来自英国纽卡斯尔大学的Patrick Chinnery、德国马普学会衰老生物学研究所的Nils-Goran Larsson及其同事发现小鼠发育中的雌性生殖细胞线粒体的异质性水平原则上是由产前决定的,但是随后的分配过程中,线粒体的tRNAMet基因会发生异质性的单碱基对缺失突变。相关的研究论文于10月7日在线发表在《Nature Genetics》期刊上。

-2012年11月《自然-遗传》

中文翻译


【题目】生殖细胞mtDNA的异质性突变由产前决定但会在随后的分配中发生修饰

【译文】在致病性突变的遗传过程中,线粒体DNA(mtDNA)异质性会发生显著性变化,人们试图对此进行解释,但遇到很大的研究障碍,即异质性变化的精确发生时间仍存在争议,也不清楚选择作用是否在其中起作用。这些问题对于准妈妈们的遗传咨询以及针对疾病预防的治疗方法的发展都很重要。通过研究小鼠线粒体tRNAMet基因中遗传的异质单碱基对缺失现象,我们发现哺乳动物线粒体DNA的异质性程度主要是由产前确定的,即在发育中的母性生殖细胞中被确定。尽管没有发现明显的线粒体DNA产前选择的证据,但在下一代的后代中,异质性水平出现偏斜,这与净化选择的作用相一致。若线粒体内存在高水平的tRNAMet发生突变的DNA,全部RNA水平必然会补偿性提高,这就完善了生化表型同时解释了为什么繁殖力不会妥协下降。

英文原稿


[Title]: Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission  

[Authors]: Christoph Freyer, Lynsey M Cree, Arnaud Mourier, James B Stewart, Camilla Koolmeister, Dusanka Milenkovic, Timothy Wai, Vasileios I Floros, Erik Hagström, Emmanouella E Chatzidaki, Rudolf J Wiesner, David C Samuels, Nils-Göran Larsson & Patrick F Chinnery

[Abstract]: A genetic bottleneck explains the marked changes in mitochondrial DNA (mtDNA) heteroplasmy that are observed during the transmission of pathogenic mutations, but the precise timing of these changes remains controversial, and it is not clear whether selection has a role. These issues are important for the genetic counseling of prospective mothers and for the development of treatments aimed at disease prevention. By studying mice transmitting a heteroplasmic single-base-pair deletion in the mitochondrial tRNAMet gene, we show that the extent of mammalian mtDNA heteroplasmy is principally determined prenatally within the developing female germline. Although we saw no evidence of mtDNA selection prenatally, skewed heteroplasmy levels were observed in the offspring of the next generation, consistent with purifying selection. High percentages of mtDNA genomes with the tRNAMet mutation were linked to a compensatory increase in overall mitochondrial RNA levels, ameliorating the biochemical phenotype and explaining why fecundity is not compromised.

原文地址

http://www.nature.com/ng/journal/v44/n11/full/ng.2427.html

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201301/nature-genetics-mtdna-heteroplasmy-trnamet-mutation-purifying-selection/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


+ 一 = 8


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息