In population ecology, the concept of reproductive potential denotes the most vital indicator of chances to produce and sustain a healthy descendant until his/her reproductive maturity under the best conditions. This concept links quality of life and longevity of an individual with disease susceptibilities encoded by his/her genome. Female reproductive potential has been investigated deeply, widely, and comprehensively in the past, but the male one has not received an equal amount of attention. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of male reproductive potential. Examining in silico (i.e., using our earlier created Web-service SNP_TATA_Z-tester) all 1206 unannotated SNPs within 70 bp proximal promoters of all 63 Y-linked genes, we found 261 possible male-reproductive-potential SNP markers that can significantly alter the binding affinity of TATA-binding protein (TBP) for these promoters. Among them, there are candidate SNP markers of spermatogenesis disorders (e.g., rs1402972626), pediatric cancer (e.g., rs1483581212) as well as male anxiety damaging family relationships and mother’s and children’s health (e.g., rs187456378). First of all, we selectively verified in vitro both absolute and relative values of the analyzed TBP–promoter affinity, whose Pearson’s coefficients of correlation between predicted and measured values were r = 0.84 (significance p < 0.025) and r = 0.98 (p < 0.025), respectively. Next, we found that there are twofold fewer candidate SNP markers decreasing TBP–promoter affinity relative to those increasing it, whereas in the genome-wide norm, SNP-induced damage to TBP–promoter complexes is fourfold more frequent than SNP-induced improvement (p < 0.05, binomial distribution). This means natural selection against underexpression of these genes. Meanwhile, the numbers of candidate SNP markers of an increase and decrease in male reproductive potential were indistinguishably equal to each other (p < 0.05) as if male self-domestication could have happened, with its experimentally known disruptive natural selection. Because there is still not enough scientific evidence that this could have happened, we discuss the human diseases associated with candidate SNP markers of male reproductive potential that may correspond to domestication-related disorders in pets. Overall, our findings seem to support a self-domestication syndrome with disruptive natural selection by male reproductive potential preventing Y-linked underexpression of a protein.

中文翻译：

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雄性生殖潜能的破坏性自然选择可防止人Y染色体上的蛋白质编码基因表达不足，从而成为自我驯化综合征

在种群生态学中，生殖潜力的概念是在最佳条件下产生和维持健康后代直至其成熟的机会的最重要指标。这个概念将一个人的生活质量和寿命与他/她的基因组编码的疾病易感性联系起来。过去，已经对女性生殖潜能进行了深入，广泛和全面的研究，但是男性并未受到同等关注。因此，在这里，我们重点研究人的Y染色体，并发现了具有雄性生殖潜力的候选单核苷酸多态性（SNP）标记。在计算机上检查（即使用我们先前创建的Web服务SNP_TATA_Z-tester）所有63个Y连锁基因的70 bp近端启动子中的所有1206个未注释的SNP，我们发现了261种可能的男性生殖潜能SNP标记，这些标记可以显着改变TATA结合蛋白（TBP）对这些启动子的结合亲和力。其中，存在精子发生障碍（例如，rs1402972626），小儿癌症（例如，rs1483581212）以及破坏男性焦虑症的家庭关系以及母亲和儿童的健康状况（例如，rs187456378）的候选SNP标记。首先，我们在体外选择性地验证了所分析的TBP-启动子亲和力的绝对值和相对值，其预测值和测量值之间的皮尔逊相关系数为r = 0.84（显着性p <0.025）和r = 0.98（p <0.025） ）， 分别。接下来，我们发现降低TBP-启动子亲和力的候选SNP标记相对于那些增加它的候选SNP标记要少两倍，而在全基因组范围内，SNP诱导的TBP-启动子复合物损伤的发生频率是SNP诱导的改善的四倍（p <0.05，二项分布）。这意味着针对这些基因表达不足的自然选择。同时，雄性生殖潜力增加和减少的候选SNP标记数彼此之间几乎没有区别（p <0.05），就好像雄性自我驯化可能发生一样，它具有实验上已知的破坏性自然选择。因为仍然没有足够的科学证据证明这可能发生，所以我们讨论了与男性生殖潜能的候选SNP标记有关的人类疾病，这可能与宠物的驯养相关疾病有关。总体，