Covering all the bases with next-generation sequencing

Covering all the bases with next-generation sequencing In this article in Microbiology Today Ed Feil describes how we must brace ourselves for the next wave of data as new sequencing techniques become available to determine and compare many sequences at once. The enormous amount of data soon to be generated will bring exciting new insights into how micro-organisms within communities evolve and interact:

Regardless of the species in question, announcements of completed genome sequencing projects in the mainstream media almost invariably make reference to ‘cracking a code’ or ‘deciphering a genetic blueprint’. For bacteria, these over-used analogies spectacularly fail to give a true sense of the fluidity of genome evolution. The doe-eyed assumption in the mid-1990s that a single genome sequence can safely be considered as a prescriptive ‘solution’ for a given bacterial species has been dramatically falsified. By the late 1990s, multiple genome sequences for Escherichia coli revealed extensive differences in gene content between strains, and it rapidly became clear that, for many taxa, an individual genome is most usefully considered as one of many possible combinations of genes drawn from a vast pool known as the pangenome. When faced with such a maelstrom, our natural inclination (as good cladists) is to try and tidy it up, and catalogue strains into pockets of relatedness. Fortunately, phylogenetic analyses are possible, even for very variable species like E. coli, because one can readily identify genes which are universally present in all strains. These essential ‘core’ genes can be thought of as representing the operating system of a given species. In contrast, the specialist software is provided by ‘non-core’ or ‘accessory’ genes which are variably present or absent, are commonly acquired by horizontal transfer, and tend to be restricted to hypervariable regions called genomic islands. These two sets of genes present a fundamental duality in bacterial genomics. Whilst core genes can satisfy our requirements for molecular phylogeny (i.e. what a strain is), accessory genes often play a significant role in adaptation and phenotypic differences (i.e. what a strain does). Conflicts between these two can go a long way to explaining the mystery behind the muddle that is bacterial systematics.

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