Genetic Signatures of Evolution of the Pluripotency Gene Regulating Network across Mammals

Abstract

Mammalian pluripotent stem cells (PSCs) have distinct molecular and biological characteristics among species, but to date we lack a comprehensive understanding of regulatory network evolution in mammals. Here, we carried out a comparative genetic analysis of 134 genes constituting the pluripotency gene regulatory network across 48 mammalian species covering all the major taxonomic groups. We report that mammalian genes in the pluripotency regulatory network show a remarkably high degree of evolutionary stasis, suggesting the conservation of fundamental biological process of mammalian PSCs across species. Nevertheless, despite the overall conservation of the regulatory network, we discovered rapid evolution of the downstream targets of the core regulatory elements and specific amino acid residues that have undergone positive selection. Our data indicate development of lineage-specific pluripotency regulating networks that may explain observed variations in some characteristics of mammalian PSCs. We further revealed that positively selected genes could be associated with species’ unique adaptive characteristics that were not dedicated to regulation of PSCs. These results provide important insight into the evolution of the pluripotency gene regulatory network underlying variations in characteristics of mammalian PSCs.

Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis

“…Zelda (Liang et al, 2008), CLAMP (Colonnetta et al, 2021; Duan et al, 2021) and GAF (Gaskill et al, 2021) in Drosophila, though they seem to share many functional aspects with vertebrate pluripotency factors, including pioneering roles in opening repressed embryonic chromatin and establishing activating histone modifications (Blythe and Wieschaus, 2016; Gaskill et al, 2021; Hug et al, 2017). This diversity of strategies implies that the gene network regulating pluripotency has been extensively modified over evolutionary time (Endo et al, 2020; Fernandez-Tresguerres et al, 2010), though it is unknown when and under what circumstances major modifications arose.…”

Cytology, function and dynamics of stem and progenitor cells in decapod crustaceans

“…For example, full genome sequences have been obtained in recent years for decapods as diverse as crayfish Procambarus virginalis (Gutekunst et al ., 2018), shrimp Penaeus vannamei (Zhang et al ., 2019), lobster Homarus americanus (Polinski et al ., 2021) and crabs Eriocheir sinensis and Portunus trituberculatus (Tang et al ., 2020a,b). These genetic resources can now be mined for genes known to be involved in stem cell proliferation and regulation in animal models (Singh, 2015; Endo, Kamei & Inoue‐Murayama, 2020).…”

Generation of iPSCs from endangered Grevy’s zebra and comparative transcriptomic analysis of mammalian PSCs

“…These findings may shed light on the species differences in the characteristics of mammalian PSCs and imply the evolution of the unique molecular mechanisms of species for regulating PSCs. The protein-coding sequences of pluripotency-regulating genes have been evolutionarily conserved across mammals 22 . The high variations in gene expression patterns found in this study may suggest that the characteristic variations in mammalian PSCs may be explained by the differences in gene expression.…”

“…The comparative genetic approach is a powerful tool for elucidating evolution 21 . While we previously described the evolutionary pattern in the pluripotency gene regulatory network from changes in protein-coding genes 22 , changes in gene expression may enable further insights into the phenotypic differences and similarities between species 23 . Comparative PSC gene expression analysis has previously highlighted the common regulation of signalling pathways between primates and mice 24 ; evolutionary patterns across broader taxonomic lineages are poorly explored.…”