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Bioinformatics Advance Access published online on April 26, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm137
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Human Recombination Rates Are Increased Around Accelerated Conserved Regions - Evidence for Continued Selection ?

Jan Freudenberg 1, Ying-Hui Fu 1 and Louis J. Ptácek 1,2

1University of California San Francisco, Department of Neurology, Institute of Human Genetics, 1550 4th Street, San Francisco, CA 94158-2922, USA
2Howard Hughes Medical Institute, University of California San Francisco

To whom correspondence should be addressed. Jan Freudenberg, E-mail: jan.freudenberg{at}ucsf.edu


  Abstract

Motivation: We hypothesized that recombination rates might be increased at genetic loci that are subject to more intense selection. Here we test this hypothesis by using a recently published set of accelerated conserved regions and fine scale recombination rate estimates provided by the HapMap project.

Results: We observed that fine scale recombination rates are increased around conserved noncoding regions that show accelerated evolution in human or chimp, as compared to noncoding regions showing accelerated evolution in mouse and those being conserved between human and fugu. Recombination rates around hominid accelerated conserved regions (ACRs) are furthermore increased as compared to exonic regions. On the other hand, GC-content is reduced around ACRs, excluding a major confounding influence of GC-content on the observed variation in recombination rate.

Conclusion: Our observations indicate that selection intensity could be an important determinant of local recombination rate variation and that continued positive selection might act at many ACR loci. Alternatively, a confounding factor needs to be found that causes a congruent signal in recombination rate estimates based on human polymorphism data and in the comparative genomic data. Researchers who consider the explanation involving selection as more likely may expect more common functional sequence variants at ACRs in genetic association studies.

Associate Editor: Prof. Keith Crandall

Received on November 30, 2006; revised on March 30, 2007; accepted on April 2, 2007

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