Defense Date

11-15-2023

Graduation Date

Spring 5-10-2024

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Biological Sciences

School

School of Science and Engineering

Committee Chair

Michael I. Jensen-Seaman

Committee Member

Jana Patton-Vogt

Committee Member

Jan Janecka

Committee Member

Michael Cascio

Keywords

Primate, Molecular evolution, Sexual selection, Sperm competition, Seminal proteins, KLK3/PSA, Enzymatic activity, HIV/SIV

Abstract

Male reproductive protein-coding genes are among the most rapidly evolving genes across many animal taxa, commonly attributed to sexual selection; however, pathogen defense mechanisms might also be contributing factors. This study aimed to both computationally and experimentally investigate the selective pressures responsible for the rapid evolution of seminal proteins. In the first part, the research focused on sexual selection in the form of post-copulatory sperm competition as a driving force behind the evolution of kallikrein related peptidase 3 (KLK3), also known as prostate-specific antigen (PSA), a key prostatic seminal protein. KLK3 is responsible for the liquefaction of semen coagulum through the hydrolysis of semenogelins, facilitating sperm motility for fertilization. Computational selection models did not confirm any correlation between higher sperm competition and an increased number of nonsynonymous substitutions in KLK3. However, functional studies using recombinant proteins from six primates, including a hypothetical human-chimpanzee ancestor, revealed significant differences in protease activity among KLK3 homologs, indicating sexual selection's role in KLK3 evolution. Quantitative enzymatic activity displayed the possible effects of positive selection in polygynandrous chimpanzees and relaxed constraint in gorillas and gibbons, both experiencing low levels of sperm competition. The second part of the study explored whether seminal proteins have been evolving in response to sexually transmitted viruses like human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV). Computational analyses on prostatic acid phosphatase 3 (ACP3) and both semenogelins (SEMG1 and SEMG2) did not support the rapid adaptive evolution of these proteins in nonhuman primates naturally harboring SIV. However, empirical testing of amyloid fibrils derived from these proteins showed consistent decreased HIV infectivity in chimpanzees. Considering the evidence of sequence-based positive selection observed in chimpanzees, defense mechanisms against sexually transmitted viruses, like SIV, might be playing a role in the evolution of several seminal proteins in species with a long history of SIV. Overall, this study highlighted the dual influences of sexual selection driven by sperm competition and natural selections mediated by pathogen defense mechanisms on the evolution of male reproductive proteins. It also emphasized the importance of combining computational tools with functional approaches to better understand genotype-phenotype interactions in the field of molecular evolution.

Language

English

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