Open AccessA most wanted list of conserved microbial protein families with no known domains
Author(s) -
Stacia K. Wyman,
Aram Avila-Herrera,
Stephen Nayfach,
Katherine S. Pollard
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205749
Subject(s) - human microbiome project , metagenomics , biology , phylogenetic tree , computational biology , annotation , protein domain , protein function , function (biology) , gene , conserved sequence , protein family , novelty , phylogenetics , protein sequencing , evolutionary biology , genetics , peptide sequence , philosophy , theology
The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a “most wanted” list of genes to prioritize for further characterization.