Enhanced fixation and preservation of a newly arisen duplicate gene by masking deleterious loss-of-function mutations.
Enhanced fixation and preservation of a newly arisen duplicate gene by masking deleterious loss-of-function mutations.
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DOI：
10.1017/s0016672309000196
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发表时间：
2009-08
影响因子：
1.5
通讯作者：
Kentaro M. Tanaka;K. R. Takahasi;T. Takano-Shimizu
中科院分区：
文献类型：
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作者：
Kentaro M. Tanaka;K. R. Takahasi;T. Takano-Shimizu
片段复制在许多真核生物基因组中非常丰富，其潜在的后果是基因复制。虽然以前对基因复制的理论研究主要集中在固定后的基因沉默过程，但导致固定的过程对片段复制更加重要，因为大多数复制在种群中达到显著频率之前就会丢失。在这里，通过一系列的计算机模拟，我们表明针对功能丧失突变的纯化选择增加了新的重复基因的固定概率，特别是在基因单倍体不足的情况下。理论上，当种群规模(N)、突变的显性程度(H)和重复基因之间的重组率(C)都足够大时(Nu(C)>；1，h>；0.1和c>；u(C))，同时保留两个重复基因的概率是功能丧失突变率(u(C))的两倍。保存率随h迅速下降，当h=0时变为0(单充分性)。我们推断，掩盖有害的功能丧失突变为重复基因提供了直接的选择优势，加上基因剂量增加的影响，将主要决定重复基因在其进化的早期阶段的命运。
Segmental duplications are enriched within many eukaryote genomes, and their potential consequence is gene duplication. While previous theoretical studies of gene duplication have mainly focused on the gene silencing process after fixation, the process leading to fixation is even more important for segmental duplications, because the majority of duplications would be lost before reaching a significant frequency in a population. Here, by a series of computer simulations, we show that purifying selection against loss-of-function mutations increases the fixation probability of a new duplicate gene, especially when the gene is haplo-insufficient. Theoretically, the probability of simultaneous preservation of both duplicate genes becomes twice the loss-of-function mutation rate (u(c)) when the population size (N), the degree of dominance of mutations (h) and the recombination rate between the duplicate genes (c) are all sufficiently large (Nu(c)>1, h>0.1 and c>u(c)). The preservation probability declines rapidly with h and becomes 0 when h=0 (haplo-sufficiency). We infer that masking deleterious loss-of-function mutations give duplicate genes an immediate selective advantage and, together with effects of increased gene dosage, would predominantly determine the fates of the duplicate genes in the early phase of their evolution.