HUMAN POPULATIONGENETICS

Foundations of Human Biology

Series Editors:Matt CartmillKaye BrownBoston University

The Growth of Humanity by Barry Bogin

Fundamentals of Forensic Anthropology by Linda L. Klepinger

The Human Lineage by Matt Cartmill and Fred H. Smith

HUMAN POPULATIONGENETICS

JOHN H. RELETHFORDDepartment of AnthropologyState University of New York College at Oneonta

A JOHN WILEY & SONS, INC., PUBLICATION

Copyright © 2012 by Wiley-Blackwell. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished 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 ofhuman populations. The purpose of this book is to provide a basic background text for advancedundergraduate and graduate students interesting in the mechanisms of humanmicroevolution’’—Provided by publisher.

ISBN 978-0-470-46467-0 (pbk.)1. Human population genetics. I. Title.

GN289.R45 2012599.93’5—dc23

2011028962

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

CONTENTS

Foreword vii

Preface ix

1 GENETIC, MATHEMATICAL, AND ANTHROPOLOGICALBACKGROUND 1I. The Scope of Population Genetics 2II. Genetics Background 5III. Principles of Probability 14IV. The Anthropological Connection 17V. A Closing Thought 21

2 HARDY–WEINBERG EQUILIBRIUM 23I. Genotype and Allele Frequencies 24II. What is Hardy–Weinberg Equilibrium? 30III. The Mathematics of Hardy–Weinberg Equilibrium 31IV. Using Hardy–Weinberg Equilibrium 37V. Extensions of Hardy–Weinberg Equilibrium 40VI. Hardy–Weinberg Equilibrium and Evolution 44VII. Summary 45

3 INBREEDING 49I. Quantifying Inbreeding 51II. Population Genetics and Inbreeding 62III. Inbreeding in Human Populations 65IV. Summary 75

4 MUTATION 77I. The Nature of Mutations 77II. Models of Mutation 81III. Mutational History and Anthropological Questions 88IV. Summary 96

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5 GENETIC DRIFT 101I. What is Genetic Drift? 102II. Genetic Drift and Population Size 112III. Effects on Genetic Variation 120IV. Mutation and Genetic Drift 121V. Coalescent Theory 125VI. Summary 131

6 MODELS OF NATURAL SELECTION 139I. How Does Natural Selection Work? 140II. A General Model of Natural Selection 145III. Types of Natural Selection 147IV. Other Aspects of Selection 160V. Summary 167

7 NATURAL SELECTION IN HUMAN POPULATIONS 181I. Case Studies of Natural Selection in Human Populations 182II. Are Humans Still Evolving? 198III. Summary 203

8 GENE FLOW 205I. The Evolutionary Impact of Gene Flow 206II. Models of Gene Flow 208III. Gene Flow and Genetic Drift 213IV. Estimating Admixture in Human Populations 226V. Summary 230

9 HUMAN POPULATION STRUCTURE AND HISTORY 237I. Case Studies of Human Population Structure 238II. The Origin of Modern Humans 242III. Case Studies of Population Origins 247IV. Summary 255

Glossary 257

References 267

Index 279

FOREWORD

If, like us, you find yourself hard-pressed to follow the fast-paced scrimmagesof anthropological genetics from the sidelines, this is the book you have beenwaiting for. John Relethford, one of the world’s leading contributors to thesedebates, has written it to engage all of us in this important and rapidly evolvingarea of scientific inquiry. In Human Population Genetics, he leads us through classicstudies and current debates in an easy, clear, informal style that draws us in andinvolves us in the action and arguments. Relethford’s passion for understandingthe genetics of human populations, and his low-stress approach to what can be adifficult and esoteric topic, kindle a like passion in the reader and make this bookthat rare thing among textbooks—a source of excitement and inspiration.

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

Throughout this book, Relethford systematically preaches and teaches a scien-tific 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 notfit’’) in a way that always solicits involvement by the reader (‘‘To see this, letus try an example’’). In every topic he presents, he returns to the readers’ pointof view (‘‘What effect do you think selection has had on the allele frequencies?’’) andincludes them in the developing narrative. His readers will learn the conceptsthat are crucial to all fields of population biology by studying examples of specialrelevance to biological anthropology—how familiarity with genetic evidence can

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viii FOREWORD

inform us of our history (see the rich discussion on tracking the appearance of theCCR5-�32 allele and subsequent resistance to the AIDS virus), how adaptation hastaken many different paths in human history (see the discussion on different high-altitude adaptations in Tibetan and Andean people), and how cultural behaviorimpacts genetic processes (see the discussion on agriculture and hemoglobin S).‘‘Instead of cultural evolution negating genetic evolution,’’ he writes, ‘‘we arefinding evidence of how cultural change has accelerated genetic evolution.’’

That sentence, and the evidence behind it, would by itself make HumanPopulation Genetics worth having on your bookshelf. Every chapter of the booksparkles 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 mostimportant and exciting scientific conversations of our day. If you are a student ofbiological anthropology at any level, or a scientist or educator who teaches thesesubjects, you will find his new book an invaluable source of novel insights and freshillumination of key ideas. We are proud and delighted to see Human PopulationGenetics added to the Wiley–Blackwell series of textbooks on the foundations ofhuman biology.

Kaye BrownMatt Cartmill

PREFACE

WHAT ARE WE DOING HERE?

This book is about the intersection of mathematics, biology, and anthropology. Assuch, it has two basic goals. First, the book provides an introduction to the study ofpopulation genetics, which provides the mathematical basis of evolutionary theoryby describing changes in the frequency of genetic variants from one generationto the next. Second, this introduction has been designed for specific applicationto human populations. Although population genetics is a field that applies toall organisms, the focus throughout this book, particularly in case studies, is onhuman populations. As an anthropologist, my interest is by definition primarilyon human populations and genetic diversity. Not that this book has no utilityoutside of human populations—far from it. I have designed this book to providea simple introduction to population genetics with minimal mathematics that canbe used by advanced undergraduate and graduate students in a variety of fields,including anthropology, biology, and ecology. If you are using this book in oneof those other disciplines, rest assured that the same basic principles presentedhere are applicable to organisms, and your instructor will likely provide other,nonhuman, case studies for clarification. You need not have a detailed backgroundin genetics, although this book is intended for students that have had some initialgrounding in genetics, such as one would obtain from an introductory course inbiological anthropology or biology.

FORMAT AND ORGANIZATION OF THE BOOK

A quick look through the pages of this book will reveal a number of formulas. Thismay seem intimidating, but it is not. Although some elementary mathematics isneeded to understand population genetics, we do not have to use very advancedmath to learn the basics. Throughout this book, we will use only simple algebraof the type that you likely learned in middle or senior high school and some basicconcepts of probability, which are developed in the text as we proceed. I alsouse additional ways, beyond equations, to present the material. Although it is awonderful experience to glance at a mathematical formula and gain immediateinsight into what that formula says about reality, it is (at least for me) a rare

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experience. I usually have to look at a graphic representation of the formula orutilize an analogy to understand the underlying ideas. Thus, this text uses a lot ofgraphs and analogies to make the basic points and help you relate the evolutionaryprocess to mathematical ideas.

As with any field, population genetics has its own set of terms. Anythingspecific to genetics or population genetics is defined in the text, with an additionalglossary at the end of the book collecting all such terms. All glossary terms aremarked in boldface in the text the first time they appear. In-text citation is usedin 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 amalso very grateful for the guidance and advice of my editor, Karen Chambers. Shewas a delight to work with on this project. Thanks also to Anna Ehler, EditorialAssistant, and Rosalyn Farkas, Production Editor, for all of their help and attentionto my constant questions.

I was first introduced to the study of population genetics in 1975 when I metmy graduate school advisor, Frances Lees. I owe Frank a lot for his guidance andfriendship over the years in addition to his patience at teaching me populationgenetics. He got me started both in my profession and in this particular field. Iam also very grateful to his academic advisor, Michael Crawford, for helping melearn even more about population genetics over the course of several decades offriendship 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 HenryHarpending. My work with them has been a high point of my career.

Looking back, I can identify many friends and colleagues over the years withwhom I have shared discussions at some level or another on population genetics.Some of these have been coauthors, and others have been colleagues with similarinterests who have shared one or many conversations or emails. They all havecontributed 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 apologiesif I have missed anyone): Guido Barbujani, Deborah Bolnick, the late EllenBrennan, 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, AndreaManica, Yoshiro Matsuo, Jim Mielke, Andy Merriwether, John Mitchell, KariNorth, Carolyn Olsen, Esteban Parra, Alan Rogers, Charles Roseman, DennisO’Rourke, Lisa Sattenspiel, Michael Schillaci, Tad Schurr, Steve Sherry, PeterSmouse, Bob Sokal, Dawnie Steadman, Anne Stone, Mark Stoneking, AlanSwedlund, Alan Templeton, Forrest Tierson, John VandeBerg, Noreen von

PREFACE xi

Cramon-Taubadel, Tim Weaver, Ken Weiss, Dick Wilkinson, Sarah Williams-Blangero, Milford Wolpoff and Jim Wood. Special thanks to Alan Bittles forproviding me with references on inbreeding. I also acknowledge my debt tothree individuals whom I have never met, but have spent many hours studyingtheir insightful writings: Luca Cavalli-Sforza, Newton Morton, and the lateSewall Wright.

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

John H. RelethfordState University of New York

C H A P T E R 1GENETIC, MATHEMATICAL,AND ANTHROPOLOGICALBACKGROUND

My interest in human population genetics started with my difficulty in picking amajor 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 math-ematics. Each of these fields appealed to me in some ways initially, but nonesufficiently to take the 10 or more courses to complete an academic major. As Ishifted almost daily in my search for a major, I stumbled across anthropology, adiscipline that is characterized by academic breadth across the liberal arts. In theUnited States, anthropology departments are most often constructed around thefour-field approach championed by the famous early twentieth-century anthro-pologist, Franz Boas. Here, anthropology is divided into four subfields: (1) culturalanthropology, which examines behaviors in current and recent human populations;(2) archaeology, which reconstructs cultural behavior in prehistoric and historichuman societies; (3) linguistics, the study of language, a uniquely human formof communicating culture; and (4) biological anthropology (also known as physicalanthropology), which focuses on the biological evolution and variation of the humanspecies.

With its focus on both cultural and biological aspects of humanity, and itsconcern with natural science, social science, and the humanities, anthropologyproved to be the perfect liberal arts major for someone like me, who had a difficulttime picking any single major. Over time, however, I found myself gravitatingmore toward the subfield of biological anthropology as I became fascinatedby the ways in which humanity had evolved. As I entered graduate school,I wound up concentrating more and more on the nature of human biologicalvariation, and questions about our species’ biological diversity. How are humanpopulations similar to and different from each other biologically? How do thesedifferences relate to the process of evolution, and how do these processes relateto human history, culture, and the environment? In one form or another, these

Human Population Genetics, First Edition. John H. Relethford.© 2012 Wiley-Blackwell. Published 2012 by John Wiley & Sons, Inc.

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