Male-driven Molecular Evolution

在DNA复制错误是导致分子进化的突变的主要来源的假设下，我们发现男性和女性生殖细胞分裂的不同数量导致了常染色体和性染色体之间不同的突变频率。在XX雌性/XY雄性系统中，当生殖细胞分裂数(α)很大时，X染色体的预期突变频率R_&lt；X/A&gt；Y染色体相对于常染色体突变频率R_&lt；Y/A&gt；分别为2/3和2。为了验证这一点，我们比较了人类和小鼠(或大鼠)常染色体和X连锁基因的核苷酸序列，并分析了沉默替代的进化率。X连锁基因相对于常染色体连锁基因的平均沉默替换率(R^‘_)为0.58，接近预期值2/3。对于Y连锁基因的相对进化速率R^’__，我们观察到R^‘=2.2，也接近预期值2。从观察到的R’与α&gt；&gt；1的预期R‘之间的强相关性，我们推测男性可能是一个突变诱发者。我们还发现，在X连锁基因中，假基因进化的速度是功能基因的1.54倍，啮齿动物的进化速度是非啮齿哺乳动物的2.3倍。这些特性在数量上与在常染色体基因中发现的一致，表明整个X染色体区域的突变频率一致降低。ZW女性/ZZ男性系统的相对突变频率与XX/YY系统的相对突变频率相反：对于α&gt；&gt；1，R_&lt；Z/A&gt；(=4/3)&gt；1&gt；&gt；R_&lt；W/A&gt；.预计R_&lt；w/A&gt；的值非常小。对鸟类基因的分析将为这一模型提供明确的证据。

Under the assumption that errors in DNA replication are the major source of mutations that contribute to molecular evolution, we showed that different numbers of germ-cell division between males and females result in different mutation frequencies between autosomes and sex chromosomes. The expected mutation frequency, R_<X/A>, of X chromosome and that, R_<Y/A>, of Y chromosome relative to the mutation frequency of autosomes were shown to be 2/3 and 2 in the XX female/XY male system, respectively, if male to female ratio of the number of germ-cell divisions (alpha) is very large. To test this, we compared nucleotide sequences of autosome- and X-linked genes between human and mouse(or rat) and analyzed the evolutionary rates of silent substitutions. The average rate of silent substitutions of X-linked genes relative to that of autosome-linked genes (R^'_) was shown to be 0.58, being close to the expected value 2/3. For the relative evolutionary rate R^'_ of a Y-linked gene, we observed R^'_=2.2, which again is close to the expected value 2. From the strong correlation between the observed R' and the expected R for alpha>>1, we proposed that males possibly serve as a mutation generator. We also found that, in X-linked genes, the rate of pseudogene evolution is 1.54 times as high as their functional counterpart and rodents evolve at 2.3 times the rate of non-rodent mammals. These properties agree well quantitatively with those found in autosomal genes, suggesting uniformly reduced mutation frequency over the whole X chromosomal regions. The relative mutation frequencies of the ZW female/ZZ male system were shown to be a reversal of those of XX/YY system: For alpha>>1, R_<Z/A>(=4/3)>1>>R_<W/A>. A very small value of R_<w/A> is expected. An analysis of avian genes would provide a clear-cut proof of this model.