Annu Rev Genom Human Genet 2008 9 403 433 Downloaded from arjournals annualreviews org by University of South Carolina Columbia on 04 05 10 For personal use only ANNUAL REVIEWS Further Click here for quick links to Annual Reviews content online including Other articles in this volume Top cited articles Top downloaded articles Our comprehensive search African Genetic Diversity Implications for Human Demographic History Modern Human Origins and Complex Disease Mapping Michael C Campbell1 and Sarah A Tishkoff 1 2 1 Department of Genetics University of Pennsylvania School of Medicine Philadelphia Pennsylvania 19107 email mcam mail med upenn edu 2 Department of Biology University of Pennsylvania School of Arts and Sciences Philadelphia Pennsylvania 19104 email tishkoff mail med upenn edu Annu Rev Genomics Hum Genet 2008 9 403 33 Key Words First published online as a Review in Advance on July 1 2008 disease susceptibility African populations genetic variation human evolution linkage disequilibrium The Annual Review of Genomics and Human Genetics is online at genom annualreviews org This article s doi 10 1146 annurev genom 9 081307 164258 c 2008 by Annual Reviews Copyright All rights reserved 1527 8204 08 0922 0403 20 00 Abstract Comparative studies of ethnically diverse human populations particularly in Africa are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease African populations are characterized by greater levels of genetic diversity extensive population substructure and less linkage disequilibrium LD among loci compared to non African populations Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets as well as exposure to infectious disease This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations as well as their implications for the mapping of complex traits including disease susceptibility 403 INTRODUCTION Annu Rev Genom Human Genet 2008 9 403 433 Downloaded from arjournals annualreviews org by University of South Carolina Columbia on 04 05 10 For personal use only One of the grand challenges of the postgenome era is to develop a detailed understanding of the heritable variation in the human genome 34 By characterizing genetic variation among individuals and populations we may gain a better understanding of differential susceptibility to disease differential response to pharmacological agents human evolutionary history and the complex interaction of genetic and environmental factors in producing phenotypes Africa is an important region to study human genetic diversity because of its complex population history and the dramatic variation in climate diet and exposure to infectious disease which result in high levels of genetic and phenotypic variation in African populations A better understanding of levels and patterns of variation in African genomes together with phenotype data on variable traits including susceptibility to disease and drug response will be critical for reconstructing modern human origins the genetic basis of adaptation to diverse environments and the development of more effective vaccines and other therapeutic treatments for disease This information will also be important for identifying variants that play a role in susceptibility to a number of complex diseases in people of recent African ancestry 170 185 204 HUMAN EVOLUTIONARY HISTORY IN AFRICA Africa is a region of considerable genetic linguistic cultural and phenotypic diversity There are more than 2000 distinct ethnolinguistic groups in Africa speaking languages that constitute nearly a third of the world s languages http www ethnologue com Figure 1 These populations practice a wide range of subsistence patterns including various modes of agriculture pastoralism and hunting gathering Africans also live in climates that range from the world s largest desert and second largest tropical rainforest to savanna swamps and mountain highlands and 404 Campbell Tishkoff these climates have in some cases undergone dramatic changes in the recent past 103 170 According to the Out of Africa OOA model of modern human origins anatomically modern humans originated in Africa and then spread across the rest of the globe within the past 100 000 years 202 The transition to modern humans within Africa was not sudden rather the paleobiological record indicates an irregular mosaic of modern archaic and regional morphological and behavioral traits that occurred over a substantial period of time and across a broad geographic range within Africa 124 The earliest known derived suite of morphological traits associated with modern humans appears in fossil remains from Ethiopia dated to 150 190 kya 125 224 However this nding does not rule out the existence of modern morphological traits in other regions of Africa before 100 kya particularly where specimens may be less well preserved and or where extensive archaeological and paleobiological investigations have not been conducted 170 Indeed a multiregional origin model for modern humans within Africa is not as unlikely as it would be for global populations considering the greater potential for migration and admixture within a single continental region 170 237 A more fully modern suite of traits appears in East Africa and Southwest Asia around 90 kya followed by a rapid spread of modern humans throughout the rest of Africa and Eurasia within the past 40 000 80 000 years 117 170 Figure 2 Two migration routes of modern humans out of Africa have been proposed The presence of modern humans in Oceania as early as 50 kya 63 64 which predates their presence in Europe 40 kya has suggested a southern coastal route around the Indian Ocean in which modern humans rst left Africa possibly via Ethiopia by crossing the Bab el Mandeb strait at the mouth of the Red Sea and then rapidly migrated to Southeast Asia and Oceania 61 170 Figure 1 This migration model is supported by the presence of very old mtDNA haplotypes in South Asia and their absence in the Levant 117 166 194 Other models European Northern route Selected migrations Historic migrations Prehistoric migrations Out of Africa migrations Arab Be uw a Semetic Sh Maures New World slave trade ja Southern route Fulani Fulbe Language families Afro Asiatic Nilo Saharan Khoisan Niger Kordofanian CEPH HGDP NIlo Saharan Ubangi Cushitic Annu Rev Genom
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