Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Abstract

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find thatKLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.

A Comprehensive Multi-Omic Approach Reveals a Relatively Simple Venom in a Diet Generalist, the Northern Short-Tailed Shrew, Blarina brevicauda

“…The toxins associated with the KLK1 gene subfamily in eulipotyphlans follows a similar recruitment of venom genes via gene duplication. A recent study on another venomous eulipotyphlan, the Hispaniolan solenodon ( Solenodon paradoxus ), also KLK1-like proteins to be the main components of their venom ( Casewell et al. 2019 ).…”

“…If dietary breadth is a driver of venom complexity, then one would predict that venomous animals in the Order Eulipotyphla (shrews, moles, hedgehogs, and solenodons) would have extreme complexity of venom toxins. Predatory venom is found in only a few extant eulipotyphlan species ( Dufton 1992 ; Ligabue-Braun 2015 ; Rode-Margono and Nekaris 2015 ; Casewell 2019 ) and may be found in a few other species ( Nussbaum and Maser 1969 ; Folinsbee 2013 ; Camargo and Álvarez-Castañeda 2019) . The selective pressures leading to the evolution of venom in these shrew species is unclear because both venomous and nonvenomous species feed on a diversity of prey items from widely divergent animal groups, including Arthropoda, Annelida, Mollusca, and Chordata (Hamilton 1930; Hamilton 1941 ; Eadie 1952 ).…”

Collagen Sequence Analysis Reveals Evolutionary History of Extinct West Indies Nesophontes (Island-Shrews)

“…For example, N. micrus exhibits at least three substitutions from N. major and four from N. hemicingulus , whereas the latter has at least eight substitutions from N. paramicrus ( supplementary table S3 , Supplementary Material online). In contrast, there are five differences observed between the two extant solenodons that are considered by some as separate genera ( Casewell et al 2019 ). However, these differences derive from a substantially larger number of substitution sites, with 12 sites of variation in the COL1A1 chain and a further five sites in the COL1A2 chain.…”

The impact of bottlenecks and inbreeding on the genome of the endangered Pyrenean desman

“…In the first round, genes were predicted using two methods: directly from protein homology (option protein2genome=1) using exonerate (Slater and Birney 2005); and also with AUGUSTUS v3.3.2 (Stanke et al 2006), previously trained with a small fraction of the genome. For the protein homology prediction, we used the proteomes from the only four species of the Eulipotyphla order to which the Pyrenean desman belongs: Condylura cristata, Sorex araneus, and Erinaceus europaeus, all of them unpublished genomes from the Broad Institute available at GenBank (Clark et al 2016), and Solenodon paradoxus (Casewell et al 2019). In addition, we included the human proteome available at GenBank, as its completeness allowed us to detect additional genes.…”