Tracking the recruitment and evolution of snake toxins using the evolutionary context provided by the Bothrops jararaca genome

Author(s)

Almeida, Diego Dantas ^[1] ; Viala, Vincent Louis ^[1] ; Nachtigall, Pedro Gabriel ^[1] ; Broe, Michael ^[2] ; Gibbs, H. Lisle ^[2] ; Serrano, Solange Maria de Toledo ^[1] ; Moura-da-Silva, Ana Maria ^{[3, 4]} ; Ho, Paulo Lee ^[5] ; Nishiyama-Jr, Milton Yutaka ; Junqueira-de-Azevedo, Inacio L. M. ^[6]

Affiliation

^[1] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling, Lab Toxinol Aplicada, BR-05503900 Sao Paulo - Brazil

^[2] Ohio State Univ, Dept Ecol Evolut & Organismal Biol, Columbus, OH 43210 - USA

^[3] Inst Butantan, Lab Imunopatol, BR-05503900 Sao Paulo - Brazil

^[4] Univ Estado Amazonas UEA, Programa Posgrad Med Trop, BR-69040000 Manaus, Amazonas - Brazil

^[5] Inst Butantan, Div BioInd, Serv Bacteriol, BR-05503900 Sao Paulo - Brazil

^[6] Nishiyama-Jr, Jr., Milton Yutaka, Inst Butantan, Ctr Toxins Immune Response & Cell Signaling, Lab Toxinol Aplicada, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 118, n. 20 MAY 18 2021.
• Web of Science Citations: 0

Abstract

Venom is a key adaptive innovation in snakes, and how nonvenom genes were co-opted to become part of the toxin arsenal is a significant evolutionary question. While this process has been investigated through the phylogenetic reconstruction of toxin sequences, evidence provided by the genomic context of toxin genes remains less explored. To investigate the process of toxin recruitment, we sequenced the genome of Bothrops jararaca, a clinically relevant pitviper. In addition to producing a road map with canonical structures of genes encoding 12 toxin families, we inferred most of the ancestral genes for their loci. We found evidence that 1) snake venom metalloproteinases (SVMPs) and phospholipases A2 (PLA2) have expanded in genomic proximity to their nonvenomous ancestors; 2) serine proteinases arose by co-opting a local gene that also gave rise to lizard gilatoxins and then expanded; 3) the bradykinin-potentiating peptides originated from a C-type natriuretic peptide gene backbone; and 4) VEGF-F was co-opted from a PGF-like gene and not from VEGFA. We evaluated two scenarios for the original recruitment of non toxin genes for snake venom: 1) in locus ancestral gene duplication and 2) in locus ancestral gene direct co-option. The first explains the origins of two important toxins (SVMP and PLA2), while the second explains the emergence of a greater number of venom components. Overall, our results support the idea of a locally assembled venom arsenal in which the most clinically relevant toxin families expanded through posterior gene duplications, regardless of whether they originated by duplication or gene co-option. (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 Opportunities: BIOTA-FAPESP Program - Thematic Grants
• 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: 15/03509-7 - Genomic sequencing of Brazilian snakes focused on the study of toxins
• Grantee: Vincent Louis Viala
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 12/00177-5 - Genome sequencing of the snake Bothrops jararaca aiming at characterizing the structure of toxin genes and their regulatory elements
• Grantee: Inácio de Loiola Meirelles Junqueira de Azevedo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/26520-4 - Characterization of the interrelationship between transcriptomes, miRNomes and proteomes from the venom glands of Bothrops fonsecai and Bothrops cotiara
• Grantee: Pedro Gabriel Nachtigall
• Support Opportunities: Scholarships in Brazil - Post-Doctorate