaged in a way that Helen made possible.à The fact that Helen doesnt know much about her daughter and Cathies mother feels she knows her daughter is of significance in their relationship. Helens reaction to Jos personal drawings was one of shock, yet pleasant surprise. I didnt realise I had such a talented daughter.à This demonstrates not only the fact that she hasnt spent quality time learning and bonding with her daughter, but the sad reality that Helen hasnt desired to. Prior to the above quote, Helen implied that she expected her daughter to tell her everything about herself she has a right to know.à I thought you said you werent good at anythingà Here, we see that Helen has just taken Jos word for the matter; she has simply accepted it and not bothered to know otherwise.à The fact that some daughters are able to talk to their mothers about boyfriends/relationships shows the closer friendship a mother and daughter can share. Helen didnt know whether or not Jo ad a boyfriend, and this mirrors the lack of confidence Jo has in Helen as a Mother, let alone a friend. Helen doesnt seem to possess A Mothers Fondness the built-in, unconditional, love and interest a Mother has in the welfare of their child. On the other hand, Cathies mother feels that she knows her child all too well. She is confident that her daughter wouldnt understand her if she showed she was angry:à I knew that she would not see my anger, as love for herà The Mothers maternal instincts lead her to believe something was not right when her daughter didnt arrive home on time. This shows that Cathie is respectful of her Mothers wishes to be home on time. Her mother is familiar with her character and feels she knows her. She says:à she would have poured to tell me if she was going away anywhere.à When each Mother-daughter relationship begins to encounter difficulty, the Mothers react differently. Cathies Mum blames herself for her daughters behaviour. She is fully aware of her parental responsibilities/duties. She knows that her actions have a deep impact on her daughter and their relationship status. I had failedit was my fault she was as she was. I had brought myself pain.à The Mother distinguishes the problem and wants to make amends to their estranged relationship. She does her best to prevent yet another hurtful row and keeps silent; praying it wont happen again.à Helen however, (as mentioned previously) doesnt spare a single thought for her daughters feelings. She quite willingly expresses her thoughts and emotions in a rude and obnoxious manner and openly declares that she is not responsible for her daughter or their situation.à Have I ever laid claim to being a proper mother.à This quote shows that she is not hypocritical about herself, which in a way is a good thing. However, there is nothing positive about Helens approach to motherhood. Unlike Cathies Mother who blames herself, Helen points her finger at Jo:à Its your fault In act__scene__, Helen attempts to justify her reasons for neglecting Jo.à QUOT à The way in which the daughters are portrayed in the text differ in that so much sympathy is evoked in the audience for Jo. She has had to live her life and grow up without a true Mother. She has not had someone to look up to, someone to show her love and be a backbone, especially during the time of adolescence. The atmosphere at the flat is one of hopelessness, tension and distress, which is why we feek sirr for her. SETTING ON STAGE In A Mothers Fondness we sympathise with the Mother as she cares so much for her daughter who feels as if she doesnt.à Despite the many differences in each mother-daughter relationship, there are also many similarities. One of which is the way both daughters use some form of escapism to avoid facing up to their problems. When Cathie learned that her mum had been everywhere looking for her, she asked her friend Elaine if she could stay and not return home. She had missed two busses and expected that her mum would be very upset with her. She would be furiousThis meant another row.à Elaine, I dont want to go home. Cant I stay here?à It is evident from this quote that Cathie would rather remain with her friend, away from home and the prospect of another argument with her mother. This teaches the audience that the disagreements she had with her mother were emotionally very damaging she couldnt bear another instance wherein she and her mother were on bad terms.à Unlike Cathie, Jo recites nursery rhymes for fun with Geoff. This can be read into and analysed in a psychological sense: the nursery rhymes bring her laughter, which aids in transporting her to the childhood she never enjoyed. You look like a spratt. Jack Spratt, whod eat no fat, his wife would eat no lean and so between then both, you see, they licked the platter clean. Did u enjoy that dramatic recitation? (pg51)à Her question at the end prompts a positive response from Geoff who doesnt want to deflate her cheerful mood. She encourages that he joins in, wanting someone to play with as it were.à You say one We can imagine that this was said with a happy expectant look upon her face. Geoff then proceeds to recite another rhyme and upon completion, she expresses how much she enjoyed it: I like that. Do you know any more?à Jo is keen that this playful, childlike interaction between them continues. She gets much more out of it than would any other average person. The fun factor and distraction nursery rhymes brought about were doing her good she was not dwelling upon thoughts of her broken family.à Both Jo and Cathie feel as though they are not receiving enough care and attention they want to feel loved. This is another similarity found in each relationship. During the car journey Cathie and her mother made home, they remained silent (as previously highlighted). Though most other teens resent the fact that in the same situation, their mums would talk endlessly about how worried they were and so on, Cathie would rather that was the case. I was angryshe was acting as if nothing had happenedShe simply didnt care about meà In any relationship, it is important that there is balance between certain factors. Cathie and her mum are at one end of the extreme maintaining their silence no fuss. This is the absolute opposite to Jo and Helen who are at the other end of the extreme.à In Jos case, she threatens to jump out of the window in order to determine whether or not Helen cares about her. She wants to hear someone does actually care for her. Her desperation and longing for love is made evident in her dramatic actions. Jo is aware that the concept of actions speaking louder than words is never going to be a reality for her. Therefore she resorts to grabbing any ounce of love Helen had to offer her even it was mere words. This attention seeking is to be expected from Jo, as Helen never really gave Jo a mothers love. We can be certain that a lack of communication is common within each relationship. Weve seen how Cathies mother found it difficult to express her upset to her daughter and visa versa. We also know that the effects of this were negative: Cathie felt that her mother didnt care for her, and her mother felt that Cathie hated her. The two of them are alike in that they pretend that everything is ok between them when there are clearly important issues to be tackled and discussed. It is important that each mother and daughter feel they can talk to each other on a mature and serious level. At times, we see Jo making attempts to do so. However, Helen does not respond to this very well and is constantly changing the subject showing her inability to listen to her daughter.
