Researchers from the University of California, San Francisco (UCSF) and the Gladstone Institutes have developed a new tool for examining genetic differences within bacterial species and uncovering novel transmission patterns in mother-infant microbiomes and marine metagenomes. The researchers used the tool to generate data as part of a study that was published in Genome Research through an article entitled, “An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography.”
Within a given bacterial species, gene content can vary by 50% or more from the reference genome. “This suggests massive variability at the strain level that could have real functional consequences,” explained the article's senior study author, Katherine Pollard, Ph.D., professor at UCSF and the Gladstone Institutes. “We saw a need for a computationally efficient tool to quantify this variation from shotgun metagenomics data.”
Dr. Pollard and her colleagues developed the metagenomic intraspecies diversity analysis system (MIDAS) to rapidly profile differences in gene content and single nucleotide variants across bacterial strains. To build MIDAS, researchers initially generated a database of 31,007 high-quality bacterial genomes. Using a set of 30 “universal” genes, they hierarchically clustered the genomes to define species. The researchers were able to assign 8.6% of the previously unannotated genomes to a species and reassigned species for 9.8%.
Once the MIDAS system was functioning up to the investigators' standards, the team applied the system to 98 mother and infant stool metagenomes—using strain-level genetic differences to track bacteria between mothers and babies.
“Strain-level variants reveal patterns that contradict what one would assume from patterns at the species level,” noted Stephen Nayfach, the study's lead author and a graduate student in Dr. Pollard’s laboratory.
Previous studies suggested that mother and infant microbiomes become more similar over the first year of life. However, by examining marker alleles, or rare genetic differences, the researchers found that early colonizing strains are transferred from the mother, but that late colonizing strains are different and likely acquired from the environment.
“The maturation of the infant gut microbiome over the first year gives the impression of ongoing transmissions from the mother,” said Dr. Pollard. “But the genetic variants in the bacteria show that the acquired strains are often not the same as the mother's.”
Interestingly, the research team applied MIDAS to marine samples collected at varying depths across the world's oceans. They found that the most prevalent marine bacteria had differences in gene content that were strongly associated with geography. Additional work will be needed to distinguish whether genetic differences between locations are the result of adaptation or genetic drift within the species.
“The next big challenge is to disentangle the forces that drive population structure in the microbiome and to associate this variability with traits of the host or environment,” Dr. Pollard concluded.