PROTEOMICS AND COMPARATIVE GENOMIC INVESTIGATIONS REVEAL HETEROGENEITY IN EVOLUT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 男性的生殖能力受到精液的强烈影响。除了与女性环境相互作用外，精液还调节精子的重要生理特征，包括获能和运动能力。在哺乳动物中，男性生殖道显示出惊人的区隔程度，至少有六种不同的组织类型贡献了与精子结合在一起的射精物质。虽然已经在一些物种中进行了对整个射精的研究，但我们缺乏不同附属组织产生的特定蛋白质的全面图像。在这里，我们对小鼠雄性生殖道的六个区域-精囊、前前列腺、背外侧前列腺、腹侧前列腺、球状尿道腺和球状尿路憩室进行了蛋白质组学研究。我们确定了可能被定位到506个独特基因的766个蛋白质，并将它们与高质量的人类精液数据集进行比较。我们发现精液蛋白的基因本体论功能在小鼠和人类之间很大程度上是保守的。通过将这些数据置于进化框架中，我们表明与基因组相比，精囊蛋白经历了显著更高的非同义替换率，这可能是适应性进化的结果。相比之下，来自其他五个组织的蛋白质显示出显著较低的非同义替代，揭示了以前没有意识到的对大多数男性生殖蛋白质的进化限制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Male reproductive fitness is strongly affected by seminal fluid. In addition to interacting with the female environment, seminal fluid mediates important physiological characteristics of sperm, including capacitation and motility. In mammals, the male reproductive tract shows a striking degree of compartmentalization, with at least six distinct tissue types contributing material that is combined with sperm in an ejaculate. While studies of whole ejaculates have been undertaken in some species, we lack a comprehensive picture of the specific proteins produced by different accessory tissues. Here we perform proteomic investigations of six regions of the male reproductive tract in mice - seminal vesicles, anterior prostate, dorsolateral prostate, ventral prostate, bulbourethral gland, and bulbourethral diverticulum. We identify 766 proteins that could be mapped to 506 unique genes and compare them to a high-quality human seminal fluid dataset. We find that Gene Ontology functions of seminal proteins are largely conserved between mice and humans. By placing these data in an evolutionary framework, we show that seminal vesicle proteins have experienced a significantly higher rate of nonsynonymous substitution compared to the genome, which could be the result of adaptive evolution. In contrast, proteins from the other five tissues showed significantly lower nonsynonymous substitution, revealing a previously unappreciated level of evolutionary constraint acting on the majority of male reproductive proteins.