Tuesday, January 21, 2020
The Crucible - How John Proctor Changed Essay -- Essay on The Crucible
The Crucible - How John Proctor changed throughout the storyline from mistreating his wife by cheating on her while she was ill with Abigail, to someone who took the blame so no one else got in trouble. The Crucible In this essay I will talk about how John Proctor changed throughout the storyline from mistreating his wife by cheating on her while she was ill with Abigail, to someone who took the blame so no one else got in trouble. The Crucible is based on the true story of the 1692 Salem Witch Trials where people were hanged if they were accused of being a witch. All of them were innocent and wrongly hanged. Arthur Miller has changed some of the play so it would be easier to write about like the girls in crying out has been reduced and Abigail's age has been raised. There were also 7 judges of equal authority which has all been symbolized in Hathorne and Danforth. The story starts out with a group of girls who were caught dancing in the woods by Reverend Parris. He also saw one of them naked in the woods. Next morning Betty falls ill and Parris keeps asking what's wrong with her and what did Abigail do to her. He asks about the devil and Abigail sees this as an opportunity to blame people for being involved with the devil and getting her own back on people. We then see people coming into the house and leaving. Abigail tells all these people who she saw with the devil. Later on we get introduced to John Proctor who was respected in Salem and even feared. He is in his middle thirties and was a farmer. Then in Act2 John Proctor sits down to dinner with his wife, Elizabeth. Mary Warren, their servant, has gone to the witch trials, disobeying Elizabeth's order that she remain in the house. Fourteen... ...eople were acting quickly. At the beginning everybody speaks with the same dialect. He uses goody for names which is short for good wife. And people call each other with mister and miss. This all contributes to the feeling of a different society. Distanced not only by time but by the way it communicated. While we was reading it in class, there was some people who thought that John Proctor took the easy way out and was being selfish by committing suicide and leaving his children and wife to them selves and not standing up to the rest of the village by knowing that people wouldn't like him anymore and if he died then he wouldn't have to put up with that. I think though that he changed during the play and did what was right by trying to do his best and make up to his wife about his mistakes. He changes and tries to take the blame instead of everyone else.
Monday, January 13, 2020
Phylogenetic
Molecular Phylogenetics An introduction to computational methods and tools for analyzing evolutionary relationships Karen Dowell Math 500 Fall 2008 Molecular Phylogenetics Karen Dowell 1 Abstract Molecular phylogenetics applies a combination of molecular and statistical techniques to infer evolutionary relationships among organisms or genes.This review paper provides a general introduction to phylogenetics and phylogenetic trees, describes some of the most common computational methods used to infer phylogenetic information from molecular data, and provides an overview of some of the many different online tools available for phylogenetic analysis. In addition, several phylogenetic case studies are summarized to illustrate how researchers in different biological disciplines are applying molecular phylogenetics in their work. Introduction to Molecular PhylogeneticsThe similarity of biological functions and molecular mechanisms in living organisms strongly suggests that species descended from a common ancestor. Molecular phylogenetics uses the structure and function of molecules and how they change over time to infer these evolutionary relationships. This branch of study emerged in the early 20th century but didnââ¬â¢t begin in earnest until the 1960s, with the advent of protein sequencing, PCR, electrophoresis, and other molecular biology techniques.Over the past 30 years, as computers have become more powerful and more generally accessible, and computer algorithms more sophisticated, researchers have been able to tackle the immensely complicated stochastic and probabilistic problems that define evolution at the molecular level more effectively. Within past decade, this field has been further reenergized and redefined as whole genome sequencing for complex organisms has become faster and less expensive. As mounds of genomic data becomes publically available, molecular phylogenetics is continuing to grow and find new applications. 4, 10, 17, 20, 22] The primary objective of molecular phylogenetic studies is to recover the order of evolutionary events and represent them in evolutionary trees that graphically depict relationships among species or genes over time. This is an extremely complex process, further complicated by the fact that there is no one right way to approach all phylogenetic problems. Phylogenetic data sets can consist of hundreds of different species, each of which may have varying mutation rates and patterns that influence evolutionary change.Consequently, there are numerous different evolutionary models and stochastic methods available. The optimal methods for a phylogenetic analysis depend on the nature of the study and data used. [5, 19, 20] Molecular Evolution: Beyond Darwin Evolution is a process by which the traits of a population change from one generation to another. In On the Origin of Species by Means of Natural Selection, Darwin proposed that, given overwhelming evidence from his extensive comparative analysis of living specimens and fossils, all living organisms descended from a common ancestor.The bookââ¬â¢s only illustration (see Figure 1) is a tree-like structure that suggests how slow and successive modifications could lead to the extreme variations seen in species today. [11, 27] Molecular Phylogenetics Karen Dowell 2 Figure 1. Evolution Defined Graphically. The sole illustration in Darwinââ¬â¢s Origin of the Species uses a tree-like structure to describe evolution. This drawing shows ancestors at the limbs and branches of the tree, more recent ancestors at its twigs, and contemporary organisms at its buds. [34] Darwinââ¬â¢s theory of evolution is based on three underlying principles: ariation in traits exist among individuals within a population, these variations can be passed from one generation to the next via inheritance, and that some forms of inherited traits provide individuals a higher chance of survival and reproduction than others. [11] Although Darwin developed his theory of evolution without any knowledge of the molecular basis of life, it has since been determined that evolution is actually a molecular process based on genetic information, encoded in DNA, RNA, and proteins. At a molecular level, evolution is driven by the same types of mechanisms Darwin observed at the species level.One molecule undergoes diversification into many variations. One or more of those variants can be selected to be reproduced or amplified throughout a population over many generations. Such variations at the molecular level can be caused by mutations, such as deletions, insertions, inversions, or substitutions at the nucleotide level, which in turn affect protein structure and biological function. [11, 22] What is a Phylogeny? According to modern evolutionary theory, all organisms on earth have descended from a common ancestor, which means that any set of species, extant or extinct, is related.This relationship is called a phylogeny, and is represented by phyloge netic trees, which graphically represent the evolutionary history related to the species of interest (see Figure 2). Phylogenetics infers trees from observations about existing organisms using morphological, physiological, and molecular characteristics. Figure 2. Phylogeny of Mammalia. This phylogenetic tree shows the evolutionary relationships among six orders of Mammalian species (taxa). Taxa listed in grey are extinct. The ââ¬Å"tree of lifeâ⬠represents a phylogeny of all organisms, living and extinct.Other, more specialized species and molecular phylogenies are used to support comparative studies, test biogeographic hypotheses, evaluate mode and timing of speciation, infer amino acid sequence of extinct proteins, track the evolution of diseases, and even provide evidence in criminal cases. [19] Molecular Phylogenetics Karen Dowell 3 Understanding Phylogenetic Trees Before exploring statistical and bioinformatic methods for estimating phylogenetic trees from molecular data , itââ¬â¢s important to have a basic familiarity of the terms and elements common to these types of trees. See Figure 3. ) Figure 3. Basic elements of a phylogenetic tree. Phylogenetic trees are composed of branches, also known as edges, that connect and terminate at nodes. Branches and nodes can be internal or external (terminal). The terminal nodes at the tips of trees represent operational taxonomic units (OTUs). OTUs correspond to the molecular sequences or taxa (species) from which the tree was inferred. Internal nodes represent the last common ancestor (LCA) to all nodes that arise from that point.Trees can be made of a single gene from many taxa (a species tree) or multi-gene families (gene trees). [1, 10] A tree is considered to be ââ¬Å"rootedâ⬠if there is a particular node or outgroup (an external point of reference) from which all OTUs in the tree arises. The root is the oldest point in the tree and the common ancestor of all taxa in the analysis. In the absence of a known outgroup, the root can be placed in the middle of the tree or a rootless tree may be generated. Branches of a tree can be grouped together in different ways. (See Figure 4. ) Figure 4.Groups and associations of taxonomical units in trees. A monophyletic group consists of an internal LCA node and all OTUs arising from it. All members within the group are derived from a common ancestor and have inherited a set of unique common traits. A paraphyletic group excludes some of its descendents (for examples all mammals, except the marsupialia Molecular Phylogenetics Karen Dowell 4 taxa). And a polyphyletic group can be a collection of distantly related OTUs that are associated by a similar characteristic or phenotype, but are not directly descended from a common ancestor. 1, 17] Trees and Homology Evolution is shaped by homology, which refers to any similarity due to common ancestry. Similarly, phylogenetic trees are defined by homologous relationships. Paralogs are homologous s equences separated by a gene duplication event. Orthologs are homologous sequences separated by a speciation event (when one species diverges into two). Homologs can be either paralogs or orthologs. [1, 11, 22] Molecular phylogenetic trees are drawn so that branch length corresponds to amount of evolution (the percent difference in molecular sequences) between nodes. 1, 19] Figure 5. Understanding paralogs and orthologs. Paralogs are created by gene duplication events. (See Figure 5. ) Once a gene has been duplicated, all subsequent species in the phylogeny will inherit both copies of the gene, creating orthologs. Interestingly, evolutionary divergence of different species may result in many variations of a protein, all with similar structures and functions, but with very different amino acid sequences. Phylogenetic studies can trace the origin of such proteins to an ancestral protein family or gene. [1, 22] Figure 6. Mirror Phylogenies.Gene A and Gene A1 are paralogs, whereas all i nstances of Gene A are orthologs of each other in different Canid species. One way to ensure that paralogs and orthologs are appropriately referenced in a phylogenetic tree, and guard against misrepresentation due to missing or incomplete taxonomic information is to generate mirror phylogenies (see Figure 6) in which paralogs serve as each otherââ¬â¢s outgroup. [1, 4, 19, 22] Estimating Molecular Phylogenetic Trees Molecular phylogenetic trees are generated from character datasets that provides evolutionary content and context.Character data may consist of biomolecular sequence alignments of DNA, RNA, or amino acids, molecular markers, such as single nucleotide polymorphisms (SNPs) or restriction fragment length polymorphisms (RFLPs), morphology data, or information on gene order and content. Evolution is modeled as a process that changes the state of a character, such as the type of nucleotide (AGTC) at a Molecular Phylogenetics Karen Dowell 5 specific location in a DNA sequence ; each character is a function that maps a set of taxa to distinct states. 1, 19] Note that most of the examples in this paper use DNA sequences as character data, but trees can be accurately estimated from many different types of molecular data. Figure 7. Evolution of a DNA Sequence Figure 7 illustrates how a molecular sequence might evolve over time as a result of multiple mutations that results small, but evolutionarily important changes in a nucleotide sequence. At the protein level, these changes may not initially affect protein structure or function, but over time, they may eventually shape a new purpose for a protein within divergent species. 10, 19, 22] OTUs can be used to build an unrooted phylogenetic tree that clearly depicts a path of evolutionary change. Steps in Phylogenetic Analysis Although the nature and scope of phylogenetic studies may vary significantly and require different datasets and computational methods, the basic steps in any phylogenetic analysis remain t he same: assemble and align a dataset, build (estimate) phylogenetic trees from sequences using computational methods and stochastic models, and statistically test and assess the estimated trees. 4, 19, 20] Assemble and Align Datasets The first step is to identify a protein or DNA sequence of interest and assemble a dataset consisting of other related sequences. For example, to explore relationships among different members of the Notch family of proteins, one might select DNA sequences for Notch1 through Notch4, in different species, such as human, dog, rat, and mouse, then perform a multiple sequence alignment to identify homologies. [1, 10, 13, 19, 20] There are a number of free, online tools available to simplify and streamline this process. DNA sequences of interest can be retrieved using NCBI BLAST or similar search tools.When evaluating a set of related sequences retrieved in a BLAST search, pay close attention to the score and E-value. A high score indicates the subject seque nce retrieved with closely related to the sequence used to initiate the query. The smaller the E-value, the higher the probability that the homology reflects a true evolutionary relationship, as opposed to sequence similarity due to chance. As a general rule, sequences with E-values less than 10-5 are homologs of a query sequence. [10] Once sequences are selected and retrieved, multiple sequence alignment is created.This involves arranging a set of sequences in a matrix to identify regions of homology. Typically, gaps (one or more spaces in the alignment) are introduced in one or more sequences to represent insertions or deletions in the molecular code that may have occurred over time. Effective multiple sequence alignment hinged on gap analysisââ¬âdetermining where to insert gaps and how large to make them. There are many websites and software programs, such as ClustalW, MSA, MAFFT, and T-Coffee, designed to perform multiple sequence on a given set of molecular data. ClustalW i s currently the most mature and most widely used. 1, 10. 19] Molecular Phylogenetics Karen Dowell 6 Building Phylogenetic Trees To build phylogenetic trees, statistical methods are applied to determine the tree topology and calculate the branch lengths that best describe the phylogenetic relationships of the aligned sequences in a dataset. Many different methods for building trees exist and no single method performs well for all types of trees and datasets. The most common computational methods applied include distance-matrix methods, and discrete data methods, such as maximum parsimony and maximum likelihood. 4, 17, 20] There are several software packages, such as Paup*, PAML, PHYLIP, that apply most popular methods. [4] Paup* is a commercially available program that implements a wide variety of methods for phylogenetic inference, including maximum likelihood analysis for DNA data using different models. Paup* also includes a set of exact and heuristic methods for searching optimal trees. PAML (Phylogenetic Analysis by Maximum Likelihood) is open-access set of programs for phylogenetic analysis and evolutionary model comparison.PAML includes many advanced modelsââ¬âDNA- and AAbased models as well as codon-based models that can be used to detect positive selection. Many of the programs in PAML can model heterogeneity of evolutionary rates among sequence sites using ? distributions, and evolutionary dynamics of different sequence regions (concatenated gene sequences). PHYLIP is another large suite of open-access programs for phylogenetic inference that estimates trees using numerous methods, including pairwise distance, maximum parsimony, and maximum likelihood.The maximum likelihood programs can handle a few simple stochastic models and have good tree searching capabilities. PHYLIP is generally considered good educational software for novice phylogeneticists. Distance-Matrix Methods Distance matrix methods compute a matrix of pairwise ââ¬Å"distancesâ⬠between sequences that approximate evolutionary distance. Distance-based methods tend to be in polynomial time and are quite fast in practice. These methods use clustering techniques to compute evolutionary distances, such as the number of nucleotide or amino acid substitutions between sequences, for all pairs of taxa.They then construct phylogenetic trees using algorithms based on functional relationships among distance values. There are several different distance-matrix methods, including the Unweighted Pair-Group Method with Arithmetic Mean (UPGMA), which uses a sequential clustering algorithm; the Transformed Distance Method, which uses an outgroup as a reference, then applies UPGMA; the Neighbor-Relations Method, which applies 4point condition to adjust the distance matrix, then applies UPGMA; and the Neighbor-Joining Method, which arranges OTUs in a star, the finds neighbors sequentially to minimize total length of tree. 4, 17] The following section on the UPGMA method prov ides a more detailed example of how distance-matrix methods work. UPGMA Method UPGMA produces rooted trees for which the edge lengths can be viewed as times measured by a molecular clock with a constant rate. This method uses a sequential clustering algorithm to identify two OTUs that are most similar (meaning they have the shortest evolutionary distance and are most similar in sequence) and treat them as a single new composite OTU. This process is repeated iteratively until only two OTUs remain.The algorithm defines the distance (d) between two clusters Ci and Cj as the average distance between pairs of sequences from each cluster: Molecular Phylogenetics Karen Dowell 7 Where |Ci| and |Cj| are the number of sequences in clusters i and j. This sequential clustering process is visually described in Figure 8. In this example, the two most homologous sequences are 1 and 2. They are clustered into a new composite parent node (6), and the branch lengths (t1 and t2) are defined as 1/2d1,2 . The next step is to search for the closest pair among remaining sequences and node 6.Pair 4 and 5 are identified and clustered into a new parent node (7), and the branch length for t4 and t5 is calculated. [4, 17] Figure 8. Sequential clustering of sequences using the UPGMA method. [17] In this interactive process, parent node 8 is created from pairs 7 and 3, and parent node 9 is created by clustering nodes 6 and 8. [4, 17] Thus, all sequences are clustered into a single evolutionary tree. The total time (t9) can be calculated as: D6,8 = 1/6 (d1,3 + d1,4 + d1,5 + d2,3 + d2,4 +d2,5)Discrete Data Methods Discrete data methods examine each column of a multiple sequence alignment dataset separately and search for the tree that best represents all this information. Although distance-based methods tend to be much faster than discrete data methods, they typically yield little information beyond the basic tree structure. Discrete data analyses, on the other hand, are information rich. The se methods produce a separate tree for each column in the alignment, so it is possible to trace the evolution for specific elements within a given sequence, such as catalytic sites or regulatory regions. 10, 17, 19, 20) Commonly used discrete data methods include maximum parsimony, which searches for the most parsimonious tree that requires the least number of evolutionary changes to explain differences observed, maximum likelihood, which requires a probabilistic model for the process of nucleotide substitution, and Bayesian MCMC, which also requires a stochastic model of evolution, but creates a probability distribution on a set of trees or aspects of evolutionary history. [17, 19, 20] Discrete data methods are generally considered to produce the best estimates of evolutionary history.However, these methods can be computationally expensive, and it can take weeks or months to obtain a reasonable level of accuracy for moderate to large datasets with 100 or more OTUs. [19] Molecular P hylogenetics Maximum Parsimony Karen Dowell 8 Among the most widely used tree-estimation techniques, maximum parsimony applies a set of algorithms to search for the tree that requires the minimum number of evolutionary changes observed among the OTUs in the study. For example, Figure 9 lists four sample sequences from which phylogenetic trees could be inferred using maximum parsimony.Site Seq 1 2 3 4 1 A A A A 2 A G G G 3 G C A A 4 A C T G 5 G G A A 6 T T T T 7 G G C C 8 C C C C 9 A G A G Figure 9. Sample sequences for a maximum parsimony study [17] Maximum parsimony algorithms identify phylogenetically informative sites, meaning the site favors some trees over others. Consider the sequences in Figure 9: Site 1 is not informative, because all sequences at that site (in column 1) are A (Adenine), and no change in state is required to match any one sequence (1-4) to another.Similarly, Site 2 is not informative because all three trees require one change and there is no reason to favor one tree over another. Site 3 is not informative because all three trees require two changes. (See Figure 10). Figure 10. Site 3 trees all require one evolutionary change. [17] Site 4 is not informative because all three trees require three changes. No one tree can be identified as parsimonious. (See Figure 10 Figure 11. Site 4 trees all require three evolutionary changes. [17] Site 5 is informative because one tree requires only one nucleotide change, whereas the other two trees require 2 changes.In Figure 12, the first tree on the left, which requires only one nucleotide change, is identified as the maximum parsimony tree. Figure 12. Site 5 trees vary in the number of evolutionary changes required. [17] Molecular Phylogenetics Maximum Likelihood Karen Dowell 9 The maximum likelihood method requires a probabalistic model of evolution for estimating nucleotide substitution. This method evaluates competing hypotheses (trees and parameters) by selecting those with the highest likeliho od, meaning those that render the observed data most plausible. The ikelihood of a hypothesis is defined as the probability of the data given that hypothesis. In phylogeny reconstruction, the hypotheses are the evolutionary tree (its topology and branch lengths) and any other parameters of the evolutionary model. [17, 20] The likelihood calculations required for evolutionary trees are far from straightforward and usually require complex computations that must allow for all possible unobserved sequences at the LCA nodes of hypothesized trees. This method specifies the transition probability from one nucleotide state to another in a time interval in each branch.For example, for a one-parameter model with rate of substitution ? per site per unit time, the probability that the nucleotide at time t is i is: The probability that the nucleotide at time t is j is: To set up a likelihood function, given x as the ancestral node and y and z as internal nodes, the probability of observing nucle otides i, j, k, l at the tips of the tree is computed as: Pxl(t1+t2+t3)Pxy(t1)Pyk(t2+t3)Pyz(t2)Pzi(t3)Pzj(t3) For the ancestral node (root) x, the probability of having nucleotide l in sequence 4 is calculated as: Pxl(t1+t2+t3)Because x, y, and z can be any one of four nucleotides (ACGT), it is necessary to sum over all possibilities to obtain the probability of observing the configuration of nucleotides i, j, k, l, in sequences 1, 2, 3, 4, for a given hypothetical tree (see Figure 13. ). This likelihood probability is calculated as: h(I,j,k,l)= [? gxPxl(t1+t2+t3)] [? Pxy(t1)Pyk(t2+t3)] [? Pyz(t2)Pzi(t3) Pzj(t3)] The appropriate likelihood function depends on the hypothetical tree and the evolutionary model used. (See Figure 13. ) [17] Figure 13. Different types of model trees for the derivation of the maximum likelihood function. 17] Molecular Phylogenetics Stochastic Models of Evolution Karen Dowell 10 Evolutionary changes in molecular sequences result from mutations, some of whic h occur by chance, others by natural selection. Rates of change can also differ among OTUs, depending on several factors ranging from GC content to genome size. To accurately estimate phylogenetic trees, assumptions must be made about the substitution process and those assumptions must be stated in the form of a stochastic evolutionary model. These probabilistic models are used to rank trees according to likelihood: P(data|tree).From a Bayesian perspective, they rank trees according to a posterior probability: P(tree|data). [17, 20] The objective of probabilistic models is to find likelihood or posterior probability of a particular taxonomic feature, then define and compute: P(x? |T,t ? ) Where x ? is xj for j=1â⬠¦n, T is a tree with n leaves with sequence j at leaf j, and t ? are tree edge lengths. [17] A few popular stochastic models of evolution include the single parameter Jukes-Cantor (JC) method, Kimura 2-parameter (K2P), Hasegawa-Kishino-Yano (HKY), and Equal-Input.Some s oftware programs, such as Paup*, will automatically use a default model for the tree estimation method chosen. The JC method is the easiest one to comprehend, because it assumes that if a site changes its state, it changes with equal probability to the other states. This is not very realistic, however, as some sites are known to evolve more rapidly than others, and some sites may be invariable and not allowed to change at all. Determining how best to select the appropriate model is a topic of another paper (or papers) as there is no one model that incorporates all mutation rules and patterns across different species and macromolecules. 4, 17, 20] Hidden Markov Models Profile hidden Markov models (HMMs) are a form of Bayesian network that provides statistical models of the consensus structure of a sequence family. Gary Churchill at The Jackson Lab was the first evolutionary geneticist to propose using profile HMMs to model rates of evolution. Many software packages and web services n ow apply HMMs to estimate phylogenetic relationships. [8] In the HMM format, each position in the model corresponds to a site in the sequence alignment. For each position, there are a number of possible states, each of which corresponds to a different rate of evolution.In addition, transitions between all possible rate-states at adjacent positions. Transition probabilities capture any tendency for patterns of rates to occur in successive sites. [2, 4] Assessing Trees Tree estimating algorithms generate one or more optimal trees. This set of possible trees is subjected to a series of statistical tests to evaluate whether one tree is better than another ââ¬â and if the proposed phylogeny is reasonable. Common methods for assessing trees include the Bootstrap and Jackknife Resampling methods, and analytical methods, such as parsimony, distance, and likelihood.To illustrate how these methods are used, consider the steps involved in a bootstrap analysis. Bootstrap Analysis A bootstra p is a statistical method for assessing trees that takes its name from the fact that it can ââ¬Å"pull itself up by its bootstrapsâ⬠and generate meaningful statistical distributions from almost nothing. Using bootstrap analysis, distributions that would otherwise be difficult to calculate exactly are estimated by repeated creation and analysis of artificial datasets. In a Non-parametric bootstrap, artificial datasets Molecular Phylogenetics Karen Dowell 11 generated by resampling from original data.In a parametric bootstrap, data is simulated according to hypothesis tested. The objective of any bootstrap analysis is to test whether the whole dataset supports the tree. [1, 4, 17] Figure 14 illustrates the basic steps in any bootstrap analysis. Sample datasets are automatically generated from an original dataset. Trees are then estimated from each sample dataset. The results are compiled and compared to determine a bootstrap consensus tree. Figure 14. Steps in a phylogenetic tr ee bootstrap analysis. [1] Phylogenetic Analysis Tools There are several good online tools and databases that can be used for phylogenetic analysis.These include PANTHER, P-Pod, PFam, TreeFam, and the PhyloFacts structural phylogenomic encyclopedia. Each of these databases uses different algorithms and draws on different sources for sequence information, and therefore the trees estimated by PANTHER, for example, may differ significantly from those generated by P-Pod or PFam. As with all bioinformatics tools of this type, it is important to test different methods, compare the results, then determine which database works best (according to consensus results, not researcher bias) for studies involving different types of datasets.In addition, to the phylogenetic programs already mentioned in this paper, a comprehensive list of more than 350 software packages, web-services, and other resources can be found here: http://evolution. genetics. washington. edu/phylip/software. html. PANTHER ( pantherdb. org) Protein ANalysis Through Evolutionary Relationships, known by its acronym PANTHER, is a library of protein families and subfamilies indexed by function. Panther version 6. 1 contains 5547 protein families. Molecular Phylogenetics Karen Dowell 12It categorizes proteins by evolutionary related proteins (families) and related proteins with same function (subfamilies). [8, 21, 26] PANTHER is composed of both a library and index. The library is a collection of ââ¬Å"booksâ⬠that represent a protein family as a collection of multiple sequence alignments, HMMs, and a family phylogenetic tree. Functional divergence within the tree is represented by dividing the parent tree into child trees and HMMs based on shared functions. These subfamilies enable database curators to more accurately capture functional divergence of protein sequences as inferred from genomic DNA. 25, 26] PANTHER database entries are annotated to molecular function, biological process and pathway with a proprietary PANTHER/X ontology system, which is supposed to be easier to understand than the more global standard Gene Ontology (GO). Database entries in PANTHER are generated through clustering of UniProt database using a BLAST-based similarity score. Trees are automatically generated based on multiple sequence alignments and parameters of the protein family HMMs using the Tree Inferred from Profile Score (TIPS) clustering algorithm.Scientific curators review all family trees, annotate each tree, and determine how best to divide them into subtrees using a tree-attribute viewer that tabulates annotations for sequences in a tree. In addition, trees and subfamilies are manually cross-checked and validated by curators. [25, 26] P-POD (ortholog. princeton. edu) The Princeton Protein Orthology Database (P-POD) combines results from multiple comparative methods with curated information culled from the literature.Designed to be a resource for experimental biologists seeking evolutionary information on genes on interest, P-POD employs a modular architecture, based on their Generic Model Organism Database (GMOD). P-POD can be accessed from their web service or downloaded to run on local computer systems. [12] P-POD accepts FASTA-formatted protein sequences as input, and performs comparative genomic analyses on those sequences using OrthoMCL and Jaccard clustering methods. The P-POD database contains both phylogenetic information and manually curated experimental results.The site also provides many links to sites rich in human disease and gene information. This tool may be particularly helpful for bioinformaticists and statisticians developing comparative genomic database tools and resources. Pfam (pfam. sanger. ac. uk/) PFam is a collection of protein families represented by multiple sequence alignments and HMMs. It contains models of protein clans, families, domains, and motifs, and uses HMMs representing conserved functional and structural domains. It is a large, widely used, actively curated mature database that has been available online since 1995.Pfam can be used to retrieve the domain architectures for a specific protein by conducting a search using a protein sequence against the Pfam library of HMMs. This database is also helpful for proteomes and protein domain architecture analysis. [6, 8, 24] There are two versions of the Pfam database: Pfamââ¬âB is generated automatically from ProDom, using PsiBLAST, an open access bioinformatics tool available through NCBI for identifying weak, but biologically relevant sequence similarities. Pfam-A is hand-curated from custom multiple sequence alignments. Pfam protein domain families are clustered with Mkdom2, and aligned with ProDomAlign.ProDom is a comprehensive set of protein domain families automatically generated from the SWISSPROT and TrEMBL sequence databases. Mkdom2 is a ProDom program used to make ProDom family clusters. Protein domain families in ProDom were aligned using an improved parallelized program called Molecular Phylogenetics Karen Dowell 13 ProDomAlign, developed in C++ using OpenMP. ProDomAlign is based on MultAlign, a program well suited for aligning very large sequence families with thousands of associated sequences. As of early 2008, Pfam matched 72 percent of known proteins sequences, and 95 percent of proteins for which there is a known structure.Within the Pfam database, 75 percent of sequences will have one match to Pfam-A, 19 percent to Pfam-B. There are also two versions of Pfam-A and Pfam-B. Pfam-ls handles global alignments, and Pfam-fs is optimized for local alignments. Interestingly, Pfam entries can be classified as ââ¬Å"unknown,â⬠but that doesnââ¬â¢t mean the protein is undocumented. Unknown entries can be proteins for which some information is known, but it has not been fully researched or cannot be adequately annotated. For example, Pfam entry PFO1816 is a LeucineRich Repeat Variant (LRV), which has a known structure (1LRV ) available in the Protein Databank (pdb. rg). LRV repeat