A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications
A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications
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DOI：
10.1016/j.tig.2004.05.001
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发表时间：
2004-07-01
影响因子：
11.4
通讯作者：
Koonin, EV
中科院分区：
文献类型：
--
作者：
Kondrashov, FA;Koonin, EV
野生型等位基因的显性和有害突变等位基因的隐性可能是通过自然选择进化而来的，也可能是基因作用的分子和生理机制的副产品。我们比较了人类单倍充足基因的性质，其野生型等位基因对功能丧失等位基因是显性的，单倍不足（隐性野生型）基因，当杂合功能丧失等位基因时产生异常表型。在编码酶的基因中，单倍足基因的比例最高，这与生理学理论最相符。平均而言，单倍不足的基因比单倍充足的基因具有更多的旁系同源物，这支持了基因剂量对于重复的初始固定可能很重要的观点。因此，一个基因的单倍（不）充分性和它的复制倾向可能有一个共同的进化基础。
The dominance of wild-type alleles and the concomitant recessivity of deleterious mutant alleles might have evolved by natural selection or could be a by-product of the molecular and physiological mechanisms of gene action. We compared the properties of human haplosufficient genes, whose wild-type alleles are dominant over loss-of-function alleles, with haploinsufficient (recessive wild-type) genes, which produce an abnormal phenotype when heterozygous for a loss-of-function allele. The fraction of haplosufficient genes is the highest among the genes that encode enzymes, which is best compatible with the physiological theory. Haploinsufficient genes, on average, have more paralogs than haplosufficient genes, supporting the idea that gene dosage could be important for the initial fixation of duplications. Thus, haplo(in)sufficiency of a gene and its propensity for duplication might have a common evolutionary basis.