Inter-population Differences in Retrogene Loss and Expression in Humans

PLoS Genet. 2015 Oct 16;11(10):e1005579. doi: 10.1371/journal.pgen.1005579. eCollection 2015 Oct.


Gene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications. In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations. In addition, we examined retrocopy expression levels using RNA-Seq data derived from the Ilumina BodyMap project, as well as data from lymphoblastoid cell lines provided by the Geuvadis Consortium. We also developed a new approach to detect novel retrocopies absent from the reference human genome. We experimentally confirmed the existence of the detected retrocopies and determined their presence or absence in the human genomes of 17 different populations. Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion. Most of these RDVs had not been previously reported. We experimentally confirmed the expression of 11 ancestral retrogenes that underwent deletion in certain individuals. The frequency of their deletion, with the exception of one retrogene, is very low. The expression, conservation and low rate of deletion of the remaining 10 retrocopies may suggest some functionality. Aside from the presence or absence of expressed retrocopies, we also searched for differences in retrocopy expression levels between populations, finding 9 retrogenes that undergo statistically significant differential expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evolution, Molecular*
  • Gene Duplication*
  • Gene Expression Regulation
  • Genome, Human*
  • High-Throughput Nucleotide Sequencing
  • Human Genome Project
  • Humans
  • Polymorphism, Genetic*
  • Primates / genetics

Grant support

This work was supported by the National Science Centre (PL), grant 2011/01/B/ST6/06868 to AP, grant 2013/11/B/NZ2/02598 to IM, grant 2013/09/N/NZ2/01221 to MK; KNOW RNA Research Centre in Poznań, 01/KNOW2/2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.