Variação sequencial repetida em populações humanas e de grandes primatas, e o seu impacto sobre a expressão gênica de divergência

segunda-feira, novembro 16, 2015

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

Tugce Bilgin Sonay 1,2,11, Tiago Carvalho 3,11, Mark D. Robinson 2,4, Maja P. Greminger 5, Michael Krützen 5, David Comas 3, Gareth Highnam 6, David Mittelman 6, Andrew Sharp 7, Tomàs Marques-Bonet 3,8,9,11 and Andreas Wagner 1,2,10,11

1Institute of Evolutionary Biology and Environmental Studies, University of Zurich, CH-805 Zurich, Switzerland;

2The Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;

3Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain;

4Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland;

5Evolutionary Genetics Group, Anthropological Institute and Museum, University of Zurich, CH-8057 Zurich, Switzerland;

6Department of Biological Science and Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia 24061, USA;

7Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai School, New York, New York 10029, USA;

8Centro Nacional de Análisis Genómico (CNAG), PCB, Barcelona, 08028 Catalonia, Spain;

9Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain;

10The Santa Fe Institute, Santa Fe, New Mexico 87501, USA

Corresponding authors: andreas.wagner{at}, tomas.marques{at}

↵11 These authors contributed equally to this work.


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.


[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at

Received February 16, 2015.

Accepted August 14, 2015.

© 2015 Bilgin Sonay et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at


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