Evidence from Cameroon reveals differences in the genetic structure and histories of chimpanzee populations

The history of the genus Pan is a topic of enduring interest. Chimpanzees (Pan troglodytes) are often divided into subspecies, but the population structure and genetic history of chimpanzees across Africa remain unclear. Some population genetics studies have led to speculation that, until recently, this species constituted a single population with ongoing gene flow across its range, which resulted in a continuous gradient of allele frequencies. Chimpanzees, designated here as P. t. ellioti, occupy the Gulf of Guinea region that spans southern Nigeria and western Cameroon at the center of the distribution of this species. Remarkably, few studies have included individuals from this region, hindering the examination of chimpanzee population structure across Africa. Here, we analyzed microsatellite genotypes of 94 chimpanzees, including 32 designated as P. t. ellioti. We find that chimpanzees fall into three major populations: (i) Upper Guinea in western Africa (P. t. verus); (ii) the Gulf of Guinea region (P. t. ellioti); and (iii) equatorial Africa (P. t. troglodytes and P. t. schweinfurthii). Importantly, the Gulf of Guinea population is significantly different genetically from the others, sharing a last common ancestor with the populations in Upper Guinea similar to 0.46 million years ago (mya) and equatorial Africa similar to 0.32 mya. Equatorial chimpanzees are subdivided into up to three populations occupying southern Cameroon, central Africa, and eastern Africa, which may have constituted a single population until similar to 0.10-0.11 mya. Finally, occasional hybridization may be occurring between the Gulf of Guinea and southern Cameroon population

Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands. We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3-4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection. We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations

Functional variability at the arylamine N-acetyltransferase genes is associated with drug response in humans and may have been adaptive in the past owing to selection pressure from diet and exposure to toxins during human evolution. Aims: We have characterized nucleotide variation at the NAT1 and NAT2 genes, and at the NATP1 pseudogene in global human populations, including many previously under-represented African populations, in order to identify potential functional variants and to understand the role that natural selection has played in shaping variation at these loci in globally diverse populations. Materials & methods: We have resequenced approximately 2800 bp for each of the NAT1 and NAT2 gene regions, as well as the pseudogene NATP1, in 197 African and 132 nonAfrican individuals. Results & conclusion: We observe a signature of balancing selection maintaining variation in the 3'-UTR of NAT1, suggesting that these variants may play a functional role that is currently undefined. In addition, we observed high levels of nonsynonymous functional variation at the NAT2 locus that differs amongst ethnically diverse populations

Whole-mtDNA genome sequence analysis of ancient African lineages

Studies of human mitochondrial (mt) DNA genomes demonstrate that the root of the human phylogenetic tree occurs in Africa. Although 2 mtDNA lineages with an African origin (haplogroups M and N) were the progenitors of all non-African haplogroups, macrohaplogroup L (including haplogroups L0–L6) is limited to sub-Saharan Africa. Several L haplogroup lineages occur most frequently in eastern Africa (e.g., L0a, L0f, L5, and L3g), but some are specific to certain ethnic groups, such as haplogroup lineages L0d and L0k that previously have been found nearly exclusively among southern African “click” speakers. Few studies have included multiple mtDNA genome samples belonging to haplogroups that occur in eastern and southern Africa but are rare or absent elsewhere. This lack of sampling in eastern Africa makes it difficult to infer relationships among mtDNA haplogroups or to examine events that occurred early in human history. We sequenced 62 complete mtDNA genomes of ethnically diverse Tanzanians, southern African Khoisan speakers, and Bakola Pygmies and compared them with a global pool of 226 mtDNA genomes. From these, we infer phylogenetic relationships amongst mtDNA haplogroups and estimate the time to most recent common ancestor (TMRCA) for haplogroup lineages. These data suggest that Tanzanians have high genetic diversity and possess ancient mtDNA haplogroups, some of which are either rare (L0d and L5) or absent (L0f) in other regions of Africa. We propose that a large and diverse human population has persisted in eastern Africa and that eastern Africa may have been an ancient source of dispersion of modern humans both within and outside of Africa

Antagonistic effects of a Mhc class I allele on malaria-infected house sparrows.

8 pagesInternational audienceGenes of the Major Histocompatibility Complex (Mhc) play a fundamental role during the immune response because MHC molecules expressed on cell surface allow the recognition and presentation of antigenic peptides to T-lymphocytes. Although Mhc alleles have been found to correlate with pathogen resistance in several host-parasite systems, several studies have also reported associations between Mhc alleles and an accrued infection risk or an accelerated disease progression. The existence of these susceptibility alleles is puzzling, as the cost generated by the infection should rapidly eliminate them from the population. Here, we show that susceptibility alleles may be maintained in a population of house sparrows (Passer domesticus) if they have antagonistic effects on different malaria parasites. We found that one Mhc class I allele was associated with a 2.5-fold increase in the risk to be infected with a Plasmodium strain, but with a 6.4-fold reduction in the risk to harbour a Haemoproteus strain. We suggest that this antagonistic effect might arise because Mhc genes can alter the competitive interactions between malaria parasites within the host

African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations [plus Correction]

Background : Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 individuals from 44 indigenous African populations. Results : Genetic structure analyses indicate that among Africans, genetic ancestry is largely partitioned by geography and language, though we observe mixed ancestry in many individuals, consistent with both short- and long-range migration events followed by admixture. Phylogenetic analysis indicates that the San genetic lineage is basal to all modern human lineages. The San and Niger-Congo, Afroasiatic, and Nilo-Saharan lineages were substantially diverged by 160 kya (thousand years ago). In contrast, the San and Central African rainforest hunter-gatherer (CRHG), Hadza hunter-gatherer, and Sandawe hunter-gatherer lineages were diverged by ~ 120–100 kya. Niger-Congo, Nilo-Saharan, and Afroasiatic lineages diverged more recently by ~ 54–16 kya. Eastern and western CRHG lineages diverged by ~ 50–31 kya, and the western CRHG lineages diverged by ~ 18–12 kya. The San and CRHG populations maintained the largest effective population size compared to other populations prior to 60 kya. Further, we observed signatures of positive selection at genes involved in muscle development, bone synthesis, reproduction, immune function, energy metabolism, and cell signaling, which may contribute to local adaptation of African populations. Conclusions : We observe high levels of genomic variation between ethnically diverse Africans which is largely correlated with geography and language. Our study indicates ancient population substructure and local adaptation of Africans

Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers

To reconstruct modern human evolutionary history and identify loci that have shaped hunter-gatherer adaptation, we sequenced the whole genomes of five individuals in each of three different hunter-gatherer populations at >60x coverage: Pygmies from Cameroon and Khoesan-speaking Hadza and Sandawe from Tanzania. We identify 13.4 million variants, substantially increasing the set of known human variation. We found evidence of archaic intro-gression in all three populations, and the distribution of time to most recent common ancestors from these regions is similar to that observed for introgressed regions in Europeans. Additionally, we identify numerous loci that harbor signatures of local adaptation, including genes involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing. Within the Pygmy population, we identify multiple highly differentiated loci that play a role in growth and anterior pituitary function and are associated with height