Full metadata
Title
Rapid evolution of BRCA1 and BRCA2in humans and other primates
Description
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.
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.
Date Created
2014-07-11
Contributors
- Lou, Dianne I. (Author)
- McBee, Ross M. (Author)
- Le, Uyen Q. (Author)
- Stone, Anne (Author)
- Wilkerson, Gregory K. (Author)
- Demogines, Ann M. (Author)
- Sawyer, Sara L. (Author)
- College of Liberal Arts and Sciences (Contributor)
- School of Human Evolution and Social Change (Contributor)
- School of Life Sciences (Contributor)
Resource Type
Extent
13 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Identifier
Digital object identifier: 10.1186/1471-2148-14-155
Identifier Type
International standard serial number
Identifier Value
1471-2148
Series
BMC EVOLUTIONARY BIOLOGY
Handle
https://hdl.handle.net/2286/R.I.41835
Preferred Citation
Lou, D. I., Mcbee, R. M., Le, U. Q., Stone, A. C., Wilkerson, G. K., Demogines, A. M., & Sawyer, S. L. (2014). Rapid evolution of BRCA1 and BRCA2 in humans and other primates. BMC Evolutionary Biology, 14(1), 155. doi:10.1186/1471-2148-14-155
Level of coding
minimal
Cataloging Standards
Note
The electronic version of this article is the complete one and can be found online at: https://bmcevolbiol.biomedcentral.com/articles/10.1186/1471-2148-14-155
System Created
- 2017-03-20 03:57:47
System Modified
- 2021-08-16 02:23:30
- 3 years 3 months ago
Additional Formats