Adaptive selection of mitochondrial complex I subunits during primate radiation
Adaptive selection of mitochondrial complex I subunits during primate radiation
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DOI：
10.1016/j.gene.2006.03.015
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发表时间：
2006-08-15
期刊：
影响因子：
3.5
通讯作者：
Wallace, Douglas C.
中科院分区：
文献类型：
--
作者：
Mishmar, Dan;Ruiz-Pesini, Eduardo;Wallace, Douglas C.
哺乳动物氧化磷酸化(OXPHOS)复合体I、III、IV和V由线粒体DNA(MtDNA)和核DNA(NDNA)编码的亚基组成，其中复合体I由39个nDNA和7个mtDNA亚基组成。然而，线粒体DNA基因的序列变异比OXPHOS复合体的nDNA编码基因大10倍以上，mtDNA蛋白被发现受到正(适应性)选择的影响。为了维持功能复合体I，nDNA和mtDNA亚基必须相互作用，这意味着某些nDNA复合体I基因也可能受到正选择的影响。为了确定正选择是否影响了nDNA复合体I基因，我们分析了猩猩、大猩猩、黑猩猩、人类和所有可用脊椎动物的所有nDNA和mtDNA编码复合体I亚基的DNA序列。这表明3个nDNA复合体I基因(NDUFC2、NDUFA1和NDUFA4)在PAML和Z检验中都显著提高了氨基酸替换率，表明它们在灵长类辐射过程中受到了适应性选择。由于这三个亚基都与mtDNA亚基一起位于复合体I的膜区，所以我们比较了这三个nDNA基因和mtDNA基因在不同物种中的氨基酸变化。NDNA NDUFC2半胱氨酸39的变化与mtDNA ND5半胱氨酸330的变化相关。因此，适应性选择已经影响了一些nDNA复合体I基因，nDNA和mtDNA复合体I基因可能是共同进化的。(C)2006爱思唯尔B.V.保留所有权利。
Mammalian oxidative phosphorylation (OXPHOS) complexes I, III, IV and V are assembled from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) encoded subunits, with complex I encompassing 39 nDNA and seven mtDNA subunits. Yet the sequence variation of the mtDNA genes is more than ten fold greater than that of the nDNA encoded genes of the OXPHOS complexes and the mtDNA proteins have been found to be influenced by positive (adaptive) selection. To maintain a functional complex I, nDNA and mtDNA subunits must interact, implying that certain nDNA complex I genes may also have been influenced by positive selection. To determine if positive selection has influenced nDNA complex I genes, we analyzed the DNA sequences of all of the nDNA and mtDNA encoded complex I subunits from orangutan, gorilla, chimpanzee, human and all available vertebrate sequences. This revealed that three nDNA complex I genes (NDUFC2, NDUFA1, and NDUFA4) had significantly increased amino acid substitution rates by both PAML and Z-test, suggesting that they have been subjected to adaptive selection during primate radiation. Since all three of these subunits reside in the membrane domain of complex I along with the mtDNA subunits, we compared amino acid changes in these three nDNA genes with those of the mtDNA genes across species. Changes in the nDNA NDUFC2 cysteine 39 were found to correlate with those in the mtDNA ND5 cysteine 330. Therefore, adaptive selection has influenced some nDNA complex I genes and nDNA and mtDNA complex I genes may have co-evolved. (c) 2006 Elsevier B.V. All rights reserved.