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A Segregating Structural Variant Defines Novel Venom Phenotypes in the Eastern Diamondback Rattlesnake

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Autor(es):
Nachtigall, Pedro G. ; Nystrom, Gunnar S. ; Broussard, Emilie M. ; Wray, Kenneth P. ; Junqueira-de-Azevedo, Inacio L. M. ; Parkinson, Christopher L. ; Margres, Mark J. ; Rokyta, Darin R.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: Molecular Biology and Evolution; v. 42, n. 4, p. 16-pg., 2025-04-01.
Resumo

Of all mutational mechanisms contributing to phenotypic variation, structural variants are both among the most capable of causing major effects as well as the most technically challenging to identify. Intraspecific variation in snake venoms is widely reported, and one of the most dramatic patterns described is the parallel evolution of streamlined neurotoxic rattlesnake venoms from hemorrhagic ancestors by means of deletion of snake venom metalloproteinase (SVMP) toxins and recruitment of neurotoxic dimeric phospholipase A2 (PLA2) toxins. While generating a haplotype-resolved, chromosome-level genome assembly for the eastern diamondback rattlesnake (Crotalus adamanteus), we discovered that our genome animal was heterozygous for a similar to 225 Kb deletion containing six SVMP genes, paralleling one of the two steps involved in the origin of neurotoxic rattlesnake venoms. Range-wide population-genomic analysis revealed that, although this deletion is rare overall, it is the dominant homozygous genotype near the northwestern periphery of the species' range, where this species is vulnerable to extirpation. Although major SVMP deletions have been described in at least five other rattlesnake species, C. adamanteus is unique in not additionally gaining neurotoxic PLA2s. Previous work established a superficially complementary north-south gradient in myotoxin (MYO) expression based on copy number variation with high expression in the north and low in the south, yet we found that the SVMP and MYO genotypes vary independently, giving rise to an array of diverse, novel venom phenotypes across the range. Structural variation, therefore, forms the basis for the major axes of geographic venom variation for C. adamanteus. (AU)

Processo FAPESP: 18/26520-4 - Caracterização da inter-relação entre transcriptomas, miRNomas e proteomas de glândulas de veneno de Bothrops fonsecai e Bothrops cotiara
Beneficiário:Pedro Gabriel Nachtigall
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
Beneficiário:Hugo Aguirre Armelin
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 16/50127-5 - Dimensions US-BIOTA São Paulo: scales of biodiversity: integrated studies of snake venom evolution and function across multiple levels of diversity
Beneficiário:Inácio de Loiola Meirelles Junqueira de Azevedo
Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
Processo FAPESP: 22/04988-0 - Caracterização e comparação de regiões promotoras e acentuadoras de genes de toxinas entre duas populações de Agkistrodon piscivorus usando os métodos de sequenciamento RNA-seq, ATAC-seq e CUT&RUN
Beneficiário:Pedro Gabriel Nachtigall
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado