Teshima Kosuke M, Innan Hideki
The Graduate University for Advanced Studies, Hayama, Kanagawa 240-0193, Japan.
Genetics. 2008 Mar;178(3):1385-98. doi: 10.1534/genetics.107.082933. Epub 2008 Feb 1.
Neofunctionalization occurs when a neofunctionalized allele is fixed in one of duplicated genes. This is a simple fixation process if duplicated genes accumulate mutations independently. However, the process is very complicated when duplicated genes undergo concerted evolution by gene conversion. Our simulations demonstrate that the process could be described with three distinct stages. First, a newly arisen neofunctionalized allele increases in frequency by selection, but gene conversion prevents its complete fixation. These two factors (selection and gene conversion) that work in opposite directions create an equilibrium, and the time during which the frequency of the neofunctionalized allele drifts around the equilibrium value is called the temporal equilibrium stage. During this temporal equilibrium stage, it is possible that gene conversion is inactivated by mutations, which allow the complete fixation of the neofunctionalized allele. And then, permanent neofunctionalization is achieved. This article develops basic population genetics theories on the process to permanent neofunctionalization under the pressure of gene conversion. We obtain the probability and time that the frequency of a newly arisen neofunctionalized allele reaches the equilibrium value. It is also found that during the temporal equilibrium stage, selection exhibits strong signature in the divergence in the DNA sequences between the duplicated genes. The spatial distribution of the divergence likely has a peak around the site targeted by selection. We provide an analytical expression of the pattern of divergence and apply it to the human red- and green-opsin genes. The theoretical prediction well fits the data when we assume that selection is operating for the two amino acid differences in exon 5, which are believed to account for the major part of the functional difference between the red and green opsins.
新功能化发生在新功能化的等位基因在其中一个复制基因中固定之时。如果复制基因独立积累突变，这是一个简单的固定过程。然而，当复制基因通过基因转换进行协同进化时，这个过程就非常复杂了。我们的模拟表明，这个过程可以用三个不同阶段来描述。首先，一个新出现的新功能化等位基因通过选择增加频率，但基因转换阻止其完全固定。这两个方向相反的因素（选择和基因转换）形成一种平衡，新功能化等位基因频率在平衡值附近波动的时期被称为时间平衡阶段。在这个时间平衡阶段，基因转换有可能因突变而失活，从而使新功能化等位基因完全固定。然后，实现永久新功能化。本文发展了在基因转换压力下达到永久新功能化过程的基本群体遗传学理论。我们得到了新出现的新功能化等位基因频率达到平衡值的概率和时间。还发现，在时间平衡阶段，选择在复制基因之间的DNA序列差异中表现出强烈特征。差异的空间分布可能在选择靶向的位点周围有一个峰值。我们给出了差异模式的解析表达式，并将其应用于人类红视蛋白和绿视蛋白基因。当我们假设选择作用于外显子5中的两个氨基酸差异时，理论预测与数据拟合良好，这两个氨基酸差异被认为是红视蛋白和绿视蛋白功能差异的主要部分。
