Human Population Genetics E-Book

John H. Relethford

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Serie: Foundation of Human Biology
• Sprache: Englisch

Seitenzahl: 611

Veröffentlichungsjahr: 2012

Beschreibung

Introductory guide to human population genetics and microevolutionary theory

Providing an introduction to mathematical population genetics, Human Population Genetics gives basic background on the mechanisms of human microevolution. This text combines mathematics, biology, and anthropology and is best suited for advanced undergraduate and graduate study.

Thorough and accessible, Human Population Genetics presents concepts and methods of population genetics specific to human population study, utilizing uncomplicated mathematics like high school algebra and basic concepts of probability to explain theories central to the field. By describing changes in the frequency of genetic variants from one generation to the next, this book hones in on the mathematical basis of evolutionary theory.

Human Population Genetics includes:

• Helpful formulae for learning ease

• Graphs and analogies that make basic points and relate the evolutionary process to mathematical ideas

• Glossary terms marked in boldface within the book the first time they appear

• In-text citations that act as reference points for further research

• Exemplary case studies

• Topics such as Hardy-Weinberg equilibrium, inbreeding, mutation, genetic drift, natural selection, and gene flow

Human Population Genetics solidifies knowledge learned in introductory biological anthropology or biology courses and makes it applicable to genetic study.

NOTE: errata for the first edition can be found at the author's website: http://employees.oneonta.edu/relethjh/HPG/errata.pdf

Leseprobe

Table of Contents

Series Page

Title Page

Copyright

Foreword

Preface

What are We Doing Here?

Format and Organization of the Book

Acknowledgments

Chapter 1: Genetic, Mathematical, and Anthropological Background

1.1 The Scope of Population Genetics

1.2 Genetics Background

1.3 Principles of Probability

1.4 The Anthropological Connection

1.5 A Closing Thought

Chapter 2: Hardy–Weinberg Equilibrium

2.1 Genotype And Allele Frequencies

2.2 What is Hardy–Weinberg Equilibrium?

2.3 The Mathematics of Hardy–Weinberg Equilibrium

2.4 Using Hardy–Weinberg Equilibrium

2.5 Extensions of Hardy–Weinberg Equilibrium

2.6 Hardy–Weinberg Equilibrium and Evolution

2.7 Summary

Appendix 2.1 Proof Showing How Allele Frequencies can be Computed from Genotype Frequencies

Appendix 2.2 Using the Chi-Square Statistic to Test for Hardy–Weinberg Equilibrium

Chapter 3: Inbreeding

3.1 Quantifying Inbreeding

3.2 Population Genetics and Inbreeding

3.3 Inbreeding in Human Populations

3.4 Summary

Chapter 4: Mutation

4.1 The Nature of Mutations

4.2 Models of Mutation

4.3 Mutational History and Anthropological Questions

4.4 Summary

Appendix 4.1 Use of A Recurrence Relation to Solve Iterative Equations

Chapter 5: Genetic Drift

5.1 What is Genetic Drift?

5.2 Genetic Drift and Population Size

5.3 Effects on Genetic Variation

5.4 Mutation and Genetic Drift

5.5 Coalescent Theory

5.6 Summary

Appendix 5.1 Decay of Heterozygosity Over Time Due to Genetic Drift

Appendix 5.2 Expected Heterozygosity at Equilibrium in the Infinite Alleles Model

Appendix 5.3 Computation of Nucleotide Diversity

Chapter 6: Models of Natural Selection

6.1 How Does Natural Selection Work?

6.2 A General Model of Natural Selection

6.3 Types of Natural Selection

6.4 Other Aspects of Selection

6.5 Summary

Appendix 6.1 Derivation of the Amount of Change in Allele Frequencies per Generation ( and ) for A General Model of Natural Selection

Appendix 6.2 Derivation of Formulas for Selection against the Recessive Homozygote

Appendix 6.3 Derivation of Formulas for Selection Against Dominant Alleles

Appendix 6.4 Derivation of Formulas for Selection with Codominant Alleles

Appendix 6.5 Derivation of Formulas for Selection Against the Heterozygote

Appendix 6.6 Derivation of Formulas for Selection for the Heterozygote

Appendix 6.7 Calculus-Based Derivation of the Equilibrium Allele Frequency under Selection for the Heterozygote

Appendix 6.8 Mutation–Selection Equilibrium under Selection Against A Recessive Allele

Appendix 6.9 Mutation–Selection Equilibrium under Selection Against A Dominant Allele

