Horizontal transfer of matrix metalloproteinase genes links early animal and microbial evolution

The early evolution of animals is characterized by the emergence of complex tissues, organs, and integument, made possible in part by the diversification of groups of structural proteins. The abundance of this new kind of organic material in the environment would have provided novel nutrient opportunities for microbes, as part of the beginnings of animal-microbial coevolution. Indeed, a diverse ensemble of extant microbial groups appear to possess the enzymatic ability to cleave collagen, the most abundant animal-specific protein, through the use of matrix metalloproteinases (MMPs). In animals, MMPs serve to reshape the extracellular matrix in the course of development, but their prevalence in the microbial world has been largely overlooked.

MMPs have extensive diversity in Bacteria, Eumetazoa, and Streptophyta. We show that in marine metagenomes, MMP abundance is highly correlated with chitinase abundance, implying that even microbial MMPs are associated with animal-derived substrates. Reconstructing the phylogeny of MMP proteins reveals a history of rapid diversification, as well as multiple interkingdom and interdomain horizontal gene transfers. Included among these is a transfer to the ancestral lineage of the archaeal family Methanosarcinaceae, constraining this group to postdate the evolution of collagen, and therefore animal diversification.

MMPs have an unusual genetic history, marked by multiple instances of gene transfer between bacteria and multicellular eukaryotes, a smoking gun for some of the earliest coevolution between prokaryotes and metazoans. By calculating an end-Permian divergence of Methanosarcina, we demonstrate that the phylogenies of substrate-specific enzymes can provide valuable older-bound age calibrations for improving molecular clock age estimates across the Tree of Life.