Rapid evolution of BRCA1 and BRCA2 in humans and other primates.
Rapid evolution of BRCA1 and BRCA2 in humans and other primates.
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DOI：
10.1186/1471-2148-14-155
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发表时间：
2014-07-11
影响因子：
3.4
通讯作者：
Sawyer SL
中科院分区：
文献类型：
--
作者：
Lou DI;McBee RM;Le UQ;Stone AC;Wilkerson GK;Demogines AM;Sawyer SL
维持染色体的完整性是每个生物体的基本任务，细胞修复机制的存在是为了防止对DNA的损伤。考虑到这一过程的重要性，预计DNA修复蛋白将在进化上保守，随着时间的推移表现出非常小的序列变化。然而，据报道，BRCA1是一种参与DNA修复的必需基因，尽管该基因中的许多蛋白质改变突变会显著增加乳腺癌和卵巢癌的风险，但它正在迅速进化。为了更深入地了解BRCA1的进化轨迹，我们分析了23种灵长类动物的完整BRCA1基因序列。我们表明，特定的氨基酸位点经历了重复的选择，在灵长类动物进化的氨基酸替换。这种选择特别集中在人类和我们最近的亲戚，黑猩猩（Pan troglodytes）和倭黑猩猩（Pan paniscus）。在检查7倭黑猩猩，44黑猩猩，44恒河猴（猕猴）个体的BRCA1多态性后，我们发现这些物种中的每一个都有相当大的变化，并为最近在黑猩猩种群中的选择提供了证据。最后，我们还对24种灵长类动物的BRCA2基因进行了测序和分析，发现该基因也在正选择下进化。虽然导致BRCA1截短形式的突变与人类癌症表型明显相关，但该基因中也存在有利于氨基酸改变取代的潜在选择压力。一个假设，病毒是这种自然选择的驱动程序进行了讨论。
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. 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. 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.
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影响因子：
15.9
作者：
Meyerson NR;Sawyer SL
通讯作者：
Sawyer SL
BRCA1 5382INSC突变在苏格兰零星和家族性乳房和卵巢癌中。
影响因子：
8.8
作者：
Mullen, P;Miller, WR;Mackay, J;Fitzpatrick, DR;Langdon, SP;Warner, JP
通讯作者：
Warner, JP
影响因子：
6.7
作者：
Lilley CE;Chaurushiya MS;Boutell C;Everett RD;Weitzman MD
通讯作者：
Weitzman MD
影响因子：
2.5
作者：
Burk-Herrick, A;Scally, M;Springer, MS
通讯作者：
Springer, MS
影响因子：
3.5
作者：
Dunning, AM;Chiano, M;Ponder, BAJ
通讯作者：
Ponder, BAJ