African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping

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.

Figure 1

A map of African language family distributions and hypothesized migration events within and out of Africa. African languages have been classified into four major language families: Niger-Kordofanian (spoken predominantly by agriculturalist populations across a broad geographic distribution in Africa), Afro-Asiatic (spoken predominantly by northern and eastern Africa pastoralists and agropastoralists), Nilo-Saharan (spoken predominantly by eastern and central African pastoralists), and Khoisan (a language containing click-consonants, spoken by southern and eastern African hunter-gatherer populations). Also plotted are the geographic origins of African samples included in the Center d’Etude du Polymorphisme Humain (CEPH) Human Genome Diversity Panel (CEPH-HGDP). Diagram adapted from Reference .

Figure 2

Ancestral Africans have maintained a large and subdivided population structure and have experienced complex patterns of population expansions, contractions, migration, and admixture during their evolutionary history. The bottleneck associated with the founding of non-African populations (~50–100 kya) resulted in lower levels of genetic diversity, an increase in linkage disequilibrium (LD), and more similar patterns of LD. In addition, several recent studies have suggested that a serial founder model of migration occurred in the history of non-Africans in which the geographic expansion of these populations occurred in many small steps, and each migration involved a sampling of variation from the previous population (36, 90, 109, 167). Solid horizontal lines indicate gene flow between populations and the dashed horizontal line indicates recent gene flow from Asia to Australia/Melanesia.

Figure 3

Several analyses have indicated that haplotype blocks [where single nucleotide polymorphisms (SNPs) are in strong linkage disequilibrium (LD)] extend over greater genomic distances and are more uniform in non-Africans compared to African populations. Additionally, the size and location of haplotype blocks can vary among African samples owing to the distinct demographic histories of populations from different geographic regions in Africa. The blue bars represent haplotype blocks and the thin orange bars denote regions of recombination. Vertical lines indicate SNPs and vertical arrows indicate haplotype tag SNPs (htSNPs). Because haplotype blocks are more variable in Africans compared to non-Africans, identification of htSNPs in diverse African ethnic groups and more dense tag htSNP coverage are needed to detect an association between marker(s) and disease loci in association studies.