Rapid evolution of BRCA1 and BRCA2 in humans and other primates

BMC Evolutionary Biology

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

[1] Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA;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;School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85281, USA

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

Others  :  856311
DOI  :  10.1186/1471-2148-14-155

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

【 摘 要 】

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.

【 授权许可】

   
2014 Lou et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Mullen P, Miller WR, Mackay J, Fitzpatrick DR, Langdon SP, Warner JP: BRCA1 5382insC mutation in sporadic and familial breast and ovarian carcinoma in Scotland. Br J Cancer 1997, 75:1377-1380.
• [2]O’Donovan PJ, Livingston DM: BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis 2010, 31:961-967.
• [3]Hemel D, Domchek SM: Breast Cancer Predisposition Syndromes. Hematol Oncol Clin North Am 2010, 24:799-814.
• [4]Ludwig T, Chapman DL, Papaioannou VE, Efstratiadis A: Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev 1997, 11:1226-1241.
• [5]Hurst LD, Pál C: Evidence for purifying selection acting on silent sites in BRCA1. Trends Genet 2001, 17:62-65.
• [6]Huttley GA, Easteal S, Southey MC, Tesoriero A, Giles GG, McCredie MR, Hopper JL, Venter DJ: Adaptive evolution of the tumour suppressor BRCA1 in humans and chimpanzees. Australian Breast Cancer Family Study. Nat Genet 2000, 25:410-413.
• [7]Yang Z, Nielsen R: Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol 2002, 19:908-917.
• [8]Fleming MA, Potter JD, Ramirez CJ, Ostrander GK, Ostrander EA: Understanding missense mutations in the BRCA1 gene: an evolutionary approach. Proc Natl Acad Sci U S A 2003, 100:1151-1156.
• [9]Burk-Herrick A, Scally M, Amrine-Madsen H, Stanhope MJ, Springer MS: Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans. Mamm Genome 2006, 17:257-270.
• [10]O’Connell MJ: Selection and the Cell Cycle: Positive Darwinian Selection in a Well-Known DNA Damage Response Pathway. J Mol Evol 2010, 71:444-457.
• [11]Pavlicek A, Noskov V, Kouprina N, Barrett JC, Jurka J, Larionov V: Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. Hum Mol Genet 2004, 13:2737-2751.
• [12]Meyerson NR, Sawyer SL: Two-stepping through time: mammals and viruses. Trends Microbiol 2011, 19:286-294.
• [13]Yang Z: PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 2007, 24:1586-1591.
• [14]Durocher F, Shattuck-Eidens D, McClure M, Labrie F, Skolnick MH, Goldgar DE, Simard J: Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. Hum Mol Genet 1996, 5:835-842.
• [15]Dunning AM, Chiano M, Smith NR, Dearden J, Gore M, Oakes S, Wilson C, Stratton M, Peto J, Easton D, Clayton D, Ponder BA: Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum Mol Genet 1997, 6:285-289.
• [16]Mizuta R, LaSalle JM, Cheng HL, Shinohara A, Ogawa H, Copeland N, Jenkins NA, Lalande M, Alt FW: RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein. Proc Natl Acad Sci U S A 1997, 94:6927-6932.
• [17]Wong AKC, Pero R, Ormonde PA, Tavtigian SV, Bartel PL: RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J Biol Chem 1997, 272:31941-31944.
• [18]Holloman WK: Unraveling the mechanism of BRCA2 in homologous recombination. Nat Struct Mol Biol 2011, 18:748-754.
• [19]Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR: Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 2002, 420:287-293.
• [20]Rajendra E, Venkitaraman AR: Two modules in the BRC repeats of BRCA2 mediate structural and functional interactions with the RAD51 recombinase. Nucleic Acids Res 2009, 38:82-96.
• [21]Clark AG, Glanowski S, Nielsen R, Thomas PD, Kejariwal A, Todd MA, Tanenbaum DM, Civello D, Lu F, Murphy B, Ferriera S, Wang G, Zheng X, White TJ, Sninsky JJ, Adams MD, Cargill M: Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. Science 2003, 302:1960-1963.
• [22]Vallender EJ, Lahn BT: Positive selection on the human genome. Hum Mol Genet 2004, 13:R245-R254. Spec No 2
• [23]Sawyer SL, Emerman M, Malik HS: Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS Biol 2004, 2:E275.
• [24]Sawyer SL, Wu LI, Emerman M, Malik HS: Positive selection of primate TRIM5alpha identifies a critical species-specific retroviral restriction domain. Proc Natl Acad Sci U S A 2005, 102:2832-2837.
• [25]Elde NC, Child SJ, Geballe AP, Malik HS: Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature 2009, 457:485-489.
• [26]Lim ES, Malik HS, Emerman M: Ancient Adaptive Evolution of Tetherin Shaped the Functions of Vpu and Nef in Human Immunodeficiency Virus and Primate Lentiviruses. J Virol 2010, 84:7124-7134.
• [27]Laguette N, Rahm N, Sobhian B, Chable-Bessia C, Münch J, Snoeck J, Sauter D, Switzer WM, Heneine W, Kirchhoff F, Delsuc F, Telenti A, Benkirane M: Evolutionary and Functional Analyses of the Interaction between the Myeloid Restriction Factor SAMHD1 and the Lentiviral Vpx Protein. Cell Host and Microbe 2012, 11:205-217.
