Dynamics of genetic variation in transcription factors and its implications for the evolution of regulatory networks in Bacteria.

Aswin Sai Narain Seshasayee,Farhan Ali

doi:10.1093/nar/gkaa162

Abstract

The evolution of regulatory networks in Bacteria has largely been explained at macroevolutionary scales through lateral gene transfer and gene duplication. Transcription factors (TF) have been found to be less conserved across species than their target genes (TG). This would be expected if TFs accumulate mutations faster than TGs. This hypothesis is supported by several lab evolution studies which found TFs, especially global regulators, to be frequently mutated. Despite these studies, the contribution of point mutations in TFs to the evolution of regulatory network is poorly understood. We tested if TFs show greater genetic variation than their TGs using whole-genome sequencing data from a large collection of Escherichia coli isolates. TFs were less diverse than their TGs across natural isolates, with TFs of large regulons being more conserved. In contrast, TFs showed higher mutation frequency in adaptive laboratory evolution experiments. However, over long-term laboratory evolution spanning 60 000 generations, mutation frequency in TFs gradually declined after a rapid initial burst. Extrapolating the dynamics of genetic variation from long-term laboratory evolution to natural populations, we propose that point mutations, conferring large-scale gene expression changes, may drive the early stages of adaptation but gene regulation is subjected to stronger purifying selection post adaptation.

Highlights

The dynamic environments colonized by bacteria demand optimal regulation of gene expression [1]
Under the assumption that Transcription factors (TF) do not differ from their target genes (TG) in their underlying mutation rate and synonymous changes are under relatively weaker selection, TFs should be similar to TGs in their synonymous variation
When we performed paired comparisons, where a TF was only compared with its own TGs, we found all of the above estimates of diversity to be lower for TFs

Summary

Introduction

The dynamic environments colonized by bacteria demand optimal regulation of gene expression [1]. TRNs have been found to evolve faster than other biological networks [3], based on detection of orthologs across species. Their evolution has been explained largely by duplication [4] and horizontal gene transfer (HGT) [5]. Even though both of these processes are accompanied/followed by DNA sequence level changes in the TFs [6,7], the contribution of point mutations to TRN evolution is poorly understood [8]. The significance of point mutations can be realized by the fact that, even where both a TF and its TG are present, the regulatory interaction is often not conserved [9]

Methods

Results

Conclusion