线粒体拥有自身的呈环状的双链DNA分子，其复制和转录受到线粒体和核基因的双重调控。线粒体DNA（mtDNA）复制主要存在两种模型，即链置换模型（the strand-displacement model）和链结合模型（the strand-coupled model）。链置换模型认为线粒体复制从特定位点起始，H链先单向复制到mtDNA分子的约2/3位置，使L链复制起始位点暴露，随即引发L链复制；而链结合模型认为线粒体复制从多个位点起始，双链同时双向进行复制。关于线粒体复制模型仍存在一些争论，但这两类复制模型都认为mtDNA中一段长约1kb的非编码序列，即控制区（control region）或称D-环（D-loop）与mtDNA复制密切相关，其中含有很多控制复制的功能元件如复制引物结合位点、复制起始位点、复制终止位点等。在现有mtDNA数据库中，尚未发现正常人D-环区有大片段插入和缺失的情况，这间接说明该区域在mtDNA复制调控中的重要作用。
近期，姚永刚课题组的毕蕊、张阿梅、张文等在对我国人群mtDNA D-环区突变频谱的研究中，在一个正常人家系的mtDNA中意外发现其D-环存在一段50 bp的缺失（m.298_347del50），该缺失导致线粒体保守序列框Ⅱ（CSBⅡ）和线粒体复制起始过程中的引物结合区被移除，而这两个功能单元在以往的研究中被认为与mtDNA的复制起始调控有关。该50 bp缺失在研究的家系母系成员中可以遗传，且在不同的组织样本如头发、血液、唾液等都存在，具有不同程度的异质性。相对于正常对照人群血液细胞的mtDNA拷贝数来说，含有缺失的家系成员的mtDNA拷贝数未见异常，且该家系成员无相关遗传性疾病。这一发现对D-环区的这两个复制功能单元在复制模型中是否必需提出了疑问，提示mtDNA的复制机制可能比以前认为的更为复杂。我们推测该家系成员的mtDNA的复制可能存在其他代偿途径。对此机制的深入研究，将有望进一步认识mtDNA复制的复杂机制。该研究工作近期在线发表于国际知名刊物 Human Mutation。(生物谷Bioon.com)
生物谷推荐原文出处：
Hum Mutat. doi：10.1002/humu.21220
The acquisition of an inheritable 50-bp deletion in the human mtDNA control region does not affect the mtDNA copy number in peripheral blood cells.
Bi R, Zhang AM, Zhang W, Kong QP, Wu BL, Yang XH, Wang D, Zou Y, Zhang YP, Yao YG.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences " Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
The mitochondrial DNA (mtDNA) control region is believed to play an important biological role in mtDNA replication. Large deletions in this region are rarely found, but when they do occur they might be expected to interfere with the replication of the molecule, thus leading to a reduction of mtDNA copy number. During a survey for mtDNA sequence variations in 5,559 individuals from the general Chinese population and 2,538 individuals with medical disorders, we identified a 50-bp deletion (m.298_347del50) in the mtDNA control region in a member of a healthy Han Chinese family belonging to haplogroup B4c1b2, as suggested by complete mtDNA genome sequencing. This deletion removes the conserved sequence block II (CSBII; region 299-315) and the replication primer location (region 317-321). However, quantification of the mtDNA copy number in this subject showed a value within a range that was observed in 20 healthy subjects without the deletion. The deletion was detected in the hair samples of the maternal relatives of the subject and exhibited variable heteroplasmy. Our current observation, together with a recent report for a benign 154-bp deletion in the mtDNA control region, suggests that the control of mtDNA replication may be more complex than we had thought. (c) 2010 Wiley-Liss, Inc.
