Snake population venomics and antivenomics of Bothropsatrox: Paedomorphism along its transamazonian dispersaland implications of geographic venom variability on snakebite management

ABSTRACT

We describe two geographically differentiated venomphenotypes across the wide distributionrange of Bothrops atrox, fromthe ColombianMagdalena Medio Valley through Puerto Ayacuchoand El Paují, in the Venezuelan States ofAmazonas and Orinoquia, respectively, and São Bentoin the Brazilian State of Maranhão. Colombian and Venezuelan venoms show an ontogenetictoxin profile phenotype whereas Brazilian venoms exhibit paedomorphic phenotypes.Venoms from each of the 16 localities sampled contain both population-specific toxins andproteins shared by neighboring B. atrox populations.Mapping themolecular similarity betweenconspecific populations onto a physical map of B. atrox range provides clues for tracingdispersal routes that account for the current biogeographic distribution of the species. Theproteomic pattern is consistent with a model of southeast and southwest dispersal andallopatric fragmentation northern of the Amazon Basin, and trans-Amazonian expansionthrough the Andean Corridor and across the Amazon river between Monte Alegre andSantarém. An antivenomic approach applied to assess the efficacy towards B. atrox venoms oftwo antivenomsraised in Costa Rica and Brazil using Bothrops venomsdifferent than B. atrox inthe immunization mixtures showed that both antivenoms immunodepleted very efficientlythe major toxins (PIII-SVMPs, serine proteinases, CRISP, LAO) of paedomorphic venoms fromPuerto Ayacucho (Venezuelan Amazonia) through São Bento, but had impaired reactivitytowards PLA2 and P-I SVMP molecules abundantly present in ontogenetic venoms. The degreeofimmunodepletion achieved suggests that each of these antivenomsmay be effective againstenvenomations by paedomorphic, and some ontogenetic, B. atrox venoms.