Pervasive relaxed selection on spermatogenesis genes coincident with the evolution of polygyny in gorillas

Abstract

Gorillas have a polygynous social system in which the highest-ranking male has almost exclusive access to females and sires most of the offspring in the troop. Such behavior results in a dramatic reduction of sperm competition, which is ultimately associated with numerous traits that cause low efficacy of gorilla spermatogenesis. However, the molecular basis behind the remarkable erosion of the gorilla male reproductive system remains unknown. Here, we explored the genetic consequences of the polygynous social system in gorillas by testing for altered selection intensity across 13,310 orthologous protein-coding genes from 261 Eutherian mammals. We identified 578 genes with relaxed purifying selection in the gorilla lineage, compared with only 96 that were positively selected. Genes under relaxed purifying selection in gorillas have accumulated numerous deleterious amino acid substitutions, their expression is biased towards male germ cells, and are enriched in functions related to meiosis and sperm biology. We tested the function of gorilla relaxed genes previously not implicated in sperm biology using the Drosophila model system and identified 41 novel spermatogenesis genes required for normal fertility. Furthermore, by exploring exome/genome sequencing data of infertile men with severe spermatogenic impairment, we found that the human orthologs of the gorilla relaxed genes are enriched for loss-of-function variants in infertile men. These data provide compelling evidence that reduced sperm competition in gorillas is associated with relaxed purifying selection on genes related to male reproductive function. The accumulation of deleterious mutations in these genes likely provides the mechanistic basis behind the low efficacy of gorilla spermatogenesis and uncovers new candidate genes for human male infertility.

Rapid evolution of genes with anti-cancer functions during the origins of large bodies and cancer resistance in elephants

“…Therefore, we used two complementary methods, ABSREL (Smith et al, 2015) and BUSTED (Murrell et al, 2015a), to identify genes with evidence of positive selection in the elephant lineage. We used a dataset of alignments from 13,310 orthologous genes from 261 Eutherian mammals that we previously reported (Bowman et al, 2023b) and a phylogeny with Paenungulates collapsed to a polytomy to reflect that most genes lack significant phylogenetic support for the resolution of this clade ( Figure 1A ) (Bowman et al, 2023a). The ABSREL and BUSTED models are variants of the branch-sites random effect likelihood (BSREL) model of coding sequence evolution (Pond et al, 2011a; Smith et al, 2015), which allows for variation in d N / d S (ω) rates across lineages and sites; however, while ABSREL selects the optimal number of rate categories for each gene, BUSTED imposes three rate categories such that ω 1 ≤ω 2 ≤ω 3 ( Figure 1B ).…”

“…We previously reported the assembly of protein-coding gene alignments from the genomes of 261 Eutherian (“Placental”) mammals (Bowman et al, 2023b), which are also used in this study. Briefly, we used a reciprocal best BLAT hit (RBBH) approach to assemble a dataset of orthologous coding gene alignments from the genomes of 261 Eutherian (“Placental”) mammals ( Figure 1A ; Figure 1 – source data 1 ).…”

“…The multiple sequence alignments used in this study have been described elsewhere (Bowman et al, 2023b). Methods to infer the strength and direction of selection acting on molecular sequences, such as those to identify pervasive and episodic adaptive evolution (“positive selection”), are often based on estimating the ratio of non-synonymous ( d N ) to synonymous ( d S ) substitution rates ( d N / d S or ω ) in an alignment of homologous genes.…”

Positive selection analyses identify a single WWE domain residue that shapes ZAP into a super restriction factor

“…More complete details on the alignment and phylogenetic tree reconstruction are given in (56) as the same exact pipeline was used for this study.…”