近日,，Molecular Biology and Evolution雜志上在線發(fā)表了中國科學院昆明動物研究所張亞平院士等人的研究成果,，RNASEL基因進化與功能的相關性研究取得了重大突破。
核糖核酸酶L（RNASEL）是免疫2-5A系統(tǒng)中的核酸酶,，在免疫抗病毒過程中起到重要作用,。另外，RNASEL也是非常重要的前列腺癌基因,，在人群中RNASEL基因的多個多態(tài)性位點與前列腺癌有顯著相關性,。
為研究RNASEL在抗病毒以及癌癥相關性之間的關聯(lián)，中國科學院昆明動物研究所張亞平院士,，吳東東博士,，云南大學靳偉博士等研究了靈長類RNASEL基因的進化特征發(fā)現(xiàn)，該基因受到達爾文正選擇的作用,，且主要作用于C端的核酸酶結構域（該區(qū)域負責消化外源病原物的RNA）,，以及N端的ankyrin重復結構域（負責接收外界信號）。
進一步研究該基因在現(xiàn)代人群中的群體遺傳學特征發(fā)現(xiàn),，攜帶541D等位基因的單倍型受到達爾文正選擇的作用,。外源病原物的感染是導致前列腺癌的重要原因，而攜帶541D的個體抵抗病毒能力較強,，因而與541D的頻率和前列腺癌的發(fā)生率呈負相關是一致的,。
傳統(tǒng)的觀點認為，癌癥相關基因受到達爾文正選擇作用的主要原因是基因多效性：基因的變異體在一項功能上有利（例如抵抗外源病原物）受到正選擇作用,，由于基因功能的多效性,，在另一功能上不利，因而增加癌癥發(fā)病的風險,。該研究發(fā)現(xiàn)正選擇作用的變異體也能夠降低癌癥發(fā)病的風險（如圖）：宿主的一些免疫基因的變異體能夠抵抗外源物,，而外源病原物是致癌的重要原因，因而該基因受到正選擇作用而發(fā)生快速進化,，也就能降低癌癥的風險,。（生物谷Bioon.com）
doi:10.1093/molbev/mss123
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Positive selection on the gene RNASEL: correlation between patterns of evolution and function
Wei Jin, Dong-Dong Wu, Xin Zhang, David M Irwin and Ya-Ping Zhang
RNASEL is a 2-5A-dependent endoribonuclease that is a component of the interferon-induced 2-5A system, which plays a crucial role in the antiviral and apoptotic activities of interferons. In humans, many polymorphic sites within the RNASEL gene have been associated with an increased risk of developing prostate cancer. Here, we obtained coding sequences for the RNASEL gene from 11 primates, and found evidence that positive selection has operated on the C-terminal endoribonuclease domain and the N-terminal ankyrin repeats domain of the protein, domains that directly interact with virus (i.e., ankyrin repeats are responsible for receiving environmental signals and the endoribonuclease catalyses the destruction of the pathogenic viral RNA). To extend this finding we studied variation within this gene in modern human populations by resequencing alleles from 144 individuals representing four separate populations. Interestingly, the frequency of the 541D allele shows a negative association with the incidence rate of prostate cancer in World-wide populations, and haplotypes containing the 541D polymorphisms demonstrate signatures of positive selection. RNASEL variants having the 541D haplotype likely have a greater ability to defend against infections by viruses, thus the loss of this activity may be associated with the development of prostate cancer. We provide evidence that positive selection has operated on the RNASEL gene, and its evolution is correlated with its function in pathogen defense and cancer