regions, which are found in many different proteins, are often involved in cell adhesion, DNA repair, and hormone receptionââ¬âbut identification of an LRV within a sequence encoding a protein doesnââ¬â¢t specifically reveal the proteinââ¬â¢s function. For studies involving a large number of protein searches, it may be more convenient to run Pfam locally on a client machine. The standalone Pfam system requires the HMMER2 software, the Pfam HMM libraries and a couple of additional files from the Pfam website to be installed on the client machine. HMMER is a freely distributable implementation of profile HMM software for protein sequence analysis. ) Once the initial search is complete, researchers can go to the Pfam website to further analyze select number of sequences using additional features on website. [6, 8, 24] TreeFam (TreeFam. org) TreeFam is a curated database of phylogenetic trees and orthology predictions f or all animal gene families that focuses on gene sets from animals with completely sequenced genomes. Orthologs and paralogs are inferred from phylogenetic tree of gene family.Release 4 contains curated trees for 1314 families and automatically generated trees for another 14351 families. [16, 23] Like Pfam, TreeFam is a two-part database: TreeFam-B contains automatically generated trees, and TreeFam-A consists of manually curated trees. To automatically generate trees, an algorithm selects clusters of genes to create TreeFam-B ââ¬Å"seedsâ⬠from core species with high-quality reference genome sequences, first using BLAST to rapidly assemble an initial list of possible matches, then HMMER to expand and filter probable sequence matches for each TreeFam B seed family.The filtered alignment is fed into a neighbor-joining algorithm and a tree is constructed based on amino acid mismatch distances. For TreeFam version 4, the most current release, five ââ¬Å"cleanâ⬠family trees were built for each TreeFam B seed, two using a maximum likelihood tree generated using PHYML (one based on the protein alignment, the other on codon alignment), three using a neighbor joining tree, using different distance measurements based on codon alignments. 16, 23] Scientific curators then manually any correct errors (based on information in the literature) in automatically generated TreeFam-B trees. Curated TreeFam-B trees then become seeds for TreeFam-A trees. Clean TreeFam-A trees are build using three merging algorithms and bootstrapping to find the consensus tree of seven trees: two constrained maximum likelihood trees based on protein and codon alignment, and five unconstrained neighbor-joining trees generated using different distance measurements based on codon alignments.For both TreeFam-B and TreeFam-A families, orthologs and paralogs are inferred only from clean trees using Duplication/Loss Inference (DLI) algorithm that requires a species tree (NCBI taxonomy tree). [16, 23] Molecular Phylogenetics PhyloFacts (phylogenomics. berkeley. edu/phylofacts) Karen Dowell 14 PhyloFacts is an online phylogenomic encyclopedia for protein functional and structural classification. It contains more than 57,000 ââ¬Å"booksâ⬠for protein superfamilies and structural domains.Each book contains heterogenous data for protein families, including multiple sequence alignments, one or more phylogenetic trees, predicted 3-D protein structures, predicted functional subfamilies, taxonomic distributions, GO annotations, and PFAM domains. HMMs constructed for each family and subfamily permit novel sequences to be classified to different functional classes. [14] Unlike other databases mentioned in this paper, PhyloFacts seeks to correct and clarify annotation errors associated with computational methods for predicting protein function based on sequence homology.It uses a consensus approach that integrates many different prediction methods and sources of experimental data over an evolutionary tree. By applying evolutionary and structural clustering of proteins, PhyloFacts is able to analyze disparate datasets using multiple methods, identify potential errors in database annotations, and provide a mechanism for improving the accuracy of functional annotation in general. [14] PhyloFacts can be used to search for protein structure prediction or functional classification for a particular protein sequence.Researchers may also browse through protein family books and multiple sequence alignments, phylogenetic trees, HMMs and other pertinent information for proteins of interest. This webservice also provides many links to literature and other information sources. [14] Applied Molecular Phylogenetics Molecular phylogenetic studies have many diverse applications. As the amount of publically available molecular sequence data grows and methods for modeling evolution become more sophisticated and accessible, more and more biologists are incorporating phylog enetic analyses into their research trategy. Hereââ¬â¢s a sampling of how molecular phylogenetics might be applied. Tracing the evolution of man In one case study, molecular phylogenetic techniques were used to compare and analyze variation in DNA sequences using modern human and Neanderthal mitochondrial DNA (mtDNA). For this study, 206 modern human mtDNAs and parts of two Neanderthal mtDNAs sequences derived from skeletal remains were used to generate an initial dataset. Genetic distance was first estimated using the Jukes-Cantor single parameter model.Then the Kimura 2-Parameter model was used to distinguish between transition (replacement of one purine with another purine or one pyrimidine with another pyrimidine) and transversion (replacement of one purine with a pyrimidine or vice versa) probabilities with Kimura 2parameter model. A phylogenetic tree representing primate evolution was generated using pairwise genetic distances between primate Hypervariable regions I and II of mtDNA. [3] Chasing an epidemic: SARS Using publically available genomic data, it is possible to reconstruct the progression of the SARS epidemic over time and geographically.To conduct this phylogenetic analysis, researchers used the neighborjoining method to construct a phylogenetic tree of spike proteins in various coronaviruses and identify the viral host (a Himalyan palm civet). They then obtained 13 SARs genome sequences with documented information on the date and location of the sample. The neighbor-joining method and a distance matrix based on Jukes-Cantor model, were used to generate an epidemic tree, from which it was possible to identify the origin (date and location) of the virus by observing progression of mutations over time. 3] Molecular Phylogenetics Barking up the right tree Karen Dowell 15 Phylogenetics is increasingly incorporated into biological and biomedical research papers. When the canine genome was published, researchers used sequence data to estimate a co mprehensive phylogeny of the canid family. Figure 15. Phylogenetic Tree of the Canid family This canid family phylogenetic tree is based on 15 kb of exon and intron sequence. It was constructed using the maximum parsimony method and