Microbial strain-level population structure and genetic diversity from metagenomes.
Among the human health conditions linked to microbial communities, phenotypes are often associated with only a subset of strains within causal microbial groups. Although it has been critical for decades in microbial physiology to characterize individual strains, this has been challenging when using culture-independent high-throughput metagenomics. We introduce StrainPhlAn, a novel metagenomic strain identification approach, and apply it to characterize the genetic structure of thousands of strains from more than 125 species in more than 1500 gut metagenomes drawn from populations spanning North and South American, European, Asian, and African countries. The method relies on per-sample dominant sequence variant reconstruction within species-specific marker genes. It identified primarily subject-specific strain variants (<5% inter-subject strain sharing), and we determined that a single strain typically dominated each species and was retained over time (for >70% of species). Microbial population structure was correlated in several distinct ways with the geographic structure of the host population. In some cases, discrete subspecies (e.g., forEubacterium rectaleandPrevotella copri) or continuous microbial genetic variations (e.g., forFaecalibacterium prausnitzii) were associated with geographically distinct human populations, whereas few strains occurred in multiple unrelated cohorts. We further estimated the genetic variability of gut microbes, withBacteroidesspecies appearing remarkably consistent (0.45% median number of nucleotide variants between strains), whereasP. copriwas among the most plastic gut colonizers. We thus characterize here the population genetics of previously inaccessible intestinal microbes, providing a comprehensive strain-level genetic overview of the gut microbial diversity.
Centre for Integrative Biology, University of Trento, 38123 Trento, Italy.
Duy Tin
0000-0002-4169-7727
DT
Truong
Centre for Integrative Biology, University of Trento, 38123 Trento, Italy.
Adrian
A
Tett
Centre for Integrative Biology, University of Trento, 38123 Trento, Italy.
Edoardo
0000-0003-0799-3490
E
Pasolli
Biostatistics Department, Harvard School of Public Health, Boston, Massachusetts 02115, USA.|The Broad Institute, Cambridge, Massachusetts 02142, USA.
Curtis
0000-0002-1110-0096
C
Huttenhower
Centre for Integrative Biology, University of Trento, 38123 Trento, Italy.
Nicola
0000-0002-1583-5794
N
Segata
D000465:Algorithms; D001439:Bacteroides / Q000235:genetics / Q000302:isolation & purification; D005051:Eubacterium / Q000235:genetics / Q000302:isolation & purification; D015894:Genome, Human; D006801:Humans; D054892:Metagenome; D064307:Microbiota; D058889:Molecular Typing / Q000379:methods; D011110:Polymorphism, Genetic; D018720:Prevotella / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA / Q000379:methods