Scientists at the University of Washington have developed a new approach to study microbes in the wild, which will allow researchers to sequence the genomes of individual species from highly complex mixtures. It marks a big advance for understanding the enormous diversity of microbial communities —including the human microbiome. This new method can cluster sequence fragments from a mixed sample of yeasts into species. In the shown graph, each of the 12 species with a substantial presence in the mix are represented by a cluster. Each fragment is shown as a dot, with size indicating length, colored by species. Line widths represent the densities of links between the fragment shown.
The work is described in an article published May 22 in Early Online form in the journal G3: Genes|Genomes|Genetics, published by the Genetics Society of America.
"This new method will allow us to discover many currently unknown microbial species that can't be grown in the lab, while simultaneously assembling their genome sequences," says co-author Maitreya Dunham, a biologist at the University of Washington's Department of Genome Sciences.
Microbial communities, whether sampled from the ocean floor or a human mouth, are made up of many different species living together. Standard methods for sequencing these communities combine the information from all the different types of microbes in the sample. The result is a hodgepodge of genes that is challenging to analyze, and unknown species in the sample are difficult to discover.
"Our approach tells us which sequence fragments in a mixed sample came from the same genome, allowing us to construct whole genome sequences for individual species in the mix," says co-author Jay Shendure, also of the University of Washington's Department of Genome Sciences.
The key advance was to combine standard approaches with a method that maps out which fragments of sequence were once near each other inside a cell. The cells in the sample are first treated with a chemical that links together DNA strands that are in close proximity. Only strands that are inside the same cell will be close enough to link. The DNA is then chopped into bits, and the linked portions are isolated and sequenced.
Species-Level Deconvolution of Metagenome Assemblies with Hi-C-Based Contact Probability Maps Joshua N. Burton, Ivan Liachko, Maitreya J. Dunham, and Jay Shendure. G3: Genes|Genomes|Genetics g3.114.011825; Early Online May 22, 2014, DOI: 10.1534/g3.114.011825 ; PMID 24855317