Transcriptomic Insights Into the Evolution of Snake Venom: Mechanisms, Diversity, and Adaptation.

Abstract

Snake venoms are evolutionarily refined biochemical arsenals composed of diverse toxins with complex functional roles in predation, defense, and competition. Over the past 2 decades, transcriptomic approaches have transformed venom research by enabling high-resolution insights into gene expression dynamics, molecular diversity, and the evolutionary mechanisms driving venom variation across lineages. In this review, we present a comprehensive synthesis of snake venom transcriptomics literature and propose a conceptual framework structured around three major axes: (1) gene family expansion through duplication and neofunctionalization; (2) regulatory complexity encompassing transcriptional, posttranscriptional, and epigenetic modulation; and (3) ecological selection pressures shaping venom profiles in response to diet, habitat, and interspecific interactions. We integrate findings from diverse taxa and technologies, including bulk RNA sequencing, long-read transcriptomics, and spatial or single-cell approaches, to highlight progress and gaps in current knowledge. A bibliometric analysis of 358 studies from 2002 to 2024 reveals significant growth in the field, with key contributions from institutions in the United States, Brazil, and Australia. Despite this progress, transcriptomic research remains geographically and taxonomically biased, with challenges in toxin annotation, data standardization, and integrative multiomics still unresolved. We conclude by emphasizing the growing role of integration with other omics approaches, advancements in single-cell transcriptomics, and the emerging potential of computational modeling in reconstructing venom evolution.