Perler F, Efstratiadis A, Lomedico P, Gilbert W, Kolodner R, Dodgson J
Cell. 1980 Jun;20(2):555-66. doi: 10.1016/0092-8674(80)90641-8.
We have characterized a clone carrying a chicken preproinsulin gene, which is present in only one copy in the chicken genome. The gene contains two introns: a 3.5 kb intron interrupting the region encoding the connecting peptide and a 119 bp intron interrupting the DNA corresponding to the 5' non-coding region of the mRNA. This is similar to the structure of rat insulin gene II; therefore it represents the common ancestor. Since the rat insulin gene I lacks a 499 bp intron in the coding region, the rat genes have evolved by a recent gene duplication followed by loss of this intron in one copy. The divergences between insulin gene sequences, and also between globin genes, show that changes at introns and silent positions in coding regions appear very rapidly (7 X 10(-9) substitutions per nucleotide site per year), but that the accumulation of changes in these sites saturates, although not completely, after about 100 million years. From this we conclude that not all of these sites are neutral and that they do not behave as accurate evolutionary clocks over long periods of time. However, nucleotide substitutions leading to amino acid replacements are an excellent clock. Our analysis indicates that this clock is driven by selection.
我们已鉴定出一个携带鸡前胰岛素原基因的克隆，该基因在鸡基因组中仅以单拷贝形式存在。该基因包含两个内含子：一个3.5 kb的内含子打断了编码连接肽的区域，另一个119 bp的内含子打断了与mRNA 5'非编码区相对应的DNA。这与大鼠胰岛素基因II的结构相似；因此它代表了共同祖先。由于大鼠胰岛素基因I在编码区缺少一个499 bp的内含子，大鼠的这些基因是通过近期的基因复制，随后其中一个拷贝丢失该内含子而进化而来的。胰岛素基因序列之间以及珠蛋白基因之间的差异表明，内含子和编码区沉默位点的变化出现得非常迅速（每年每个核苷酸位点有7×10⁻⁹个替换），但这些位点变化的积累在大约1亿年后虽然没有完全饱和，但也趋于平稳。由此我们得出结论，并非所有这些位点都是中性的，并且它们在长时间内并不表现为精确的进化时钟。然而，导致氨基酸替换的核苷酸替换是一个很好的时钟。我们的分析表明，这个时钟是由选择驱动的。
