ERC Squamata - Networks

In this repository:
- ERC_analyses: contains coevolutionary networks and gene enrichments. See the associated readme.md file
- Figures_123.pdf: main figures (1, 2, 3)

Github repository: Squamata_Mitonuclear_Coevolution

Abstract
Mitonuclear coevolution plays a central role in coordinating the function of nuclear- and mitochondrial-encoded proteins. While this process is well documented for mitochondrial and nuclear oxidative phosphorylation (OXPHOS) genes, the extent to which mitonuclear coevolution extends beyond mitochondrial pathways remains poorly understood. Evolutionary Rate Covariation (ERC) provides a powerful framework to detect long-term coevolution by identifying pairs of proteins that exhibit covarying evolutionary rates across a shared phylogeny. Here, we applied ERC over 2.9 million protein pairs across the whole proteomes of 34 squamates and reconstructed coevolutionary networks. Functional enrichment on their first-neighbors confirmed that mitochondrial OXPHOS predominantly coevolve with energetic and metabolic pathways but also showed a strong and unexpected association with pigmentation-related processes.
To test whether coevolving proteins also share similar phylogenetic signals, we performed the Approximately Unbiased test across 2,334 alignments, recalling the deep mitonuclear discordance shown by Squamata. Although a subset of nuclear proteins supported the mitochondrial topology, these genes were generally poorly phylogenetically informative and not enriched for direct mitochondrial-related functions. Together, our results indicate that ERC robustly captures functional coevolutionary relationships extending beyond canonical mitonuclear interfaces, while phylogenetic topological mirroring among non-interacting proteins appears limited.