Genome-wide detection of natural selection in African Americans pre- and post-admixture

Abstract

It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre-and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific highrisk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre-and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.

Copy number variations and genetic admixtures in three Xinjiang ethnic minority groups

“…To identify these outliers, we applied a strategy analogous to one that was recently used to assess natural selection among African Americans. 21 We calculated the ancestry-biased F ST between the expected and observed allele frequency for each admixed population (Supplementary Figure 4). CNVRs in the top 0.5 percentile were regarded as ancestry-biased CNVs (Table 2).…”

Distribution of ancestral chromosomal segments in admixed genomes and its implications for inferring population history and admixture mapping

“…Detailed information about the African-American and Mexican data sets has been described in previous studies. 1,25 Briefly, the African-American data set contained 2214 AfricanAmericans and 268 samples from their three putative parental populations. The 268 samples representing the three putative parental populations consisted of 112 European samples (Utah residents with northern and western European ancestry from the CEPH collection; CEU), 112 African samples (Yoruba in Ibadan, Nigeria; YRI) and 44 Amerindian samples.…”

Population Genetics in the Genomic Era

“…HAPMIX permits small rates of miscopying from the ancestral haplotype, modeling unphased diploid data from the admixed population with the HMM. Our simulations showed that HAMPIX performed better compared with other methods when very recent admixed population were investigated [82].…”

“…Thus, some genomic regions in admixed population might show excess of a particular ancestry, possibly attributable to selection pressures after the population admixture [84]. By far, several studies have used the genome-wide data to scan for signatures of selection in admixed populations [82].…”

“…However, these approaches cannot be directly applied on recently admixed population due to the confused population structure. Jin et al [82] developed a new strategy to detect natural selection in admixed population such as African American, in which they reconstructed an ancestral African population (AAF) from African components of ancestry in African American and compared the population differentiation between indigenous African and AAF. Many targets of selection identified by this approach were associated with African-Americans specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to new environments [82].…”