Evidence of Recent Intricate Adaptation in Human Populations

PLoS One. 2016 Dec 19;11(12):e0165870. doi: 10.1371/journal.pone.0165870. eCollection 2016.

Abstract

Recent human adaptations have shaped population differentiation in genomic regions containing putative functional variants, mostly located in predicted regulatory elements. However, their actual functionalities and the underlying mechanism of recent adaptation remain poorly understood. In the current study, regions of genes and repeats were investigated for functionality depending on the degree of population differentiation, FST or ΔDAF (a difference in derived allele frequency). The high FST in the 5´ or 3´ untranslated regions (UTRs), in particular, confirmed that population differences arose mainly from differences in regulation. Expression quantitative trait loci (eQTL) analyses using lymphoblastoid cell lines indicated that the majority of the highly population-specific regions represented cis- and/or trans-eQTL. However, groups having the highest ΔDAFs did not necessarily have higher proportions of eQTL variants; in these groups, the patterns were complex, indicating recent intricate adaptations. The results indicated that East Asian (EAS) and European populations (EUR) experienced mutual selection pressures. The mean derived allele frequency of the high ΔDAF groups suggested that EAS and EUR underwent strong adaptation; however, the African population in Africa (AFR) experienced slight, yet broad, adaptation. The DAF distributions of variants in the gene regions showed clear selective pressure in each population, which implies the existence of more recent regulatory adaptations in cells other than lymphoblastoid cell lines. In-depth analysis of population-differentiated regions indicated that the coding gene, RNF135, represented a trans-regulation hotspot via cis-regulation by the population-specific variants in the region of selective sweep. Together, the results provide strong evidence of actual intricate adaptation of human populations via regulatory manipulation.

MeSH terms

  • Adaptation, Biological
  • Asian People / genetics*
  • Black People / genetics*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genetic Variation
  • Genetics, Population
  • Humans
  • Quantitative Trait Loci*
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Ubiquitin-Protein Ligases / genetics*
  • White People / genetics*

Substances

  • RNF135 protein, human
  • Ubiquitin-Protein Ligases

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean Government (MSIP) (2013R1A1A3006685, 2014K2A7A1044502, and 2015R1D1A1A01059302). The supercomputing resources were supported by the Korea Institute of Science and Technology Information (KISTI), with grant no. KSC-2014-C2-019.