High mutation rates explain low population genetic divergence at copy-number-variable loci in Homo sapiens

Xin-Sheng Hu; Francis C Yeh; Yang Hu; Li-Ting Deng; Richard A Ennos; Xiaoyang Chen

doi:10.1038/srep43178

High mutation rates explain low population genetic divergence at copy-number-variable loci in Homo sapiens

Sci Rep. 2017 Feb 22:7:43178. doi: 10.1038/srep43178.

Authors

Xin-Sheng Hu^{1

2}, Francis C Yeh³, Yang Hu⁴, Li-Ting Deng^{1

2}, Richard A Ennos⁵, Xiaoyang Chen^{1

2}

Affiliations

¹ Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, South China Agricultural University, Guangdong 510642, China.
² College of Forestry and Landscape Architecture, South China Agricultural University, Guangdong 510642, China.
³ Department of Renewable Resources, 751 General Service Building, University of Alberta, Edmonton, AB T6G 2H1, Canada.
⁴ Department of Computing Science, University of Alberta, Edmonton, AB T6G 2S4, Canada.
⁵ Institute of Evolutionary Biology, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH 9 3JT, United Kingdom.

Abstract

Copy-number-variable (CNV) loci differ from single nucleotide polymorphic (SNP) sites in size, mutation rate, and mechanisms of maintenance in natural populations. It is therefore hypothesized that population genetic divergence at CNV loci will differ from that found at SNP sites. Here, we test this hypothesis by analysing 856 CNV loci from the genomes of 1184 healthy individuals from 11 HapMap populations with a wide range of ancestry. The results show that population genetic divergence at the CNV loci is generally more than three times lower than at genome-wide SNP sites. Populations generally exhibit very small genetic divergence (G_st = 0.05 ± 0.049). The smallest divergence is among African populations (G_st = 0.0081 ± 0.0025), with increased divergence among non-African populations (G_st = 0.0217 ± 0.0109) and then among African and non-African populations (G_st = 0.0324 ± 0.0064). Genetic diversity is high in African populations (~0.13), low in Asian populations (~0.11), and intermediate in the remaining 11 populations. Few significant linkage disequilibria (LDs) occur between the genome-wide CNV loci. Patterns of gametic and zygotic LDs indicate the absence of epistasis among CNV loci. Mutation rate is about twice as large as the migration rate in the non-African populations, suggesting that the high mutation rates play dominant roles in producing the low population genetic divergence at CNV loci.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Copy Number Variations*
Epistasis, Genetic
Genetic Loci*
Genetics, Population*
Healthy Volunteers
Humans
Linkage Disequilibrium
Mutation Rate*
Population Groups