Title: A most wanted list of conserved microbial protein families with no known domains

Journal Article · · PLoS ONE
 [1];  [2];  [3]; ORCiD logo [4];
  1. Gladstone Inst., San Francisco, CA (United States); Univ. of California, Berkeley, CA (United States); DOE/OSTI
  2. Gladstone Inst., San Francisco, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Gladstone Inst., San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
  4. Gladstone Inst., San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States)

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.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1627871
Report Number(s):
LLNL-JRNL-760201
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 10 Vol. 13; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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