Replacement and Parallel Simplification of Nonhomologous Proteinases Maintain Venom Phenotypes in Rear-Fanged Snakes

Author(s):Show less -

Bayona-Serrano, Juan David ^[1] ; Viala, Vincent Louis ^{[1, 2]} ; Rautsaw, Rhett M. ^[3] ; Schramer, Tristan D. ^[3] ; Barros-Carvalho, Gesiele A. ^[1] ; Nishiyama, Jr., Milton Yutaka ^{[1, 2]} ; Freitas-de-Sousa, Luciana A. ^[4] ; Moura-da-Silva, Ana Maria ^{[4, 5]} ; Parkinson, Christopher L. ^{[3, 6]} ; Grazziotin, Felipe Gobbi ^[7] ; Junqueira-de-Azevedo, Inacio L. M. ^{[1, 2]}

Affiliation

^[1] Inst Butantan, Lab Especial Toxinol Aplicada, Sao Paulo - Brazil

^[2] Ctr Toxins Immune Response & Cell Signaling CeTIC, Sao Paulo - Brazil

^[3] Clemson Univ, Dept Biol Sci, Clemson, SC 29634 - USA

^[4] Inst Butantan, Lab Imunopatol, Sao Paulo - Brazil

^[5] Inst Pesquisa Clin Carlos Borborema, Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas - Brazil

^[6] Clemson Univ, Dept Forestry & Environm Conservat, Clemson, SC - USA

^[7] Inst Butantan, Lab Colecoes Zool, Sao Paulo - Brazil

• Document type: Journal article
• Source: Molecular Biology and Evolution; v. 37, n. 12, p. 3563-3575, DEC 2020.
• Web of Science Citations: 1

Abstract

Novel phenotypes are commonly associated with gene duplications and neofunctionalization, less documented are the cases of phenotypic maintenance through the recruitment of novel genes. Proteolysis is the primary toxic character of many snake venoms, and ADAM metalloproteinases, named snake venom metalloproteinases (SVMPs), are largely recognized as the major effectors of this phenotype. However, by investigating original transcriptomes from 58 species of advanced snakes (Caenophidia) across their phylogeny, we discovered that a different enzyme, matrix metalloproteinase (MMP), is actually the dominant venom component in three tribes (Tachymenini, Xenodontini, and Conophiini) of rear-fanged snakes (Dipsadidae). Proteomic and functional analyses of these venoms further indicate that MMPs are likely playing an ``SVMP-like{''} function in the proteolytic phenotype. A detailed look into the venom-specific sequences revealed a new highly expressed MMP subtype, named snake venom MMP (svMMP), which originated independently on at least three occasions from an endogenous MMP-9. We further show that by losing ancillary noncatalytic domains present in its ancestors, svMMPs followed an evolutionary path toward a simplified structure during their expansion in the genomes, thus paralleling what has been proposed for the evolution of their Viperidae counterparts, the SVMPs. Moreover, we inferred an inverse relationship between the expression of svMMPs and SVMPs along the evolutionary history of Xenodontinae, pointing out that one type of enzyme may be substituting for the other, whereas the general (metallo)proteolytic phenotype is maintained. These results provide rare evidence on how relevant phenotypic traits can be optimized via natural selection on nonhomologous genes, yielding alternate biochemical components. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/50127-5 - Dimensions US-BIOTA São Paulo: scales of biodiversity: integrated studies of snake venom evolution and function across multiple levels of diversity
• Grantee: Inácio de Loiola Meirelles Junqueira de Azevedo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 17/24546-3 - Scales of biodiversity: integrated studies of snake evolution and venom function
• Grantee: Luciana Aparecida Freitas de Sousa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/24498-9 - Venomics analyses of Dipsadinae snakes focusing on adaptations to ophiophagy
• Grantee: Juan David Bayona Serrano
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)