Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyev Ave, Novosibirsk, 630090, Russia.
Novosibirsk State University, 1, Pirogova str., Novosibirsk, 630090, Russia.
BMC Genet. 2020 Oct 22;21(Suppl 1):89. doi: 10.1186/s12863-020-00896-6.
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.
在种群生态学中，生殖潜能的概念表示在最佳条件下产生和维持健康后代直至其生殖成熟的最关键指标。这个概念将个体的生活质量和寿命与他/她基因组编码的疾病易感性联系起来。过去，人们已经深入、广泛和全面地研究了女性生殖潜能，但男性生殖潜能并没有得到同等的关注。因此，我们在这里关注人类的 Y 染色体，并找到了男性生殖潜能的候选单核苷酸多态性 (SNP) 标记物。
通过对所有 63 个 Y 连锁基因近端启动子内的 1206 个未注释 SNP 进行计算机分析（即使用我们之前创建的 Web 服务 SNP_TATA_Z-tester），我们发现了 261 个可能的男性生殖潜能 SNP 标记物，这些标记物可以显著改变 TATA 结合蛋白 (TBP) 与这些启动子的结合亲和力。其中，有一些与精子发生障碍（例如 rs1402972626）、儿科癌症（例如 rs1483581212）以及男性焦虑症损害家庭关系和母婴健康（例如 rs187456378）相关的候选 SNP 标记物。首先，我们选择性地在体外验证了分析的 TBP-启动子亲和力的绝对值和相对值，其预测值和实测值之间的 Pearson 相关系数分别为 r = 0.84（显著性 p < 0.025）和 r = 0.98（p < 0.025）。接下来，我们发现相对于增加 TBP-启动子亲和力的候选 SNP 标记物，降低其亲和力的标记物数量要少两倍，而在全基因组范围内，SNP 诱导的 TBP-启动子复合物损伤的频率是 SNP 诱导改善的四倍（p < 0.05，二项分布）。这意味着自然选择不利于这些基因的低表达。同时，候选 SNP 标记物增加和减少男性生殖潜能的数量彼此相等（p < 0.05），就好像男性的自我驯化可能已经发生了一样，而这种自我驯化伴随着已知的破坏性自然选择。由于还没有足够的科学证据表明这可能已经发生，我们讨论了与男性生殖潜能的候选 SNP 标记物相关的人类疾病，这些疾病可能与宠物的驯化相关障碍相对应。
总的来说，我们的研究结果似乎支持了一种自我驯化综合征，其中男性生殖潜能的破坏性自然选择阻止了 Y 连锁基因的低表达蛋白。
