Invited Speaker Abstract Submission
Harmit S. Malik, Ph.D.
Professor & HHMI Investigator
Fred Hutchinson Cancer Center
Seattle, Washington, United States
Many animal species replace histones with protamines or sperm nuclear basic proteins (SNBPs) during spermatogenesis to more tightly package sperm genomes. Protamines vary across animal lineages and evolve rapidly in mammals. Despite their importance for male fertility, protamines rapidly evolve in many species; the biological causes behind their rapid evolution remain unknown. We investigated the causes underlying this unexpected rapid evolution using a combination of computational and genetic approaches. First, we used a phylogenomic approach to investigate protamine diversification in Drosophila species. We found that most of the ~15 protamine genes in Drosophila melanogaster evolve under positive selection. Unexpectedly, evolutionarily young SNBP genes are more likely to be critical for fertility than ancient, conserved protamine genes. For example, the Drosophila CG30056 protamine gene is dispensable for male fertility despite being one of three protamine genes universally retained across Drosophila species. We found multiple independent protamine gene amplification events that occurred preferentially on sex chromosomes. Conversely, the montium group of Drosophila species lost otherwise-conserved protamine genes, coincident with an X-Y chromosomal fusion. Based on these findings, we hypothesized that autosomal protamine genes suppress meiotic drive, whereas sex-chromosomal protamine expansions lead to meiotic drive. X-Y fusions in the montium group render some autosomal protamines dispensable by making X-versus-Y meiotic drive obsolete or costly. Thus, we hypothesized that genetic conflicts between sex chromosomes may drive the rapid evolution of protamines during spermatogenesis in Drosophila species. In a second stage, using an in vivo gene replacement strategy, we investigate the causes behind the rapid evolution of protamine Mst77F, which is essential for male fertility in D. melanogaster. Increasing divergence of Mst77F orthologs results in lower male fertility and male-biased progeny. We show that defects in DNA compaction of X chromosome-bearing sperm relative to Y chromosome-bearing sperm during spermatogenesis result in fewer X-bearing mature sperm and more male-biased progeny. Unlike D. melanogaster, Mst77F is not essential for male fertility in D. yakuba but is still required to suppress sex-ratio distortion. Thus, sex-ratio distortion drives protamine rapid evolution in Drosophila species and may provide a universal explanation for the rapid evolution of protamines in animal species.
This work is supported by a Damon-Runyon Cancer Research Foundation postdoctoral fellowship DRG 2438-21 (to C-HC) and National Institutes of Health grant R01-GM74108 (to HSM). HSM is an Investigator of the Howard Hughes Medical Institute.