Decay of Skin-Specific Gene Modules in Pangolins

Abstract

The mammalian skin exhibits a rich spectrum of evolutionary adaptations. The pilosebaceous unit, composed of the hair shaft, follicle, and the sebaceous gland, is the most striking synapomorphy. The evolutionary diversification of mammals across different ecological niches was paralleled by the appearance of an ample variety of skin modifications. Pangolins, order Pholidota, exhibit keratin-derived scales, one of the most iconic skin appendages. This formidable armor is intended to serve as a deterrent against predators. Surprisingly, while pangolins have hair on their abdomens, the occurrence of sebaceous and sweat glands is contentious. Here, we explore various molecular modules of skin physiology in four pangolin genomes, including that of sebum production. We show that genes driving wax monoester formation, Awat1/2, show patterns of inactivation in the stem pangolin branch, while the triacylglycerol synthesis gene Dgat2l6 seems independently eroded in the African and Asian clades. In contrast, Elovl3 implicated in the formation of specific neutral lipids required for skin barrier function is intact and expressed in the pangolin skin. An extended comparative analysis shows that genes involved in skin pathogen defense and structural integrity of keratinocyte layers also show inactivating mutations: associated with both ancestral and independent pseudogenization events. Finally, we deduce that the suggested absence of sweat glands is not paralleled by the inactivation of the ATP-binding cassette transporter Abcc11, as previously described in Cetacea. Our findings reveal the sophisticated and complex history of gene retention and loss as key mechanisms in the evolution of the highly modified mammalian skin phenotypes.

Evolution of ion channels in cetaceans: A natural experiment in the Tree of life

“…2). This result is consistent with other studies in which a reduction in gene copy number in cetaceans and other groups is associated with evolutionary innovations (Feng et al 2014; Nery et al 2014; Sun et al 2017; Huelsmann et al 2019; Helsen et al 2020a; McGowen et al 2020; Cabrera et al 2021; Randall et al 2022; Zheng et al 2022; Osipova et al 2023; Pinto et al 2023). We annotated, on average, 192.56 ion channels in the genomes of the species included in our taxonomic sampling, representing 0.96% of the protein-coding genes (Fig.…”

“…Taking advantage of the advancement of genomic tools, these adaptations have been investigated from the molecular perspective to expand further our knowledge about the evolutionary process behind the conquest of an aquatic lifestyle (McGowen et al 2011; McGowen et al 2012; Nery, González, et al 2013; Nery, Arroyo, et al 2013; Sun et al 2013; Nery et al 2014; McGowen et al 2020). Interestingly, several studies have reported the loss of genes as a strategy of phenotypic evolution (Feng et al 2014; Nery et al 2014; Sun et al 2017; Huelsmann et al 2019; Helsen et al 2020a; McGowen et al 2020; Randall et al 2022; Zheng et al 2022; Osipova et al 2023; Pinto et al 2023).…”

Evolution and conservation genetics of pangolins

“…2020a,b; Haley 2022; Pinto et al. 2023). Hence, it has been speculated that the scales of pangolins serve as a compensatory mechanism for immune deficiency.…”

“…Li et al (2020) speculated that the evolution of scales may have helped pangolins better adapt to their living environment, which includes a fair amount of burrowing. Nevertheless, comparative genome analyses have revealed numerous pseudogenization events for skin-related genes, which have caused dysfunction of the sebaceous gland and skin pathogen defense system (Pinto et al 2023). Thus, further research is required to definitively clarify the driving forces behind the evolution of pangolin scales.…”

“…Nevertheless, comparative genome analyses have revealed numerous pseudogenization events for skin‐related genes, which have caused dysfunction of the sebaceous gland and skin pathogen defense system (Pinto et al. 2023). Thus, further research is required to definitively clarify the driving forces behind the evolution of pangolin scales.…”