RT Journal Article
SR Electronic
T1 The large majority of intergenic sites in bacteria are selectively constrained, even when known regulatory elements are excluded
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 069708
DO 10.1101/069708
A1 Harry A. Thorpe
A1 Sion Bayliss
A1 Laurence D. Hurst
A1 Edward J. Feil
YR 2016
UL http://biorxiv.org/content/early/2016/08/15/069708.abstract
AB There are currently no broad estimates of the overall strength and direction of selection operating on intergenic variation in bacteria. Here we address this using large whole genome sequence datasets representing six diverse bacterial species; Escherichia coli, Staphylococcus aureus, Salmonella enterica, Streptococcus pneumoniae, Klebsiella pneumoniae, and Mycobacterium tuberculosis. Excluding M. tuberculosis, we find that a high proportion (62%-79%; mean 70%) of intergenic sites are selectively constrained, relative to synonymous sites. Non-coding RNAs tend to be under stronger selective constraint than promoters, which in turn are typically more constrained than rho-independent terminators. Even when these regulatory elements are excluded, the mean proportion of constrained intergenic sites only falls to 69%; thus our current understanding of the functionality of intergenic regions (IGRs) in bacteria is severely limited. Consistent with a role for positive as well as negative selection on intergenic sites, we present evidence for strong positive selection in Mycobacterium tuberculosis promoters, underlining the key role of regulatory changes as an adaptive mechanism in this highly monomorphic pathogen.