鑫达医学翻译公司-最好的医学翻译、病历翻译、药学翻译、sci论文翻译、生物翻译网站!您最好的医学论文翻译合作伙伴!
设为首页 | 加入收藏 | 联系我们
首页 > 翻译讲堂 >

上位效应是分子进化的主要影响因素

发布者:鑫达医学翻译 发布时间:2012-10-17阅读:

     随着分子生物学技术不断进步以及基因组信息的日益完善,人们对进化的认识也越来越深入,但是对那些主导长期进化的力量和机制依然是未知的。目前的研究表明,基因进化过程中蛋白氨基酸残基替换有大部分是由正向选择所固定,而上位效应(epistasis,在氨基酸序列层面是指某种表型中被选择出来的氨基酸替代在另外一种表型情况下可能是有害的)如何影响蛋白的长期进化一直未被揭示。《自然》杂志10月14日在线报道了Breen等的研究成果,他们把16类细胞内蛋白(其中14类细胞器蛋白和2类核编码蛋白)在短期内的进化速率的数据分析和在不同位点上氨基酸残基的使用频次的数据分析结合起来,定量地评估了上位效应对于蛋白长期进化的影响模式。研究人员首先通过对每类蛋白的至少1000个来自于具有分散系统发生关系(即亲缘关系)物种的直系同源蛋白进行多序列比对,发现平均每个相同的氨基酸位点大约存在8种不同的氨基酸替代。因此,如果在上位效应不发挥作用的情况下,平均每个位点应该为所有可能替代的2/5——即(8*2/5),而且氨基酸替代的进化速率应比中性进化条件下低大约3/5。但是他们的数据表明,实际的氨基酸替代速率却是理论推得的中性进化的速率的1/20,两者相差一个数量级。这说明上位效全面地影响了蛋白的进化过程:90%的氨基酸替代在一种遗传背景下是中性的或者有益的,而在另外的遗传背景下(即不同的物种)是有害的。这一研究成果表明氨基酸替代在不同物种中的适应效应是不一样的,这是第一次把上位效应的机理定量地应用于分析蛋白的长期进化,这无论是对于科学家从一个全新的角度理解基因和蛋白的进化,还是对于通过实验进化设计蛋白药物和筛选具有特定效用的蛋白都是大有裨益。
编译自:
Breen, M. S., C. Kemena, et al. (2012). "Epistasis as the primary factor in molecular evolution." Nature advance online publication (doi: 10.1038/nature11510 Received 06 March 2012 Accepted 14 August 2012 Published online 14 October 2012: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11510.html).
Epistasis as the primary factor in molecular evolution
The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection1, 2, 3, 4, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.


鑫达医学翻译公司本着“专业、专注、诚信、共赢”的原则,旨在为广大客户提供生物学、医学、药学材料的口译与笔译,业务范围为医学英语翻译病历翻译医学文献翻译药学翻译SCI医学论文翻译以及写作与投稿,宣传册制作,项目申报材料及医疗类中英文网站的建设工作。
联系方式

免费咨询电话:400-6870-112
传真:0531-88956115
地址:山东省济南市高新区舜华路2000号舜泰广场6号楼27层CD区
邮箱: trans@xdtrans.com