Comparative pangenome and mobilome analysis of clostridial species clusters reveals different levels of host adaptation and novel conserved biosynthetic potential

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Abstract

Background

The class Clostridia comprises a diverse and industrially relevant group of anaerobes, ranging from free-living soil inhabitants to beneficial human gut symbionts. Analysing their genomic history and ecological adaptation dynamics beyond the species level allows us to gain deeper insights into their evolutionary traits and understand the impact of host adaptation on their innate functional capabilities.

Results

We constructed pangenomes and built core genome phylogenies for four ecologically distinct clostridial species clusters (rRNA clusters I, IV, XIVa and XIVb), analysing 492 clostridial genomes in total. All pangenomes were functionally annotated and fitted into a genomic divergence rate model, revealing a striking contrast in metabolic versatility and evolutionary dynamics among the host-associated clusters, IV and XIVa. Based on these findings, we hypothesized that cluster XIVa species are in the earlier stages of a host adaptation process compared to their cluster IV relatives. Targeted follow-up analyses confirmed this and yielded two additional key findings. First, cluster XIVa species are comparably less dependent on their host metabolically, and possess a more extensive secondary metabolism than anticipated for a host-associated clade. Second, a remarkable conservation of ranthipeptide biosynthetic gene clusters reveals underexplored biosynthetic potential with significant evolutionary advantages.

Conclusions

These results show that comparing genomic patterns beyond the species level can uncover distinct ecological trends, such as host and niche adaptation, across entire species groups. Understanding these trends provides valuable insights into the metabolic versatility and biosynthetic potential of these groups.

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