Uncovering the Single Amino-Acid Polymorphisms of the Human Gut Ecosystem

Single
nucleotide polymorphisms (SNPs) are the most common type
of genetic variation in the gut microbial metagenome and the host
genome, but they could not adequately represent the protein-level
variants. Single amino-acid polymorphisms (SAP) derived from nonsynonymous
SNPs can cause functional changes of proteins and are important forces
of adaption. However, SAP remains quite unexplored for the human gut
microbiome. Here, we present a comprehensive large-scale analysis
of SAP in the gut ecosystem, introducing a rigorous computational
pipeline for detecting such protein variation from 992 published human
metaproteomes. We find varied yet elaborate SAP patterns, capturing
both known and novel functions and adaptive strategies of gut microbes.
Microbial SAP is enriched in the outermost shell, motility devices,
and ribosomes. Generally, gut microbial SAP is more convergent in
metabolic subpathway regions and is enriched in the initial steps
of carbohydrate metabolism pathways that catalyze the formation and
isomerization of phosphorylated sugars. Furthermore, microbial and
host mutant peptide patterns were altered and exhibited significant
correlations in both inflammatory bowel disease and type 1 diabetes.
Our results highlight the functional and clinically relevant implications
and potential host–microbial interactions of gut ecosystem
SAP.