Phylogeographic analysis of mitochondrial DNA haplogroup F2 in China reveals T12338C in the initiation codon of the ND5 gene not to be pathogenic.
In this report, we studied on a homoplasmic T12338C change in mitochondrial DNA (mtDNA), which substituted methionine in the translational initiation codon of the NADH dehydrogenase subunit 5 gene ( ND5) with threonine. This nucleotide change was originally identified in two mtDNAs belonging to haplogroup F2 by our previous complete sequencing of 48 mtDNAs. Since then, a total of 76 F2 mtDNAs have been identified by the variations occurring in the hypervariable segments and coding regions among more than 3,000 individuals across China. As the T12338C change was detected in 32 samples representing various sub-clades of the F2 haplogroup while not in 14 non-F2 controls, we believe that the T12338C change is specific to the F2 haplogroup. As F2 and its sub-clades were widely distributed in normal individuals of various Chinese populations, we conclude that T12338C is not pathogenic. In addition, based on the average distribution frequency, haplotype diversity and nucleotide diversity of haplogroup F2 in the populations across China, the T12338C nucleotide substitution seems to have been occurred in north China about 42,000 years ago. Our results provided a good paradigm for distinguishing a polymorphic change from a pathogenic mutation based on mtDNA phylogeny.
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.|Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming, 650091, China.|Graduate School of the Chinese Academy of Sciences, Beijing, 100039, China.
Qing-Peng
QP
Kong
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.|The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Yong-Gang
YG
Yao
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.|Graduate School of the Chinese Academy of Sciences, Beijing, 100039, China.
Chang
C
Sun
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Chun-Ling
CL
Zhu
Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming, 650091, China.
Li
L
Zhong
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.|Graduate School of the Chinese Academy of Sciences, Beijing, 100039, China.
Cheng-Ye
CY
Wang
Department of Biochemistry, Hainan Medical College, Haikou, 571101, China.
Wang-Wei
WW
Cai
Department of Medical Genetics, First Military Medical University, Guangzhou, 510515, China.
Xiang-Min
XM
Xu
College of Life Sciences, Zhongshan University, Guangzhou, 510275, China.
An-Long
AL
Xu
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China. zhangyp1@263.net.cn.|Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming, 650091, China. zhangyp1@263.net.cn.
Ya-Ping
YP
Zhang
D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D002681:China; D018387:Codon, Initiator / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000145:classification / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008715:Methionine / Q000235:genetics; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010802:Phylogeny; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013912:Threonine / Q000235:genetics
D018387:Codon, Initiator; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D013912:Threonine; D008715:Methionine; C481838:MT-ND5 protein, human; D042967:Electron Transport Complex I