Rapid evolution of BRCA1 and BRCA2in humans and other primates

BMC Evolutionary Biology

Research Article

Dianne I Lou¹  Ross M McBee¹  Ann M Demogines¹  Uyen Q Le¹  Sara L Sawyer¹  Gregory K Wilkerson²  Anne C Stone³ 

[1] Department of Molecular Biosciences, The University of Texas at Austin, 78712, TX, Austin, USA;Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, 78602, TX, Bastrop, USA;School of Human Evolution and Social Change, Arizona State University, 85281, AZ, Tempe, USA;

关键词: DNA damage response;    Simian primates;    Cell cycle;    Positive selection;   

DOI  :  10.1186/1471-2148-14-155

 received in 2014-04-08, accepted in 2014-06-27,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsTo 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.ConclusionsWhile 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.

【 授权许可】

Unknown   
© Lou et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.