TY - JOUR T1 - Cryptic functional variation in the human gut microbiome JF - bioRxiv DO - 10.1101/056614 SP - 056614 AU - Patrick H. Bradley AU - Katherine S. Pollard Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/06/02/056614.abstract N2 - Background The human gut microbiome harbors microbes thatperform diverse biochemical functions. Previous work suggested that functional variation between gut microbiota is small relative to taxonomic variation. However, these conclusions were largely based on broad pathways and qualitative patterns. Identifying microbial genes with highly variableor invariable abundance across hosts requires a new statistical test.Results We develop a model for microbiome gene abundance that allows for differences in means between studies and accounts for the mean-variance relationship in shotgun data. Applying a test based on this model to stool metagenomes from three populations of healthy adults, we discover many significantly variable genes, including components of central carbon metabolism and other pathways comprised primarily of more stable genes. By integrating taxonomic profiles into our test for gene variability,we reveal that Proteobacteria are a major source of variable genes. Stablegenes tend to have broad phylogenetic distributions, but several two-component signaling pathways and carbohydrate utilization gene families have relatively constant levels across hosts despite being taxonomicallv restricted.Conclusions Gene-level tests shed light on adaptation to the gut environment, and highlight microbiallv-encoded functions that may respond to or cause variability in host traits. ER -