Molecular mechanisms underlying intraspecific variation in snake venom

Author(s):Show less -

Amazonas, Diana R. ^[1] ; Portes-Junior, Jose A. ^[1] ; Nishiyama-Jr, Milton Y. ; Nicolau, Carolina A. ^[2] ; Chalkidis, Hipocrates M. ^[3] ; Mourao, V, Rosa H. ; Grazziotin, Felipe G. ^[4] ; Rokyta, Darin R. ^[5] ; Lisle Gibbs, H. ^[6] ; Valente, Richard H. ^[2] ; Junqueira-de-Azevedo, Inacio L. M. ^[7] ; Moura-da-Silva, Ana M. ^[1]

Affiliation

^[1] Inst Butantan, Lab Imunopatol, Av Vital Brazil, BR-05503900 Sao Paulo, SP - Brazil

^[2] Inst Oswaldo Cruz, FIOCRUZ, Lab Toxinol, Av Brasil 4365, BR-21040900 Rio De Janeiro, RJ - Brazil

^[3] Univ Fed Oeste Para UFOPA, Lab Bioprospeccao & Biol Expt, Programa Posgrad Recursos Nat Amazonia, Rua Vera Paz S-N, BR-68035110 Santarem, PA - Brazil

^[4] Inst Butantan, Lab Especial Colecoes Zool, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[5] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 - USA

^[6] Ohio State Univ, Dept Evolut Ecol & Organismal Biol, Columbus, OH 43210 - USA

^[7] Nishiyama-Jr, Jr., Milton Y., Inst Butantan, Lab Especial Toxinol Aplicada, Av Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 181, p. 60-72, JUN 15 2018.
• Web of Science Citations: 18

Abstract

Elucidating the molecular mechanisms underlying snake venom variability provides important clues for understanding how the biological functions of this powerful toxic arsenal evolve. We analyzed in detail individual transcripts and venom protein isoforms produced by five specimens of a venomous snake (Bothrops atrox) from two nearby but genetically distinct populations from the Brazilian Amazon rainforest which show functional similarities in venom properties. Individual variation was observed among the venoms of these specimens, but the overall abundance of each general toxin family was conserved both in transcript and in venom protein levels. However, when expression of independent paralogues was analyzed, remarkable differences were observed within and among each toxin group, both between individuals and between populations. Transcripts for functionally essential venom proteins ({''}core function{''} proteins) were highly expressed in all specimens and showed similar transcription/translation rates. In contrast, other paralogues ({''}adaptive{''} proteins) showed lower expression levels and the toxins they coded for varied among different individuals. These results provide support for the inferences that (a) expression and translational differences play a greater role in defining adaptive variation in venom phenotypes than does sequence variation in protein coding genes and (b) convergent adaptive venom phenotypes can be generated through different molecular mechanisms. Significance: Analysis of individual transcripts and venom protein isoforms produced by specimens of a venomous snake (Bothrops atrox), from the Brazilian Amazon rainforest, revealed that transcriptional and translational mechanisms contribute to venom phenotypic variation. Our finding of evidence for high expression of toxin proteins with conserved function supports the hypothesis that the venom phenotype consists of two kinds of proteins: conserved ``core function{''} proteins that provide essential functional activities with broader relevance and less conserved ``adaptive{''} proteins that vary in expression and may permit customization of protein function. These observations allowed us to suggest that genetic mechanisms controlling venom variability are not restricted to selection of gene copies or mutations in structural genes but also to selection of the mechanisms controlling gene expression, contributing to the plasticity of this important phenotype for venomous snakes. (AU)

• 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 type: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 12/16277-9 - Variability in venom composition of Bothrops snakes and functional relevance of the presence of distinct metaloproteinases in venom composition
• Grantee: Ana Maria Moura da Silva
• Support type: Regular Research Grants
• FAPESP's process: 14/26058-8 - Inhibition of mammalian and snake venom metalloproteinases by the recombinant pro-domain of jararhagin and its relevant peptide fragments
• Grantee: Ana Maria Moura da Silva
• Support type: Regular Research Grants