Comeron J M, Kreitman M
Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA.
Genetics. 2000 Nov;156(3):1175-90. doi: 10.1093/genetics/156.3.1175.
Intron length is negatively correlated with recombination in both Drosophila melanogaster and humans. This correlation is not likely to be the result of mutational processes alone: evolutionary analysis of intron length polymorphism in D. melanogaster reveals equivalent ratios of deletion to insertion in regions of high and low recombination. The polymorphism data do reveal, however, an excess of deletions relative to insertions (i.e., a deletion bias), with an overall deletion-to-insertion events ratio of 1.35. We propose two types of selection favoring longer intron lengths. First, the natural mutational bias toward deletion must be opposed by strong selection in very short introns to maintain the minimum intron length needed for the intron splicing reaction. Second, selection will favor insertions in introns that increase recombination between mutations under the influence of selection in adjacent exons. Mutations that increase recombination, even slightly, will be selectively favored because they reduce interference among selected mutations. Interference selection acting on intron length mutations must be very weak, as indicated by frequency spectrum analysis of Drosophila intron length polymorphism, making the equilibrium for intron length sensitive to changes in the recombinational environment and population size. One consequence of this sensitivity is that the advantage of longer introns is expected to decrease inversely with the rate of recombination, thus leading to a negative correlation between intron length and recombination rate. Also in accord with this model, intron length differs between closely related Drosophila species, with the longest variant present more often in D. melanogaster than in D. simulans. We suggest that the study of the proposed dynamic model, taking into account interference among selected sites, might shed light on many aspects of the comparative biology of genome sizes including the C value paradox.
在黑腹果蝇和人类中,内含子长度与重组呈负相关。这种相关性不太可能仅是突变过程的结果:对黑腹果蝇内含子长度多态性的进化分析表明,在高重组区和低重组区,缺失与插入的比例相当。然而,多态性数据确实显示,相对于插入而言,缺失过多(即缺失偏向),总体缺失与插入事件的比例为1.35。我们提出了两种有利于较长内含子长度的选择类型。首先,在非常短的内含子中,自然的缺失突变偏向必须被强烈的选择所抵消,以维持内含子剪接反应所需的最小内含子长度。其次,选择将有利于在内含子中发生插入,这些插入会在相邻外显子选择的影响下增加突变之间的重组。即使略微增加重组的突变也将受到选择青睐,因为它们减少了被选择突变之间的干扰。对果蝇内含子长度多态性的频谱分析表明,作用于内含子长度突变的干扰选择一定非常弱,这使得内含子长度的平衡对重组环境和种群大小的变化很敏感。这种敏感性的一个后果是,较长内含子的优势预计会随着重组率的增加而反向降低,从而导致内含子长度与重组率之间呈负相关。同样符合该模型的是,在亲缘关系密切的果蝇物种之间,内含子长度存在差异,最长的变体在黑腹果蝇中出现的频率比在拟暗果蝇中更高。我们认为,考虑到被选择位点之间的干扰,对所提出的动态模型进行研究,可能会为基因组大小比较生物学的许多方面提供启示,包括C值悖论。