Rapid Evolution of BRCA1 and BRCA2 in Humans and Other Primates

dc.contributor.utaustinauthorLou, Dianne I.en_US
dc.contributor.utaustinauthorMcBee, Ross M.en_US
dc.contributor.utaustinauthorLe, Uyen Q.en_US
dc.contributor.utaustinauthorDemogines, Ann M.en_US
dc.contributor.utaustinauthorSawyer, Sara L.en_US
dc.creatorLou, Dianne I.en_US
dc.creatorMcBee, Ross M.en_US
dc.creatorLe, Uyen Q.en_US
dc.creatorStone, Anne C.en_US
dc.creatorWilkerson, Gregory K.en_US
dc.creatorDemogines, Ann M.en_US
dc.creatorSawyer, Sara L.en_US
dc.description.abstractThe maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers. Results: To obtain a deeper understanding of the evolutionary trajectory of BRCA1, we analyzed complete BRCA1 gene sequences from 23 primate species. We show that specific amino acid sites have experienced repeated selection for amino acid replacement over primate evolution. This selection has been focused specifically on humans and our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). After examining BRCA1 polymorphisms in 7 bonobo, 44 chimpanzee, and 44 rhesus macaque (Macaca mulatta) individuals, we find considerable variation within each of these species and evidence for recent selection in chimpanzee populations. Finally, we also sequenced and analyzed BRCA2 from 24 primate species and find that this gene has also evolved under positive selection. Conclusions: While mutations leading to truncated forms of BRCA1 are clearly linked to cancer phenotypes in humans, there is also an underlying selective pressure in favor of amino acid-altering substitutions in this gene. A hypothesis where viruses are the drivers of this natural selection is discussed.en_US
dc.description.departmentMolecular Biosciencesen_US
dc.description.sponsorshipNational Institutes of Health R01-GM-093086, 8U42OD011197-13en_US
dc.description.sponsorshipNational Science Foundation BCS-07115972en_US
dc.description.sponsorshipBurroughs Wellcome Funden_US
dc.identifier.citationLou, Dianne I., Ross M. McBee, Uyen Q. Le, Anne C. Stone, Gregory K. Wilkerson, Ann M. Demogines, and Sara L. Sawyer. "Rapid evolution of BRCA1 and BRCA2 in humans and other primates." BMC evolutionary biology, Vol. 14, No. 1 (Jul., 2014): 1.en_US
dc.relation.ispartofserialBMC Evolutionary Biologyen_US
dc.rightsAdministrative deposit of works to Texas ScholarWorks: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access or the publisher allows a PDF version of the article to be freely posted online. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en_US
dc.subjectdna damage responseen_US
dc.subjectsimian primatesen_US
dc.subjectcell cycleen_US
dc.subjectpositive selectionen_US
dc.subjectbreast-cancer susceptibilityen_US
dc.subjectamino-acid sitesen_US
dc.subjectancient adaptive evolutionen_US
dc.subjectcodon-substitution modelsen_US
dc.subjectrestriction factor samhd1en_US
dc.subjectdna-damage responseen_US
dc.subjectpositive selectionen_US
dc.subjecthomologous recombinationen_US
dc.subjectevolutionary biologyen_US
dc.subjectgenetics & heredityen_US
dc.titleRapid Evolution of BRCA1 and BRCA2 in Humans and Other Primatesen_US

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