Microbial strain-level population structure and genetic diversity from metagenomes

Abstract

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 (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., for Eubacterium rectale and Prevotella copri) or continuous microbial genetic variations (e.g., for Faecalibacterium 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, with Bacteroides species appearing remarkably consistent (0.45% median number of nucleotide variants between strains), whereas P. copri was 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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Feb 06, 2017
Source ID
10.1101/gr.216242.116

Entities

People

  • Adrian Tett
  • Curtis Huttenhower
  • Duy Tin Truong
  • Edoardo Pasolli
  • Nicola Segata

Organizations

  • Army Research Office
  • Fondazione Caritro
  • LEO Pharma Research Foundation
  • Ministry of Education, Universities and Research
  • National Institutes of Health
  • National Science Foundation

Tags

Fields of Study

  • Biology
  • Environmental science

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Infectious Disease/Epidemiology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology