AUTHOR=González Dámariz , Morales-Olavarria Mauricio , Vidal-Veuthey Boris , Cárdenas Juan P. 

TITLE=Insights into early evolutionary adaptations of the Akkermansia genus to the vertebrate gut

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1238580

DOI=10.3389/fmicb.2023.1238580

ISSN=1664-302X

ABSTRACT=<p><italic>Akkermansia</italic>, a relevant mucin degrader from the vertebrate gut microbiota, is a member of the deeply branched Verrucomicrobiota, as well as the only known member of this phylum to be described as inhabitants of the gut. Only a few <italic>Akkermansia</italic> species have been officially described so far, although there is genomic evidence addressing the existence of more species-level variants for this genus. This niche specialization makes <italic>Akkermansia</italic> an interesting model for studying the evolution of microorganisms to their adaptation to the gastrointestinal tract environment, including which kind of functions were gained when the <italic>Akkermansia</italic> genus originated or how the evolutionary pressure functions over those genes. In order to gain more insight into <italic>Akkermansia</italic> adaptations to the gastrointestinal tract niche, we performed a phylogenomic analysis of 367 high-quality <italic>Akkermansia</italic> isolates and metagenome-assembled genomes, in addition to other members of Verrucomicrobiota. This work was focused on three aspects: the definition of <italic>Akkermansia</italic> genomic species clusters and the calculation and functional characterization of the pangenome for the most represented species; the evolutionary relationship between <italic>Akkermansia</italic> and their closest relatives from Verrucomicrobiota, defining the gene families which were gained or lost during the emergence of the last <italic>Akkermansia</italic> common ancestor (<italic>LAkkCA</italic>) and; the evaluation of the evolutionary pressure metrics for each relevant gene family of main <italic>Akkermansia</italic> species. This analysis found 25 <italic>Akkermansia</italic> genomic species clusters distributed in two main clades, divergent from their non-<italic>Akkermansia</italic> relatives. Pangenome analyses suggest that <italic>Akkermansia</italic> species have open pangenomes, and the gene gain/loss model indicates that genes associated with mucin degradation (both glycoside hydrolases and peptidases), (micro)aerobic metabolism, surface interaction, and adhesion were part of <italic>LAkkCA</italic>. Specifically, mucin degradation is a very ancestral innovation involved in the origin of <italic>Akkermansia</italic>. Horizontal gene transfer detection suggests that <italic>Akkermansia</italic> could receive genes mostly from unknown sources or from other Gram-negative gut bacteria. Evolutionary metrics suggest that <italic>Akkemansia</italic> species evolved differently, and even some conserved genes suffered different evolutionary pressures among clades. These results suggest a complex evolutionary landscape of the genus and indicate that mucin degradation could be an essential feature in <italic>Akkermansia</italic> evolution as a symbiotic species.</p>