Estimates of molecular convergence reveal genes with intermediate pleiotropy underlying adaptive variation across teleost fish

Abstract

Molecular convergence, where specific non-synonymous changes in protein-coding genes lead to identical amino acid substitutions across multiple lineages, provides strong evidence of adaptive evolution. Detecting this signal across diverse taxa can reveal broad evolutionary mechanisms that may not be apparent when studying individual lineages. In this study, we search for convergent substitutions in the most speciose group of vertebrates, teleost fishes. Using an unsupervised approach, we detected convergence in 89 protein-coding genes across 143 chromosomal-level genomes. To assess their functional implications, we integrate data on protein properties, gene expression across species and tissues, single-cell RNA sequencing of zebrafish embryonic development, and gene perturbation experiments in zebrafish. The convergent genes were associated with diverse processes including embryonic development, tissue morphogenesis, metabolism, and responses to hormones and heat stress. The convergent substitutions altered amino acid properties, with some occurring at functionally critical sites. Notably, only one-third of these genes were tissue-specific, while the majority were expressed across multiple tissues and cell types. Genetic perturbation data further showed that the convergent genes can affect multiple structures across diverse tissues. These results highlight the pleiotropic nature of the convergent genes. Using an evolutionary modeling approach, we show that adaptive variation tends to accumulate in genes with intermediate pleiotropy, enabling organisms to overcome selective pressures during ecological shifts. Although traditionally considered a source of constraint, we argue that adaptation via genes with intermediate pleiotropy might be particularly advantageous following periods of ecological shifts, and can potentially lead to the evolution of convergent phenotypes.