EVOLUTIONARY SIMILARITIES BETWEEN PANCREATIC PROTEOLYTIC ENZYMES
EVOLUTIONARY SIMILARITIES BETWEEN PANCREATIC PROTEOLYTIC ENZYMES
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DOI：
10.1038/2071157a0
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发表时间：
1965-01-01
期刊：
影响因子：
64.8
通讯作者：
SMILLIE, LB
中科院分区：
文献类型：
--
作者：
HARTLEY, BS;BROWN, JR;SMILLIE, LB
现在人们普遍认为，蛋白质的氨基酸序列是由其亲本基因的核苷酸序列决定的，因此，比较相关蛋白质的序列可以为它们的遗传起源提供线索。如果我们比较来自不同物种的相似蛋白质，我们可能希望追踪物种的进化关系，因为在种群中建立的可行突变将具有进化稳定性，并且可以作为识别家族同源性的标记。胰岛素、血红蛋白和细胞色素C的种属差异比较为此类研究奠定了基础。然而，另一种方法是比较来自同一物种或个体的不同蛋白质。这些不同蛋白质的氨基酸序列之间的相当大的同源性可能表明一个共同的进化祖先。例如，某些哺乳动物肽酶和酯酶的区别在于它们在活性中心的独特丝氨酸残基处与氟磷酸二异丙酯（DFP）反应的能力。在所有这些酶中，直接围绕这个活性丝氨酸残基的氨基酸序列非常相似。一种假设是，这些蛋白质可能是由一些共同的祖先基因的增殖产生的，随后是独立的突变，以允许序列的分歧，并最终导致酶的特异性。因此，它们氨基酸序列的同源性反映了它们共同祖先的痕迹。或者，这些丝氨酸酶的活性中心序列的相似性可能仅仅代表催化活性所必需的结构。在这种情况下，它们可能是通过不同起源基因的趋同进化而产生的。只有当发现序列的同源性非常广泛时，才能消除这种假设。胰蛋白酶和糜蛋白酶A的序列同源性。最近对牛胰凝乳蛋白酶原A（参考文献2）的完整氨基酸序列和几乎所有胰蛋白酶原序列的测定支持了一个共同进化祖先的假设。观察到从这些蛋白质的部分酸水解产物中获得的一些肽的比较最初表明相当大的同源性是有益的，但是进一步的研究倾向于将这种同源性的意义最小化。现地址：魏茨曼大学生物物理学系
T is now generally agreed that the amino-acid sequence of a protein is determined by the nucleotide sequence of its parent gene, so that comparison of the sequences of related proteins can provide clues about their genetic origins. If we compare similar proteins from different species we may hope to trace the evolutionary relationship of the species, since viable mutations which become established in a population will have evolutionary stability, and can act as markers to identify familial resemblances. Comparison of species differences in insulin, haemoglobin and cytochrome C have laid the foundation for such studies. However, an alternative approach is to compare different proteins from the same species or individual. Considerable homologies between the amino-acid sequences of these different proteins might indicate a common evolutionary ancestor. For example, certain mammalian peptidases and esterases are distinguished by their capacity to react with diisopropyl phosphorofluoridate (DFP) at a unique serine residue in the active centre. The aminoacid sequence immediately surrounding this active serine residue is remarkably similar in all these enzymes. One hypothesis is that these proteins may have arisen by multiplication of some common ancestral gene, followed by independent mutations to allow divergence of sequence and ultimately of enzymatic specificity. Homologies in their amino-acid sequences would therefore reflect the vestiges of their common ancestor. Alternatively, the similarities in active centre sequence of these serine enzymes might merely represent structures essential for the catalytic activity. In this case they could arise by convergent evolution from genes of different origin. Only if the homologies of sequence were found to be very extensive could this hypothesis be eliminated. Seguence homologies in trypsin and chymotrypsin A. Recent determinations of the complete amino-acid sequence of bovine chymotrypsinogen A (ref. 2) and almost all the sequence of trypsinogen" have lent support to the hypothesis of a common evolutionary ancestor. It is instructive to observe that comparison of a few peptides from partial acid hydrolysates of these proteins had originally indicated considerable homclogy “, but further investigation tended to minimize the significance of this*".* Present address: Tepartment of Biophysics, Weizmann Institute of