Tanaka Kentaro M, Takahasi K Ryo, Takano-Shimizu Toshiyuki
Department of Genetics, Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan.
Genet Res (Camb). 2009 Aug;91(4):267-80. doi: 10.1017/S0016672309000196.
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.
节段性重复在许多真核生物基因组中富集，其潜在后果是基因重复。虽然先前关于基因重复的理论研究主要集中在固定后的基因沉默过程，但对于节段性重复而言，导致固定的过程更为重要，因为大多数重复在种群中达到显著频率之前就会丢失。在这里，通过一系列计算机模拟，我们表明针对功能丧失突变的纯化选择会增加新重复基因的固定概率，特别是当该基因单倍体不足时。从理论上讲，当种群大小（N）、突变的显性程度（h）以及重复基因之间的重组率（c）都足够大（Nu(c)>1，h>0.1且c>u(c)）时，两个重复基因同时保留的概率变为功能丧失突变率（u(c)）的两倍。保留概率随h迅速下降，当h = 0（单倍体充足）时变为0。我们推断，掩盖有害的功能丧失突变会赋予重复基因直接的选择优势，并且与基因剂量增加的效应一起，将在很大程度上决定重复基因在其进化早期阶段的命运。