Chapter 7: Natural Selection In Human Populations

7.1 Case Studies of Natural Selection in Human Populations

7.2 Are Humans Still Evolving?

7.3 Summary

Chapter 8: Gene Flow

8.1 The Evolutionary Impact of Gene Flow

8.2 Models of Gene Flow

8.3 Gene Flow and Genetic Drift

8.4 Estimating Admixture in Human Populations

8.5 Summary

Appendix 8.1 Changes in Allele Frequency Over Time in an Island Model

Appendix 8.2 Genetic Similarity: The R Matrix

Appendix 8.3 Genetic Similarity: Nei'S Genetic Identity

Appendix 8.4 Relationship Between per Generation Admixture (m) and Accumulated Admixture (M)

Chapter 9: Human Population Structure and History

9.1 Case Studies of Human Population Structure

9.2 The Origin of Modern Humans

9.3 Case Studies of Population Origins

9.4 Summary

Glossary

References

Index

For further information visit: the book web page http://www.openmodelica.org, the Modelica Association web page http://www.modelica.org, the authors research page http://www.ida.liu.se/labs/pelab/modelica, or home page http://www.ida.liu.se/~petfr/, or email the author at [email protected]. Certain material from the Modelica Tutorial and the Modelica Language Specification available at http://www.modelica.org has been reproduced in this book with permission from the Modelica Association under the Modelica License 2 Copyright © 1998–2011, Modelica Association, see the license conditions (including the disclaimer of warranty) at http://www.modelica.org/modelica-legal-documents/ModelicaLicense2.html. Licensed by Modelica Association under the Modelica License 2.

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Copyright © 2011 by the Institute of Electrical and Electronics Engineers, Inc.

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Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Relethford, John.

Human population genetics / John H. Relethford.

p. cm.

Includes index.

Summary: ``Human Population Genetics will provide an introduction to mathematical population genetics, along with relevant examples from human (and some non-human primate) populations, and will also present concepts and methods of population genetics that are specific to the study of human populations. The purpose of this book is to provide a basic background text for advanced undergraduate and graduate students interesting in the mechanisms of human microevolution''–Provided by publisher.

ISBN 978-0-470-46467-0 (pbk.)

1. Human population genetics. I. Title.

GN289.R45 2012

599.93'5–dc23

2011028962

Foreword

If, like us, you find yourself hard-pressed to follow the fast-paced scrimmages of anthropological genetics from the sidelines, this is the book you have been waiting for. John Relethford, one of the world's leading contributors to these debates, has written it to engage all of us in this important and rapidly evolving area of scientific inquiry. In Human Population Genetics, he leads us through classic studies and current debates in an easy, clear, informal style that draws us in and involves us in the action and arguments. Relethford's passion for understanding the genetics of human populations, and his low-stress approach to what can be a difficult and esoteric topic, kindle a like passion in the reader and make this book that rare thing among textbooks—a source of excitement and inspiration.

Population genetics and statistical theory were born as conjoined twins in the monumental work of R. A. Fisher in the 1920s, which transformed evolutionary biology into a full-fledged science capable of making and testing predictions with numbers in them. But many people who are eager to learn about human biology and evolution are turned off by the statistical foundations of evolutionary theory. Almost everyone who teaches the fundamentals of our science has learned to dread the dazed expressions that come over students' faces the moment the Hardy–Weinberg equation hits the screen. Relethford shows us, and them, how to get around this stumbling block. Drawing the reader effortlessly in through plain and simple examples beautifully chosen to clarify the mathematics of probability, Relethford recruits his mastery of the subject and his skill as a teacher and writer to present the math in a user-friendly way that displaces the hard work of deriving formulas into adjacent appendices. His readers first master the essentials and later reward themselves by seeing the mathematics underlying the simple models they have just grasped. This process of orderly presentation leaves readers self-confident and ready to take on ever more complex material.

Throughout this book, Relethford systematically preaches and teaches a scientific approach to knowledge (“Much of science consists of developing a simple model, testing its fit in the real world, and then explaining why and how it fits and does not fit”) in a way that always solicits involvement by the reader (“To see this, let us try an example”). In every topic he presents, he returns to the readers' point of view (“What effect do you think selection has had on the allele frequencies?”) and includes them in the developing narrative. His readers will learn the concepts that are crucial to all fields of population biology by studying examples of special relevance to biological anthropology—how familiarity with genetic evidence can inform us of our history (see the rich discussion on tracking the appearance of the CCR5-Δ32 allele and subsequent resistance to the AIDS virus), how adaptation has taken many different paths in human history (see the discussion on different high-altitude adaptations in Tibetan and Andean people), and how cultural behavior impacts genetic processes (see the discussion on agriculture and hemoglobin S). “Instead of cultural evolution negating genetic evolution,” he writes, “we are finding evidence of how cultural change has accelerated genetic evolution.”

