Tandem repeat variation in human and great ape populations and its impact on gene expression divergence

Tandem repeats (TRs) are stretches of DNA that are highly variable in length and mutate rapidly. They are thus an important source of genetic variation. This variation is highly informative for population and conservation genetics. It has also been associated with several pathological conditions and with gene expression regulation. However, genome-wide surveys of TR variation in humans and closely related species have been scarce due to technical difficulties derived from short-read technology. Here we explored the genome-wide diversity of TRs in a panel of 83 human and nonhuman great ape genomes, in a total of six different species, and studied their impact on gene expression evolution. We found that population diversity patterns can be efficiently captured with short TRs (repeat unit length, 1–5 bp). We examined the potential evolutionary role of TRs in gene expression differences between humans and primates by using 30,275 larger TRs (repeat unit length, 2–50 bp). Genes that contained TRs in the promoters, in their 3′ untranslated region, in introns, and in exons had higher expression divergence than genes without repeats in the regions. Polymorphic small repeats (1–5 bp) had also higher expression divergence compared with genes with fixed or no TRs in the gene promoters. Our findings highlight the potential contribution of TRs to human evolution through gene regulation.A.W. and T.B.S. acknowledge support through Swiss National Science Foundation grant 31003A_146137, as well as through the University Priority Research Program in Evolutionary Biology at the University of Zurich. T.M.B. was supported by a European Research Council (ERC) starting grant (260372), ICREA, EMBO Young Investigator Award, and the Ministerio de Ciencia e Innovación (MICINN) (BFU2014-55090-P, Spain). This work was also supported by the National Institutes of Health (NIH) grants HG006696, MH097018, and DA033660, and by the March of Dimes Foundation grant 6-FY13-92.Peer reviewe