ECMME: Comprehensive Atlas of Evolutionary Selection Pressures on Mammalian Extracellular Matrix Proteins
Researchers have published a comprehensive per-residue analysis of selection pressures on 272 human core extracellular matrix (ECM) proteins, drawing on orthologous sequences from up to 228 placental mammal species. The study found that ECM proteins are predominantly under strong purifying selection, reflecting their structural indispensability, but also show episodic positive selection—particularly in collagens. The findings are made publicly accessible through a new interactive web browser called ECMME, offering a resource for interpreting functional and evolutionary sites across the matrisome.
A new preprint on bioRxiv presents ECMME (ECM Molecular Evolution), an atlas of evolutionary selection pressures mapped across 272 human core matrisome proteins. The researchers developed an automated pipeline that integrates ortholog identification, codon-aware alignments, and site-specific selection analyses using the MEME and FUBAR methods from the HyPhy suite, applied to sequences from up to 228 placental mammal species. The dominant signal across the matrisome is strong purifying selection, consistent with the ECM's essential roles in structural support and cellular regulation in multicellular organisms. However, the study also identifies episodic positive selection at specific sites, with collagens showing significantly higher rates of such selection compared to glycoproteins and proteoglycans—a contrast that may reflect lineage-specific functional adaptations. Pervasive positive selection, acting consistently across many lineages, was found to be rarer. To make these findings broadly accessible, the team built the ECMME browser, a free, open-access web tool that visualizes selection metrics directly onto protein topology diagrams without requiring local installation. The resource is intended to help researchers interpret functional sites and design experiments informed by evolutionary constraints.
What's missing
As a preprint, this work has not yet undergone formal peer review, so findings should be interpreted with caution. The study is limited to placental mammals, leaving open questions about whether similar evolutionary dynamics apply to other vertebrates or invertebrates. The functional significance of sites under episodic positive selection remains largely uncharacterized, and the biological drivers of elevated positive selection in collagens versus other matrisome classes are not fully explained. The analysis is also constrained by the quality and completeness of available genomic sequences across the 228 species included.
What different sources said
- bioRxivCenter
ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics
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