PROTEOMICS AND COMPARATIVE GENOMIC INVESTIGATIONS REVEAL HETEROGENEITY IN EVOLUT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 男性生殖健康受到精液的强烈影响。除了与雌性环境相互作用外，精液还介导精子的重要生理特征，包括获能和运动。在哺乳动物中，雄性生殖道显示出惊人的区域化程度，至少有六种不同的组织类型提供与精液中精子结合的物质。虽然在某些物种中已经进行了整个射精的研究，但我们缺乏对不同附属组织产生的特定蛋白质的全面了解。在这里，我们进行蛋白质组学研究的六个地区的男性生殖道小鼠-精囊，前列腺前，背外侧前列腺，腹侧前列腺，尿道球腺，尿道球憩室。我们确定了766种蛋白质，可以映射到506个独特的基因，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。通过将这些数据放在一个进化的框架中，我们发现，与基因组相比，精囊蛋白经历了显着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，从其他五个组织的蛋白质表现出显着较低的非同义取代，揭示了以前不受重视的水平的进化约束作用于大多数男性生殖蛋白。

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.