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Abstract
Small proteins are traditionally overlooked due to computational and experimental
difficulties in detecting them. To systematically identify small proteins, we carried
out a comparative genomics study on 1,773 human-associated metagenomes from four different
body sites. We describe >4,000 conserved protein families, the majority of which are
novel; ∼30% of these protein families are predicted to be secreted or transmembrane.
Over 90% of the small protein families have no known domain and almost half are not
represented in reference genomes. We identify putative housekeeping, mammalian-specific,
defense-related, and protein families that are likely to be horizontally transferred.
We provide evidence of transcription and translation for a subset of these families.
Our study suggests that small proteins are highly abundant and those of the human
microbiome, in particular, may perform diverse functions that have not been previously
reported.