Tandem repeat variation in human and great ape populations and its impact on gene expression divergence
Tandem repeat variation in human and great ape populations and its impact on gene expression divergence
ABSTRACT Tandem repeats (TR) are stretches of DNA that are highly variable in length and mutate rapidly, and thus an important source of genetic variation. This variation is highly informative for population and conservation genetics, and has also been associated with several pathological conditions and with gene expression regulation. However, genome-wide surveys of TR variation have been scarce due to the 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, and their impact on gene expression evolution. We found that populations and species diversity patterns can be efficiently captured with short TRs (repeat unit length 1-5 base pairs) with potential applications in conservation genetics. We also 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 base pairs). About one third of the 13,035 one-to-one orthologous genes contained TRs within 5 kilobase pairs of their transcription start site, and had higher expression divergence than genes without such TRs. The same observation held for genes with repeats in their 3’ untranslated region, in introns, and in exons. Using our polymorphism data for the shortest TRs, we found that genes with polymorphic repeats in their promoters showed higher expression divergence in humans and chimpanzees compared to genes with fixed or no TRs in the promoters. Our findings highlight the potential contribution of TRs to recent human evolution through gene regulation.
Sharp Andrew、Greminger Maja P.、Kr¨1tzen Michael、Mittelman David、Robinson Mark D.、Comas David、Carvalho Tiago、Wagner Andreas、Highnam Gareth、Sonay Tugce Bilgin、Bonet Tom¨¤s-Marques
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai SchoolEvolutionary Genetics Group, Anthropological Institute and Museum, University of ZurichEvolutionary Genetics Group, Anthropological Institute and Museum, University of ZurichDepartment of Biological Science and Virginia Bioinformatics Institute, Virginia TechThe Swiss Institute of Bioinformatics||Institute of Molecular Life Sciences, University of ZurichInstitute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu FabraInstitute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu FabraInstitute of Evolutionary Biology and Environmental Studies, University of Zurich||The Swiss Institute of Bioinformatics||The Santa Fe InstituteDepartment of Biological Science and Virginia Bioinformatics Institute, Virginia TechInstitute of Evolutionary Biology and Environmental Studies, University of Zurich||The Swiss Institute of BioinformaticsInstitute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra||Centro Nacional de An¨￠lisis Gen¨?mico (CNAG)
遗传学分子生物学生物科学现状、生物科学发展
tandem repeatspopulation diversitygene expression
Sharp Andrew,Greminger Maja P.,Kr¨1tzen Michael,Mittelman David,Robinson Mark D.,Comas David,Carvalho Tiago,Wagner Andreas,Highnam Gareth,Sonay Tugce Bilgin,Bonet Tom¨¤s-Marques.Tandem repeat variation in human and great ape populations and its impact on gene expression divergence[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/015784.点此复制
评论