title: Mobile genes in the human microbiome are structured from global to individual scales.
abstract: Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA.|Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: I L
authors.initials: IL
authors.lastname: Brito
authors.affiliation: Sandia National Laboratories, Livermore, CA.
authors.forename: S
authors.initials: S
authors.lastname: Yilmaz
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Wildlife Conservation Society, Suva, Fiji.
authors.forename: S D
authors.initials: SD
authors.lastname: Jupiter
authors.affiliation: Edith Cowan University, Western Australia.
authors.forename: A P
authors.initials: AP
authors.lastname: Jenkins
authors.affiliation: Wildlife Conservation Society, Suva, Fiji.
authors.forename: W
authors.initials: W
authors.lastname: Naisilisili
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Tamminen
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: C S
authors.initials: CS
authors.lastname: Smillie
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: J R
authors.initials: JR
authors.lastname: Wortman
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: B W
authors.initials: BW
authors.lastname: Birren
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.|Massachusetts General Hospital, Boston, MA.|Center for Microbiome, Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: P C
authors.initials: PC
authors.lastname: Blainey
authors.affiliation: Sandia National Laboratories, Livermore, CA.
authors.forename: A K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA.
authors.forename: D
authors.initials: D
authors.lastname: Gevers
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA.|Broad Institute of MIT and Harvard, Cambridge, MA.|Center for Microbiome, Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Alm
mesh_terms: D001435:Bacteriophages / Q000235:genetics; D015331:Cohort Studies; D004251:DNA Transposable Elements / Q000235:genetics; D004032:Diet; D005367:Fiji; D005788:Gene Pool; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D059647:Gene-Environment Interaction; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D056186:Metagenomics; D064307:Microbiota / Q000235:genetics*; D009656:North America; D010957:Plasmids / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics*; D059010:Single-Cell Analysis
chemical_list: D004251:DNA Transposable Elements