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bioRxiv · 10.1101/2025.07.04.663182

Evolutionary dynamics of the vertebrate Wnt gene repertoire

Fogg, L. G.·Policarpo, M.·Salzburger, W.
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Abstract

The Wnt gene family plays a central role in vertebrate development, yet its evolutionary dynamics across lineages remain largely unexplored. Here, we present the most comprehensive analysis of Wnt gene evolution in vertebrates to date, leveraging a large-scale comparative genomics approach of 38,886 Wnt gene sequences mined from 1,961 species. We first investigate overall patterns of gene retention, duplication, and loss, and then focus specifically on the impact of whole-genome duplications (WGDs). We uncover striking variation in Wnt gene repertoire sizes, with ray-finned fishes (Actinopterygii) exhibiting the largest repertoires - even after excluding taxa with recent WGDs. Notably, we identify extreme expansions in polyploid cyprinids, including an octoploid hybrid harbouring 99 Wnt genes, the highest number observed. Unexpectedly elevated Wnt copy numbers in diploid species, such as the Antarctic lanternfish (Electrona antarctica) and the brook lamprey (Lethenteron reissneri), point to lineage-specific expansions with potential adaptive significance. Evolutionary rate analyses reveal that certain Wnt clades - especially Wnt8 and Wnt16 - exhibit elevated dN/dS ratios and high birth-death rates, indicative of repeated episodes of relaxed constraint or adaptive diversification. Contrary to our expectations, there was no relationship between developmental expression timing and evolutionary rates, suggesting pleiotropic regulation and functional redundancy of Wnt genes. Altogether, our findings reveal pervasive, lineage-specific remodelling of Wnt gene repertoires, shaped by both genome duplication history and divergent evolutionary trajectories. This work provides a high-resolution framework for understanding the molecular evolution of a key developmental toolkit and highlights candidate genes for future studies of vertebrate eco-morphological diversity.

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Fogg, L. G., Policarpo, M., Salzburger, W.. 2025-07-07. Evolutionary dynamics of the vertebrate Wnt gene repertoire. https://doi.org/10.1101/2025.07.04.663182

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