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.
Institute of Evolutionary Biology and Environmental Studies, University of Zurich, CH-805 Zurich, Switzerland; The Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
Tugce
T
Bilgin Sonay
Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
Tiago
T
Carvalho
The Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland;
Mark D
MD
Robinson
Evolutionary Genetics Group, Anthropological Institute and Museum, University of Zurich, CH-8057 Zurich, Switzerland;
Maja P
MP
Greminger
Evolutionary Genetics Group, Anthropological Institute and Museum, University of Zurich, CH-8057 Zurich, Switzerland;
Michael
M
Krützen
Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
David
D
Comas
Department of Biological Science and Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia 24061, USA;
Gareth
G
Highnam
Department of Biological Science and Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia 24061, USA;
David
D
Mittelman
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai School, New York, New York 10029, USA;
Andrew
A
Sharp
Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Centro Nacional de Análisis Genómico (CNAG), PCB, Barcelona, 08028 Catalonia, Spain; Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain;
Tomàs
T
Marques-Bonet
Institute of Evolutionary Biology and Environmental Studies, University of Zurich, CH-805 Zurich, Switzerland; The Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; The Santa Fe Institute, Santa Fe, New Mexico 87501, USA.
Andreas
A
Wagner
D020413:3' Untranslated Regions; D000818:Animals; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D014644:Genetic Variation; D015894:Genome, Human; D060005:Genotyping Techniques; D006801:Humans; D007438:Introns; D008297:Male; D018895:Microsatellite Repeats; D011323:Primates / Q000235:genetics*; D011401:Promoter Regions, Genetic
D020413:3' Untranslated Regions