• [28]Lim ES, Fregoso OI, McCoy CO, Matsen FA, Malik HS, Emerman M: The Ability of Primate Lentiviruses to Degrade the Monocyte Restriction Factor SAMHD1 Preceded the Birth of the Viral Accessory Protein Vpx. Cell Host and Microbe 2012, 11:194-204.
• [29]Demogines A, East AM, Lee J-H, Grossman SR, Sabeti PC, Paull TT, Sawyer SL: Ancient and Recent Adaptive Evolution of Primate Non-Homologous End Joining Genes. PLoS Genet 2010, 6:e1001169.
• [30]Sawyer SL, Malik HS: Positive selection of yeast nonhomologous end-joining genes and a retrotransposon conflict hypothesis. Proc Natl Acad Sci U S A 2006, 103:17614-17619.
• [31]Lilley CE, Schwartz RA, Weitzman MD: Using or abusing: viruses and the cellular DNA damage response. Trends Microbiol 2007, 15:119-126.
• [32]Chaurushiya MS, Weitzman MD: Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair (Amst) 2009, 8:1166-1176.
• [33]Stracker TH, Carson CT, Weitzman MD: Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature 2002, 418:348-352.
• [34]Lilley CE, Carson CT, Muotri AR, Gage FH, Weitzman MD: DNA repair proteins affect the lifecycle of herpes simplex virus 1. Proc Natl Acad Sci U S A 2005, 102:5844-5849.
• [35]Mohni KN, Mastrocola AS, Bai P, Weller SK, Heinen CD: DNA mismatch repair proteins are required for efficient herpes simplex virus 1 replication. J Virol 2011, 85:12241-12253.
• [36]Lees-Miller SP, Long MC, Kilvert MA, Lam V, Rice SA, Spencer CA: Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0. J Virol 1996, 70:7471-7477.
• [37]Lilley CE, Chaurushiya MS, Boutell C, Everett RD, Weitzman MD: The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. PLoS Pathog 2011, 7:e1002084.
• [38]Zimmerman ES, Chen J, Andersen JL, Ardon O, Dehart JL, Blackett J, Choudhary SK, Camerini D, Nghiem P, Planelles V: Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear BRCA1 and gamma-H2AX focus formation. Mol Cell Biol 2004, 24:9286-9294.
• [39]Nakai-Murakami C, Shimura M, Kinomoto M, Takizawa Y, Tokunaga K, Taguchi T, Hoshino S, Miyagawa K, Sata T, Kurumizaka H, Yuo A, Ishizaka Y: HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination. Oncogene 2006, 26:477-486.
• [40]Daniel R, Katz RA, Skalka AM: A Role for DNA-PK in Retroviral DNA Integration. Science 1999, 284:644-647.
• [41]Daniel R, Greger JG, Katz RA, Taganov KD, Wu X, Kappes JC, Skalka AM: Evidence that stable retroviral transduction and cell survival following DNA integration depend on components of the nonhomologous end joining repair pathway. J Virol 2004, 78:8573-8581.
• [42]Smith JA, Wang F-X, Zhang H, Wu K-J, Williams KJ, Daniel R: Evidence that the Nijmegen breakage syndrome protein, an early sensor of double-strand DNA breaks (DSB), is involved in HIV-1 post-integration repair by recruiting the ataxia telangiectasia-mutated kinase in a process similar to, but distinct from, cellular DSB repair. Virol J 2008, 5:11.
• [43]Zhong Q, Chen C-F, Chen P-L, Lee W-H: BRCA1 Facilitates Microhomology-mediated End Joining of DNA Double Strand Breaks. J Biol Chem 2002, 277:28641-28647.
• [44]Lau A, Kanaar R, Jackson SP, O’Connor MJ: Suppression of retroviral infection by the RAD52 DNA repair protein. EMBO J 2004, 23:3421-3429.
• [45]Lloyd AG, Tateishi S, Bieniasz PD, Muesing MA, Yamaizumi M, Mulder LCF: Effect of DNA Repair Protein Rad18 on Viral Infection. PLoS Pathog 2006, 2:e40.
• [46]Cosnefroy O, Tocco A, Lesbats P, Thierry S, Calmels C, Wiktorowicz T, Reigadas S, Kwon Y, De Cian A, Desfarges S, Bonot P, San Filippo J, Litvak S, Le Cam E, Rethwilm A, Fleury H, Connell PP, Sung P, Delelis O, Andreola ML, Parissi V: Stimulation of the Human RAD51 Nucleofilament Restricts HIV-1 Integration In Vitro and in Infected Cells. J Virol 2011, 86:513-526.
• [47]Carter AJ, Nguyen AQ: Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles. BMC Med Genet 2011, 12:160.
• [48]Crespi BJ, Summers K: Positive selection in the evolution of cancer. Biol Rev 2006, 81:407.
• [49]Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG: Clustal W and Clustal X version 2.0. Bioinformatics 2007, 23:2947-2948.
• [50]Yang Z: PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 1997, 13:555-556.
• [51]Yang Z: Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 1998, 15:568-573.
• [52]Goldman N, Yang Z: A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 1994, 11:725-736.
• [53]Yang Z, Nielsen R, Goldman N, Pedersen AM: Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 2000, 155:431-449.
• [54]Nielsen R, Yang Z: Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 1998, 148:929-936.
• [55]Wong WSW, Yang Z, Goldman N, Nielsen R: Accuracy and power of statistical methods for detecting adaptive evolution in protein coding sequences and for identifying positively selected sites. Genetics 2004, 168:1041-1051.
• [56]Yang Z, Wong WSW, Nielsen R: Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 2005, 22:1107-1118.
• [57]Rodriguez S, Gaunt TR, Day INM: Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol 2009, 169:505-514.