That sentence, and the evidence behind it, would by itself make Human Population Genetics worth having on your bookshelf. Every chapter of the book sparkles with conclusions that are just as simple, straightforward, and far-reaching. All of its readers can rely on John Relethford to lead them into some of the most important and exciting scientific conversations of our day. If you are a student of biological anthropology at any level, or a scientist or educator who teaches these subjects, you will find his new book an invaluable source of novel insights and fresh illumination of key ideas. We are proud and delighted to see Human Population Genetics added to the Wiley–Blackwell series of textbooks on the foundations of human biology.

Kaye Brown

Matt Cartmill

Preface

What are We Doing Here?

This book is about the intersection of mathematics, biology, and anthropology. As such, it has two basic goals. First, the book provides an introduction to the study of population genetics, which provides the mathematical basis of evolutionary theory by describing changes in the frequency of genetic variants from one generation to the next. Second, this introduction has been designed for specific application to human populations. Although population genetics is a field that applies to all organisms, the focus throughout this book, particularly in case studies, is on human populations. As an anthropologist, my interest is by definition primarily on human populations and genetic diversity. Not that this book has no utility outside of human populations—far from it. I have designed this book to provide a simple introduction to population genetics with minimal mathematics that can be used by advanced undergraduate and graduate students in a variety of fields, including anthropology, biology, and ecology. If you are using this book in one of those other disciplines, rest assured that the same basic principles presented here are applicable to organisms, and your instructor will likely provide other, nonhuman, case studies for clarification. You need not have a detailed background in genetics, although this book is intended for students that have had some initial grounding in genetics, such as one would obtain from an introductory course in biological anthropology or biology.

Format and Organization of the Book

A quick look through the pages of this book will reveal a number of formulas. This may seem intimidating, but it is not. Although some elementary mathematics is needed to understand population genetics, we do not have to use very advanced math to learn the basics. Throughout this book, we will use only simple algebra of the type that you likely learned in middle or senior high school and some basic concepts of probability, which are developed in the text as we proceed. I also use additional ways, beyond equations, to present the material. Although it is a wonderful experience to glance at a mathematical formula and gain immediate insight into what that formula says about reality, it is (at least for me) a rare experience. I usually have to look at a graphic representation of the formula or utilize an analogy to understand the underlying ideas. Thus, this text uses a lot of graphs and analogies to make the basic points and help you relate the evolutionary process to mathematical ideas.

As with any field, population genetics has its own set of terms. Anything specific to genetics or population genetics is defined in the text, with an additional glossary at the end of the book collecting all such terms. All glossary terms are marked in boldface in the text the first time they appear. In-text citation is used in this text, where specific citations are references by author(s) name(s) and year, such as “Relethford (2004).”

Acknowledgments

I owe much thanks to Matt Cartmill and Kaye Brown, series editors of the Wiley-Blackwell Foundation of Human Biology series, for inviting me to write this book, and for their careful analysis and discussion of the book's goals and structure. I am also very grateful for the guidance and advice of my editor, Karen Chambers. She was a delight to work with on this project. Thanks also to Anna Ehler, Editorial Assistant, and Rosalyn Farkas, Production Editor, for all of their help and attention to my constant questions.

I was first introduced to the study of population genetics in 1975 when I met my graduate school advisor, Frances Lees. I owe Frank a lot for his guidance and friendship over the years in addition to his patience at teaching me population genetics. He got me started both in my profession and in this particular field. I am also very grateful to his academic advisor, Michael Crawford, for helping me learn even more about population genetics over the course of several decades of friendship and collaboration on research projects.

I have worked with other colleagues on research in human population genetics. Two of these colleagues stand out in particular—John Blangero and Henry Harpending. My work with them has been a high point of my career.

Looking back, I can identify many friends and colleagues over the years with whom I have shared discussions at some level or another on population genetics. Some of these have been coauthors, and others have been colleagues with similar interests who have shared one or many conversations or emails. They all have contributed to my understanding of human population genetics. Needless to say, my errors are mine and mine alone. This is the list (and my most sincere apologies if I have missed anyone): Guido Barbujani, Deborah Bolnick, the late Ellen Brennan, Ranajit Chakraborty, Ric Devor, Ravi Duggarali, Elise Eller, Alan Fix, Jon Friedlaender, Rosalind Harding, Mike Hammer, John Hawks, Jeff Heilveil, Keith Hunley, Cashell Jaquish, Lynn Jorde, Lyle Konigsberg, Tibor Koertvelyessy, Ken Korey, the late Gabe Lasker, Paul Leslie, Jeff Long, Lorena Madrigal, Andrea Manica, Yoshiro Matsuo, Jim Mielke, Andy Merriwether, John Mitchell, Kari North, Carolyn Olsen, Esteban Parra, Alan Rogers, Charles Roseman, Dennis O'Rourke, Lisa Sattenspiel, Michael Schillaci, Tad Schurr, Steve Sherry, Peter Smouse, Bob Sokal, Dawnie Steadman, Anne Stone, Mark Stoneking, Alan Swedlund, Alan Templeton, Forrest Tierson, John VandeBerg, Noreen von Cramon-Taubadel, Tim Weaver, Ken Weiss, Dick Wilkinson, Sarah Williams-Blangero, Milford Wolpoff and Jim Wood. Special thanks to Alan Bittles for providing me with references on inbreeding. I also acknowledge my debt to three individuals whom I have never met, but have spent many hours studying their insightful writings: Luca Cavalli-Sforza, Newton Morton, and the late Sewall Wright.

