Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations

Genetics. 2018 Jul;209(3):907-920. doi: 10.1534/genetics.118.300826. Epub 2018 May 16.


Ampliconic genes are multicopy, with the majority found on sex chromosomes and enriched for testis-expressed genes. While ampliconic genes have been associated with the emergence of hybrid incompatibilities, we know little about their copy number distribution and their turnover in human populations. Here, we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read depth on modified X and Y chromosome targets containing only one repetition of each ampliconic gene. Our results reveal extensive standing variation in copy number both within and between human populations for several ampliconic genes. For the Y chromosome, we can infer multiple independent amplifications and losses of these gene copies even within closely related Y haplogroups, that diversified < 50,000 years ago. Moreover, X- and Y-linked ampliconic genes seem to have a faster amplification dynamic than autosomal multicopy genes. Looking at expression data from another study, we also find that X- and Y-linked ampliconic genes with extensive CNV are significantly more expressed than genes with no CNV during meiotic sex chromosome inactivation (for both X and Y) and postmeiotic sex chromosome repression (for the Y chromosome only). While we cannot rule out that the XY-linked ampliconic genes are evolving neutrally, this study gives insights into the distribution of copy number within human populations and demonstrates an extremely fast turnover in copy number of these regions.

Keywords: ampliconic genes; copy number variation; human population genetics; sex chromosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, X / genetics*
  • Chromosomes, Human, Y / genetics*
  • Computational Biology / methods
  • Evolution, Molecular
  • Female
  • Gene Dosage*
  • Genes, X-Linked*
  • Genes, Y-Linked*
  • Genetics, Population
  • Humans
  • Male
  • Meiosis
  • Multigene Family