Pfeffer Claire M, Ho Benjamin N, Singh Amareshwar T K
Department of Biology, Division of Natural and Social Sciences, Carthage College, Kenosha, WI, U.S.A.
Cancer Genomics Proteomics. 2017 Sep-Oct;14(5):293-298. doi: 10.21873/cgp.20040.
BRCA1 and BRCA2 are both tumor suppressors whose mutations are the cause of most hereditary breast cancers. Both genes are highly involved in ensuring genome stability. BRCA1 homologs are found in the plant and animal kingdoms while BRCA2 homologs are additionally found in the fungi kingdom. The initial origin of both genes remains unknown, however it is expected that the common ancestors originated around 1.6 billion years ago prior to the kingdoms diverging. There has been a great amount of divergence between homologs that is not observed in other tumor suppressors with only functionally important domains conserved. This divergence continues today with evidence of primate BRCA1/2 evolution. Cancer-associated mutations have been found to occur at conserved sites, indicating that conserved sites are important for function. In this study, we present a review on the phylogenesis of BRCA1 and BRCA2.
BRCA1和BRCA2都是肿瘤抑制基因,其突变是大多数遗传性乳腺癌的病因。这两个基因在确保基因组稳定性方面都高度相关。BRCA1的同源物存在于植物和动物界,而BRCA2的同源物还存在于真菌界。这两个基因的最初起源仍然未知,然而预计其共同祖先在16亿年前左右,即各生物界分化之前就已出现。同源物之间存在大量差异,这在其他肿瘤抑制基因中未观察到,只有功能重要的结构域得以保留。这种差异至今仍在持续,有灵长类BRCA1/2进化的证据。已发现癌症相关突变发生在保守位点,这表明保守位点对功能很重要。在本研究中,我们对BRCA1和BRCA2的系统发生进行了综述。