Combined Analysis of Variation in Core, Accessory and Regulatory Genome Regions Provides a Super-Resolution View into the Evolution of Bacterial Populations.

Alan Mcnally ,Steven Dunn ,James O Mcinerney ,Yaara Oren ,Amgad Ashour ,Zhiyong Zong ,Michael B Prentice ,Lothar H Wieler ,Samuel K Sheppard ,Oren Avram ,Darren J Kelly ,Tristan Sreecharan ,Tal Pupko ,Sebastian Guenther ,Ivan Literák ,Ulrich Dobrindt ,Ben Pascoe ,Minna Vehkala ,Katharina Schaufler ,Niko Välimäki ,Jukka Corander

doi:10.1371/journal.pgen.1006280

Abstract

The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug–resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.

Highlights

The ability to sequence hundreds or thousands of bacteria genomes in a timely and cost effective manner has allowed microbiologists to study microbial evolution at an unprecedented scale and level of resolution [1]
We present an approach to evolutionary analysis of bacterial pathogens combining core genome, accessory genome, and gene regulatory region analyses
This enables unparalleled resolution of the evolution of a multi-drug resistant pandemic pathogen that would remain invisible to a core genome phylogenetic analysis alone

Summary

Introduction

The ability to sequence hundreds or thousands of bacteria genomes in a timely and cost effective manner has allowed microbiologists to study microbial evolution at an unprecedented scale and level of resolution [1]. Core genomes can be obtained by mapping genome data against a common reference sequence or by extracting the coding sequences (CDS) which are common across all members of a given data set. This approach has led to significant discoveries of the emergence of pathogenic bacteria [2,3,4,5], and allows fine scale analysis to inform interpretation of transmission events [6,7]. Integrating accessory gene pool analysis can improve the resolution of core genome phylogenetic studies. A study of the accessory genome of Klebsiella pneumoniae identified virulence loci significantly associated with isolates from invasive disease [11]

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Discussion

Conclusion