NUCLEOTIDE-SEQUENCES OF COMPLEMENTARY DEOXYRIBONUCLEIC ACIDS FOR THE PRO-ALPHA-1 CHAIN OF HUMAN TYPE-I PROCOLLAGEN - STATISTICAL EVALUATION OF STRUCTURES THAT ARE CONSERVED DURING EVOLUTION
NUCLEOTIDE-SEQUENCES OF COMPLEMENTARY DEOXYRIBONUCLEIC ACIDS FOR THE PRO-ALPHA-1 CHAIN OF HUMAN TYPE-I PROCOLLAGEN - STATISTICAL EVALUATION OF STRUCTURES THAT ARE CONSERVED DURING EVOLUTION
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DOI：
10.1021/bi00291a023
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发表时间：
1983-01-01
期刊：
影响因子：
2.9
通讯作者：
PROCKOP, DJ
中科院分区：
文献类型：
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作者：
BERNARD, MP;CHU, ML;PROCKOP, DJ
测定了2个克隆的c[互补]DNA的核苷酸序列，这些c[互补]DNA编码超过3/4的人I型前胶原α1(I)链。与以前公布的I型胶原α1(I)链氨基酸序列的数据进行比较，可以检查该基因转录产物的突变，这些突变发生在人、小牛、大鼠、小鼠和鸡的进化过程中。核苷酸序列与鸡和人的前α2(I)链的相应序列的比较表明，在2.5亿年或更长时间的进化过程中，选择性压力对前α1(I)链的结构的作用比对前α2(I)链的作用更强。为了提高比较的可靠性，对之前评估替换位点和沉默位点突变的程序进行了修改，对核苷酸序列进行了检查。α1(I)链之间替换位点的校正偏差为6.+-。0.8%，15.+-。α2(I)链为1.9%。原α(I)链的C-前肽结构域也高度保守，在替换位点处的校正发散为5.+-。0.9%，该值与先前发现的前α2(I)链的C-前肽的值不能区分。这两种C-前肽的大部分结构似乎都处于选择压力之下。对原α(I)链C-前肽变化的检查表明，在碳水化合物结合部位周围有一个高度保守的区域，类似于先前在原α2(I)链的C-前肽中发现的37个氨基酸的高度保守区域。然而，两个统计检验不能确认前α1(I)链C-前肽变化的非随机分布。同样的测试确定了前α2(I)链的C-前肽的核苷酸变化中存在非随机分布。人I型前胶原蛋白原α1(I)的3‘’非编码区与鸡的同源性不同。对α1(I)链密码子使用的分析表明，在先前为鸡α1(I)链注意到的Gly、Pro和Ala密码子中，U和C具有相同的第3碱基偏好。使用关于人、小鼠和鸡的前α1(I)和前α2(I)基因替换位点的校正分歧的数据来估计自前α1(I)和前α2(I)基因分歧以来的时间。分歧明显发生在950。+-。1.2亿年前。由于这一日期早于后生动物首次出现的几次估计，因此有可能预测阿尔法。在第一个多细胞生物体出现之前，基因就复制了。基于进化时钟假说估计基因复制时间的假设可能不适用于胶原基因。
Nucleotide sequences were determined for 2 cloned c[complementary]DNA encoding for over 3/4 of the pro.alpha.1(I) chain of type I procollagen from man. Comparison with previously published data on amino acid sequences of the .alpha.1(I) chain of type I collagen made it possible to examine mutations in the transcribed products of the gene which have occurred during the evolution of man, calf, rat, mouse and chick. Comparison of the nucleotide sequences with the corresponding sequences of cDNA from chick and with cDNA for the pro.alpha.2(I) chain from man demonstrated that selective pressure during evolution for 250 million or more yr acted more strongly on the structure of the pro.alpha.1(I) chain than on the pro.alpha.2(I) chain. To improve the reliability of the comparison, the nucleotide sequences were examined with a modification of previous procedures for evaluating mutations in replacement sites and silent sites. The corrected divergence for replacement sites between the .alpha.1(I) chains was 6 .+-. 0.8% whereas it was 15 .+-. 1.9% for the .alpha.2(I) chains. The C-propeptide domain of the pro.alpha.(I) chain was also highly conserved with a corrected divergence at replacement sites of 5 .+-. 0.9%, a value that was not distinguishable from the value previously found for the C-propeptide of the pro.alpha.2(I) chain. A large part of the structure of both C-propeptides appears to be under selective pressure. Inspection of changes in the C-propeptide of the pro.alpha.(I) chain suggested that there was a highly conserved region around the carbohydrate attachment site similar to the highly conserved region of 37 amino acids previously found in the C-propeptide of the pro.alpha.2(I) chain. Two statistical tests, however, were unable to confirm nonrandom distribution of changes in the C-propeptide of the pro.alpha.1(I) chain. The same tests established the presence of a nonrandom distribution in nucleotide changes of the C-propeptide of the pro.alpha.2(I) chain. The 3''-noncoding region of the cDNA for pro.alpha.1(I) of human type I procollagen showed no homology with the same region in the chick. Analysis of codon usage for the .alpha.1(I) chain indicated the same 3rd base preference for U and C in codons for Gly, Pro and Ala previously noted for the chick .alpha.1(I) chain. The data on the corrected divergence at replacement sites for the pro.alpha.1(I) and the pro.alpha.2(I) genes in man, mouse and chick were used to estimate the time since the divergence of the pro.alpha.1(I) and the pro.alpha.2(I) genes. The divergence apparently occurred 950 .+-. 120 million yr ago. Since this date precedes several estimates for the 1st appearance of metazoa, it is possible that the pro.alpha. genes duplicated before the 1st multicellular organisms arose. The assumptions for estimating the time of gene duplication based on the evolutionary clock hypothesis may not be valid for collagen genes.