Mrnjavac Andrea, Vicoso Beatriz, Connallon Tim
Institute of Science and Technology Austria, Klosterneuburg, Austria.
School of Biological Sciences, Monash University, Clayton, VIC, Australia.
Mol Biol Evol. 2025 Jul 30;42(8). doi: 10.1093/molbev/msaf177.
The first influential hypothesis for sex chromosome evolution was proposed in 1914 by H. J. Muller, who argued that once recombination was suppressed between the X and Y chromosomes, Y-linked genes become "sheltered" from selection, leading to accumulation of recessive loss-of-function (LOF) mutations and decay of Y-linked genes. The hypothesis fell out of favor in the 1970s because early mathematical models failed to support it and data on the dominance of lethal mutations were viewed as incompatible with the hypothesis. We reevaluate the main arguments against Muller's hypothesis and find that they do not conclusively exclude a role for sheltering in sex chromosome evolution. By relaxing restrictive assumptions of earlier models, we show that sheltering promotes fixation of LOF mutations with sexually dimorphic fitness effects, resulting in decay of X-linked genes that are exclusively expressed by males and Y-linked genes that are primarily, though not necessarily exclusively, expressed by females. We further show that drift and other processes contributing to Y degeneration (i.e. selective interference and regulatory evolution) expand conditions of Y-linked gene loss by sheltering. The actual contribution of sheltering to sex chromosome evolution hinges upon the distribution of dominance and sex-specific fitness effects of LOF mutations, which we discuss.
1914年，H. J. 穆勒提出了第一个关于性染色体进化的有影响力的假说。他认为，一旦X和Y染色体之间的重组受到抑制，Y连锁基因就会受到选择的“庇护”，导致隐性功能丧失（LOF）突变的积累以及Y连锁基因的衰退。该假说在20世纪70年代失宠，因为早期的数学模型未能支持它，而且关于致死突变优势的数据被认为与该假说不相符。我们重新评估了反对穆勒假说的主要论点，发现它们并没有确凿地排除“庇护”在性染色体进化中的作用。通过放宽早期模型的限制性假设，我们表明“庇护”促进了具有两性异形适合度效应的LOF突变的固定，导致仅由雄性表达的X连锁基因以及主要（但不一定完全）由雌性表达的Y连锁基因的衰退。我们进一步表明，遗传漂变和其他导致Y退化的过程（即选择性干扰和调控进化）通过“庇护”扩大了Y连锁基因丢失的条件。“庇护”对性染色体进化的实际贡献取决于LOF突变的显性分布和性别特异性适合度效应，我们对此进行了讨论。
