Molecular Evolution across Mouse Spermatogenesis

Abstract

Genes involved in spermatogenesis tend to evolve rapidly, but we lack a clear understanding of how protein sequences and patterns of gene expression evolve across this complex developmental process. We used fluorescence activated cell sorting (FACS) to generate expression data for early (meiotic) and late (postmeiotic) cell types across thirteen inbred strains of mice (Mus) spanning ∼7 million years of evolution. We used these comparative developmental data to investigate the evolution of lineage-specific expression, protein-coding sequences, and expression levels. We found increased lineage-specificity and more rapid protein-coding and expression divergence during late spermatogenesis, suggesting that signatures of rapid testis molecular evolution are punctuated across sperm development. Despite strong overall developmental parallels in these components of molecular evolution, protein and expression divergences were only weakly correlated across genes. We detected more rapid protein evolution on the X chromosome relative to the autosomes, while X-linked gene expression tended to be relatively more conserved likely reflecting chromosome-specific regulatory constraints. Using allele-specific FACS expression data from crosses between four strains, we found that the relative contributions of different regulatory mechanisms also differed between cell types. Genes showing cis-regulatory changes were more common late in spermatogenesis, and tended to be associated with larger differences in expression levels and greater expression divergence between species. In contrast, genes with trans-acting changes were more common early and tended to be more conserved across species. Our findings advance understanding of gene evolution across spermatogenesis and underscore the fundamental importance of developmental context in molecular evolutionary studies.

The genomic basis of hybrid male sterility in Ficedula flycatchers

“…Our results may appear contractionary in the light of the first developmental stages of spermatogenesis (i.e. mitosis and meiosis) being known to be strongly evolutionary constrained both in mammals (Larson et al, 2018;Kopania et al, 2022) and in birds (Segami et al 2022). Most of the known examples of genes associated with hybrid sterility in animals are, in fact, expressed during either the pre-or post-meiotic stages of gametogenesis (Coyne & Orr, 2004).…”

Speciation and development

“…Mathematical and simulated gene regulatory networks to investigate reproductive isolation Nosil et al (2017); Schiffman and Ralph (2021); ; Tulchinsky, Johnson, Watt, and Porter (2014) Allele-specific expression inference of cis-and trans-regulatory divergence in hybrid misexpression Coolon et al (2014); Kerwin and Sweigart (2020); Kopania et al (2022); Mack and Nachman (2017); McGirr and Martin (2020); Sánchez-Ramírez et al (2021) Evaluating molecular evolution, hybrid misexpression, and reproductive isolation over the timecourse of ontogeny Bundus et al (2015); Cutter and Bundus (2020); Diz et al (2022); Liu and Robinson-Rechavi (2018a); Liu et al (2021); Malone and Fontenot (2008); Turissini et al (2017) Developmental genetic characterization of key traits in reproductive isolation Cohen et al (2021); Indjeian et al (2016); Jiggins et al (2017); Mallarino et al (2011); Reid et al (2021); Van Belleghem et al (2021) Characterization of hybrid incompatibility genes that influence development Arévalo et al (2021); Brekke and Good (2014); Chang et al (2021); Powell et al (2020); Sandkam et al (2020); Schartl (2008) a Examples of recent references are not exhaustive and include some review articles.…”

“…Despite the logic of divergence accruing more readily for CREs, transcriptomic gene expression evidence is mixed across studies in whether cis ‐regulatory divergence or trans ‐regulatory divergence controlling gene expression is more common (Figure 3) (Gordon & Ruvinsky, 2012; Kopania et al, 2022; Lemos et al, 2008; Mack et al, 2016; McGirr & Martin, 2020; McManus et al, 2010; Sánchez‐Ramírez et al, 2021; Tirosh et al, 2009; Verta & Jones, 2019; Wittkopp et al, 2008). In some cases, which mode is more prevalent can depend on which sex or tissue is examined (Kopania et al, 2022; Sánchez‐Ramírez et al, 2021; Wang et al, 2019). Those tissues that tend to show a greater incidence of trans ‐regulatory divergence may be more likely to contribute to hybrid incompatibility (Kopania et al, 2022).…”

“…In some cases, which mode is more prevalent can depend on which sex or tissue is examined (Kopania et al, 2022; Sánchez‐Ramírez et al, 2021; Wang et al, 2019). Those tissues that tend to show a greater incidence of trans ‐regulatory divergence may be more likely to contribute to hybrid incompatibility (Kopania et al, 2022). Moreover, tissue‐dependent differences in allelic dominance can contribute to single‐locus hybrid incompatibility (rather than multilocus DMIs), as appears to occur for Agouti Signaling Protein in wood warbler hybrids (de Zwaan et al, 2022).…”

Expression and Characterization of the Spats1 Gene and Its Response to E2/MT Treatment in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

“…Spermatogenesis is a complex process that involves a multiplicity of growth factors and cytokines [ 17 ]. Spats1 (spermatogenesis-associated serine-rich 1) is a gene that is tightly associated with spermatogenesis in mammals [ 18 ].…”