title: Global analysis of saliva as a source of bacterial genes for insights into human population structure and migration studies.
abstract: BACKGROUND
  The genetic diversity of the human microbiome holds great potential for shedding light on the history of our ancestors. Helicobacter pylori is the most prominent example as its analysis allowed a fine-scale resolution of past migration patterns including some that could not be distinguished using human genetic markers. However studies of H. pylori require stomach biopsies, which severely limits the number of samples that can be analysed. By focussing on the house-keeping gene gdh (coding for the glucose-6-phosphate dehydrogenase), on the virulence gene gtf (coding for the glucosyltransferase) of mitis-streptococci and on the 16S-23S rRNA internal transcribed spacer (ITS) region of the Fusobacterium nucleatum/periodonticum-group we here tested the hypothesis that bacterial genes from human saliva have the potential for distinguishing human populations.
  
  
  RESULTS
  Analysis of 10 individuals from each of seven geographic regions, encompassing Africa, Asia and Europe, revealed that the genes gdh and ITS exhibited the highest number of polymorphic sites (59% and 79%, respectively) and most OTUs (defined at 99% identity) were unique to a given country. In contrast, the gene gtf had the lowest number of polymorphic sites (21%), and most OTUs were shared among countries. Most of the variation in the gdh and ITS genes was explained by the high clonal diversity within individuals (around 80%) followed by inter-individual variation of around 20%, leaving the geographic region as providing virtually no source of sequence variation. Conversely, for gtf the variation within individuals accounted for 32%, between individuals for 57% and among geographic regions for 11%. This geographic signature persisted upon extension of the analysis to four additional locations from the American continent. Pearson correlation analysis, pairwise Fst-cluster analysis as well as UniFrac analyses consistently supported a tree structure in which the European countries clustered tightly together and branched with American countries and South Africa, to the exclusion of Asian countries and the Congo.
  
  
  CONCLUSIONS
  This study shows that saliva harbours protein-coding bacterial genes that are geographically structured, and which could potentially be used for addressing previously unresolved human migration events.
authors.affiliation: Division of Oral Microbiology and Immunology, Department for Operative Dentistry, Periodontology and Preventive Dentistry, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52057, Aachen, Germany. khenne@ukaachen.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Henne
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103, Leipzig, Germany. jingli1978@gmail.com.|Current address: Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. jingli1978@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103, Leipzig, Germany. stonekg@eva.mpg.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Stoneking
authors.affiliation: Division of Oral Microbiology and Immunology, Department for Operative Dentistry, Periodontology and Preventive Dentistry, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52057, Aachen, Germany. olga.kessler@rwth-aachen.de.
authors.forename: Olga
authors.initials: O
authors.lastname: Kessler
authors.affiliation: Division of Oral Microbiology and Immunology, Department for Operative Dentistry, Periodontology and Preventive Dentistry, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52057, Aachen, Germany. hildegardschilling@gmx.de.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Schilling
authors.affiliation: Division of Oral Microbiology and Immunology, Department for Operative Dentistry, Periodontology and Preventive Dentistry, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52057, Aachen, Germany. anne.sonanini@rwth-aachen.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Sonanini
authors.affiliation: Division of Oral Microbiology and Immunology, Department for Operative Dentistry, Periodontology and Preventive Dentistry, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52057, Aachen, Germany. gconrads@ukaachen.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Conrads
authors.affiliation: Division of Virology, Institute of Medical Microbiology, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52057, Aachen, Germany. hhorz@ukaachen.de.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horz
mesh_terms: D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D004269:DNA, Bacterial / Q000032:analysis; D005798:Genes, Bacterial; D005819:Genetic Markers; D005843:Geography; D063426:Human Migration; D006801:Humans; D012463:Saliva / Q000382:microbiology*
chemical_list: D004269:DNA, Bacterial; D005819:Genetic Markers