represents the single most parsimonious tree.A good example of how phylogenies are referenced in the literature, this tree includes bootstrap values and Bayesian posterior probability values listed above and below internodes, respectively. Dashes indicate bootstrap values below 50%. In addition, divergence time in millions of years (Myr) is indicated for three nodes. [18] Seeing the Forest from the Trees Molecular phylogenetics is a broad, diverse field with many applications, supported by multiple computational and statistical methods. The sheer volumes of genomic data currently available (and rapidly growing) render molecular phylogenetics a key component of much biological research.Genome-scale studies on gene content, conserved gene order, gene expre ssion, regulatory networks, metabolic pathways, functional genome annotation can all be enriched by evolutionary studies based on phylogenetic statistical analyses. [19, 25 27] Molecular phylogenies have fast become an integral part of biological research, pharmaceutical drug design, and bioinformatics techniques for protein structure prediction and multiple sequence alignment. Although not all molecular biologists and bioinformaticians may be familiar with the techniques describedMolecular Phylogenetics Karen Dowell 16 in this paper, this is a rapidly growing and expanding field and there is ongoing need for novel algorithms to solve complex phylogeny reconstruction problems. References 1. Baldauf, SL (2003) ââ¬Å"Phylogeny for the faint of heart: a tutorial. â⬠Trends in Genetics, 19(6):345-351. 2. Brown, D, K Sjolander (2006) ââ¬Å"Functional Classification Using Phylogenomic Inference. â⬠PLos Computational Biology, 2(6):0479-0483. 3. Cristianini, N, and M Hahn (2007 ) Introduction to Computational Genomics: A Case Studies Approach.Cambridge University Press: Cambridge. 4. Durbin, R, S Eddy, A Krogh, G Mitchison (1998) Biological Sequence Analysis. Cambridge University Press: Cambridge. 5. Ewens, WJ, R Grant (2005) Statistical Methods in Bioinformatics. Springer Science and Business Media: New York. 6. Finn, RD, J Tate, J Mistry, PC Coggill, SJ Sammut, HR Hotz, G Ceric, K Forslund, SR Eddy, ELL Sonnhammer, A Bateman (2008) ââ¬Å"The Pfam protein families database. â⬠Nucleic Acids Research, 36:D281288. 7. Gabaldon, T (2008) ââ¬Å"Large-scale assignment of orthology: back to phylogenetics? Genome Biology, 9:235. 1-235. 6. 8. Gollery, M. (2008) Handbook of Hidden Markov Models in Bioinformatics. CRC Press, Taylor & Francis Group: London. 9. Goodstadt, L, CP Ponting (2006) ââ¬Å"Phylogenetic Reconstruction of Orthology, Paralogy, and Conserved Synteny for Dog and Human. â⬠PLoS Computational Biology, 2(9):1134-1150. 10. Hall, BG. (2004 ) Phylogenetic Trees Made Easy: A How-To Manual, 2nd ed. Sinauer Associates, Inc. : Sunderland, MA. 11. Hartwell, LH, L Hood, ML Goldberg, AE Reynolds, LM Silver, RC Veres (2008) Genetics: From Genes to Genomes, 3rd Ed.McGraw-Hill: New York. 12. Heinicke, S, MS Livstone, C Lu, R Oughtred, F Kang, SV Angiuoli, O White, D Botstein, K Dolinski (2007) ââ¬Å"The Princeton Protein Orthology Database (P-POD): A Comparative Genomics Analysis Tool for Biologists. â⬠PLoS ONE, 8:e766. 1-15. 13. Kortschak, RD, R Tamme (2001) ââ¬Å"Evolutionary analysis of vertebrate Notch genes. â⬠Dev Genes Evol, 211:350-354. 14. Krishnamurthy, N, DP Brown, D Kirshner, K Sjolander (2006) ââ¬Å"PhyloFacts: an online structural phylogenomic encyclopedia for protein functional and structural classification. â⬠Genome Biology, 7:R83. -13. 15. Kuzniar, A, RCHJ van Ham, S Pongor, JAM Leunissen (2008) ââ¬Å"The quest for orthologs: finding the corresponding gene across genomes. â⬠Trends in G enetics, 24(11):539-551. Molecular Phylogenetics Karen Dowell 17 16. Li, H, A Coghlan, J Ruan, LJ Coin, JK Heriche, L Osmotherly, R Li, T Liu, Z Zhang, L Bolund, GKS Wong, W Zheng, P Dehal, J Wang, R Durbin (2006) ââ¬Å"TreeFam: a curated database of phylgenetic trees of animal gene families. â⬠Nucleic Acids Research, 34:D573-580. 17. Li, WH (1997) Molecular Evolution. Sinauer Associates: Sunderland, MA. 18.Lindblad-Toh, K, CM Wade, TS Mikkelsen, EK Karlsson, DB Jaffe, M Kamal, M Clamp, JL Chang, EJ Kulbokas III, MC Zody, E Mauceli, X Xie, M Breen, RK Wayne, EA Ostrander, CP Ponting, F Galibert, DR Smith, PJ deJong, E Kirkness, P Alvarez, T Biagi, W Brockman, J Butler, C Chin, A Cook, J Cuff, MJ Daly, D DeCaprio, S Gnerre, M Grabherr, M Kellis, M Kleber, C Bardeleben, L Goodstadt, A Heger, C Hitte, L Kim, KP Koepfli, HG Parker, JP Pollinger, SMJ Searle, NB Sutter, R Thomas, C Webber, ES Lander (2005) ââ¬Å"Genome Sequence, Comparative Analysis and Haplotype Structure of the Domestic Dog.Nature, 438:803-819. 19. Linder, CR, T Warnow (2005) ââ¬Å"An overview of phylogeny reconstruction. â⬠In the Handbook of Computational Molecular Biology, Chapman and Hall/CRC Computer & Information Science. 20. Lio, P, N Goldman (1998) ââ¬Å"Models of Molecular Evolution and Phylogeny. â⬠Genome Research, 8:12331244. 21. Mi, H, N Guo, A Kejariwal, PD Thomas (2007) ââ¬Å"PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways. Nucleic Acids Research, 35:D247-252. 22. Patthy, Laszlo. (1999) Protein Evolution. Blackwell Science, Ltd: Malden, MA. 23. Ruan, J, H Li Z Chen, A Coghlan, LJM Coin, Y Guo, JK Heriche, Y Hu, K Kristiansen, R Li, T Liu, A Mose, J Qin, S Vang, AJ Vilella, A Ureta-Vidal, L Bolund, J Wang, R Durbin (2008) ââ¬Å"TreeFam: 2008 Update. â⬠Nucleic Acids Research, 36:D735-740. 24. Sammut, SJ, RD Finn, A Bateman (2008) ââ¬Å"Pfam 10 years on: 10000 families and still growing. â ⬠Briefings in Bioinformatics, 9(3):210-219. 5. Thomas, PD, A Kejariwal, N Guo, H Mi, MJ Campbell, A Muruganujan, B Lazareva-Ulitsky (2006) ââ¬Å"Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools. â⬠Nucleic Acids Research, 34:W645-650. 26. Thomas, PD, MJ Campbell, A Kejariwal, H Mi, B Karlak, R Daverman, K Diemer, A Muruganujan, A Narechania. ââ¬Å"PANTHER: A Library of Protein Families and Subfamilies Indexed by Function. â⬠Genome Research, 13:2129-2141. 27.Warnow, T (2004) ââ¬Å"Computational Methods in Phylogeneticsâ⬠Computational Systems Biology Conference, Stanford, CA 28. Whelan, S, P Lio, N Goldman (2001) ââ¬Å"Molecular phylogenetics: state of the art methods for looking into the past. â⬠Trends in Genetics, 17(5):262-272. Molecular Phylogenetics Karen Dowell 18 Appendix Website Resources Phylogeny Programs. A University of Washington site formerly supported by the National Science Foundation. http://www. evolution. genetics. washington. edu/phylip/software. tml TreeFam Tree Families Database. http://wwww. treefam. org Protein Analysis Through Evolutionary Relationships (PANTHER) Classification System. http://www. pantherdb. org. 29. Pfam Database of Protein Families. http://pfam. sanger. ac. uk 30. Princeton Protein Orthology Database (P-POD). http://ppod. princeton. edu 31. Wikipedia. http://en. wikipedia. org/wiki/Tree_of_life(science) Cover Page The cover image is from a phylogeny of canid species that appeared in Lindblad-Toh et al, 2005. [18]
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