Open Access Highly Accessed Research article

Rapid evolution of BRCA1 and BRCA2 in humans and other primates

Dianne I Lou1, Ross M McBee1, Uyen Q Le1, Anne C Stone2, Gregory K Wilkerson3, Ann M Demogines1 and Sara L Sawyer1*

Author Affiliations

1 Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA

2 School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85281, USA

3 Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Bastrop, TX 78602, USA

For all author emails, please log on.

BMC Evolutionary Biology 2014, 14:155  doi:10.1186/1471-2148-14-155

Published: 11 July 2014

Abstract

Background

The 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.

Keywords:
DNA damage response; Simian primates; Cell cycle; Positive selection