Last, but certainly not least, I dedicate this book to the five people who mean the most to me in the world—my wife, Hollie Jaffe; my sons, David, Ben, and Zane; and my mother-in-law, Terry Adler. Thanks to all for putting up with me and loving me.

John H. Relethford

State University of New York

Chapter 1

Genetic, Mathematical, and Anthropological Background

My interest in human population genetics started with my difficulty in picking a major in college.

As is often the case, my interests as an undergraduate student were varied, including fields as different as sociology, biology, geography, history, and mathematics. Each of these fields appealed to me in some ways initially, but none sufficiently to take the 10 or more courses to complete an academic major. As I shifted almost daily in my search for a major, I stumbled across anthropology, a discipline that is characterized by academic breadth across the liberal arts. In the United States, anthropology departments are most often constructed around the four-field approach championed by the famous early twentieth-century anthropologist, Franz Boas. Here, anthropology is divided into four subfields: (1) cultural anthropology, which examines behaviors in current and recent human populations; (2) archaeology, which reconstructs cultural behavior in prehistoric and historic human societies; (3) linguistics, the study of language, a uniquely human form of communicating culture; and (4) biological anthropology (also known as physical anthropology), which focuses on the biological evolution and variation of the human species.

With its focus on both cultural and biological aspects of humanity, and its concern with natural science, social science, and the humanities, anthropology proved to be the perfect liberal arts major for someone like me, who had a difficult time picking any single major. Over time, however, I found myself gravitating more toward the subfield of biological anthropology as I became fascinated by the ways in which humanity had evolved. As I entered graduate school, I wound up concentrating more and more on the nature of human biological variation, and questions about our species' biological diversity. How are human populations similar to and different from each other biologically? How do these differences relate to the process of evolution, and how do these processes relate to human history, culture, and the environment? In one form or another, these questions have been at the root of many of the research topics I have focused on during my career, ranging from the effect of historical invasions on genetic diversity in Ireland, to changing patterns of marriage and migration in colonial Massachusetts, to the effect of history and geography on cranial shape across the world.

Underlying all of these questions is the subject of this book, human population genetics, which is a field that has the same breadth of topics that guided my search for a college major. Although this book focuses on human population genetics, it is important to realize that population genetics is a subject that concerns all organisms. Much of this book consists in explaining basic principles of population genetics, applicable to many species, with further illustration describing case studies from human populations. If you are reading this book in a course on general population genetics, as is often taught in biology departments, for example, you are likely to encounter further case studies on a variety of other species.

1.1 The Scope of Population Genetics

Before getting too far into the application of population genetics to the human species, it is useful to answer the basic question “What is population genetics?” This question can be answered by considering the nature of the broader field of genetics, the study of heredity in organisms. Genetics can be studied at various levels. The study of molecular genetics deals with the biochemical nature of heredity, specifically DNA and RNA. At this level, geneticists focus on the biochemical nature of heredity, including the structure and function of genes and other DNA sequences.

The study of Mendelian genetics, named after the Austrian monk, Gregor Mendel (1822–1884), is concerned with the process and pattern of genetic inheritance from parents to offspring. Mendel's work gave us a basic understanding of how inheritance works, and how discrete units of inheritance combine to produce genotypes and phenotypes. Whereas the focus of molecular genetics is on the transmission of information from cell to cell, Mendelian genetics focuses on the transmission of genetic information from one individual (a parent) to another (the offspring). Mendelian genetics is in essence a statistical subject, dealing with the probability of different genotypes and phenotypes in offspring. A classic example concerns two parents, each of which carries one copy of a recessive gene. The principles of probability show that the chance of any given offspring having copies of that gene, one from each parent, is . These principles will be reviewed later, but for now, you should just consider that the transmission of genetic information is subject to the laws of probability.