# Molecular basis of adaptation of seminal proteins of humans and other primates

> **NIH NIH R15** · DUQUESNE UNIVERSITY · 2020 · $6,685

## Abstract

Note: This Project Summary is repeated from the parent grant, but with bold highlighting to
indicate the portion of the research the undergraduate student, Thomas Washington, will be
working on under the proposed Supplement to Promote Diversity in Health-related Research.
Project Summary
The >20,000 protein-coding genes in our body have been shaped by the combined forces of
mutation, natural selection, genetic drift, and migration. An essential way to understand the
effects of these forces, especially the consequences of individual amino acid-changing
mutations on protein function, is to compare our genes and proteins to those of our closest
relatives. In doing so, the mode of selection (positive selection, negative selection, or relaxation
of constraint) can also be inferred. Over the last decade, over a dozen high-quality primate
genome sequences have been published, allowing for detailed investigation of the forces of
evolution acting on the human genome and the genomes of other hominids, using complex
models based on the principles of population genetics and molecular evolution. In the proposed
research, we will go beyond computational predictions of selection by performing quantitative
functional assays using recombinant proteins and synthetic peptides to measure differences in
catalytic efficiency and substrate specificity of high-abundant extracellular proteins found in
human semen. Such proteins have often been predicted computationally to be the targets of
positive selection, purifying selection, and pseudogenization among the hominid primates
(humans and the great apes).
The experimental design will include testing the function of recombinant proteins from humans,
chimpanzees, gorillas, and macaques. Furthermore, we will create the proteins corresponding
to the last common ancestors of humans and chimpanzees; of humans, chimpanzees, and
gorillas; and of macaques and the hominids, using ancestral sequence reconstruction. For each
of these species, we will measure the phosphatase and peptidase activity of the prostatic acid
phosphatase ACPP, the protease activity of the prostate expressed KLK3, and the
transglutaminase activity of prostatic TGM4. Furthermore, the efficiency and specificity each
of these enzymes will be tested using their natural substrates, the seminal vesicle
expressed SEMG1 and SEMG2, to understand their coevolution. In addition to examining
differences among species in enzyme activity, we will test the hypothesis that species differ in
the ability of small peptides derived from ACPP, SEMG1, and SEMG2 to form amyloid fibrils
and enhance HIV infection. Finally, we will use bioinformatics approaches to identify primate
genes whose evolution may have been driven by either sexual selection or resistance to
sexually transmitted viruses.
This research will improve undergraduate education at Duquesne University by exposing
students to meritorious research while significantly enhancing the research environment of the
PI’s labor...

## Key facts

- **NIH application ID:** 10117794
- **Project number:** 3R15GM123447-01S1
- **Recipient organization:** DUQUESNE UNIVERSITY
- **Principal Investigator:** Michael Ignatius Jensen-Seaman
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $6,685
- **Award type:** 3
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117794

## Citation

> US National Institutes of Health, RePORTER application 10117794, Molecular basis of adaptation of seminal proteins of humans and other primates (3R15GM123447-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10117794. Licensed CC0.

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