Dynamics of genetic variation in Transcription Factors and its implications for the evolution of regulatory networks in Bacteria

Abstract

The evolution of bacterial regulatory networks 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 E coli isolates. We found TFs to be less diverse, across natural isolates, due to their regulatory roles. TFs were enriched in mutations in multiple adaptive lab evolution studies but not in mutation accumulation. However, over long-term evolution, relative frequency of mutations in TFs showed a gradual decay after a rapid initial burst. Our results suggest that point mutations, conferring large-scale expression changes, may drive the early stages of adaptation but gene regulation is subjected to stronger purifying selection post adaptation.

Rapid adaptation of a complex trait during experimental evolution ofMycobacterium tuberculosis

“…Similar findings have also been obtained in other systems, where experimentally evolved populations have shown adaptation in transcription factors and other global regulators, with global impacts on gene expression (Ali and Seshasayee, 2020; Conrad et al, 2010; Philippe et al, 2007; RodrÍguez-Verdugo et al, 2016; Saxer et al, 2014). These mutations occur quickly to enable rapid adaptation to new environments, and it is hypothesized that secondary selection may act to refine gene expression after the initial burst of adaptation (Ali and Seshasayee, 2020; RodrÍguez-Verdugo et al, 2016). Thorpe et al previously found evidence of positive selection at promoter sites in natural populations of M. tb , suggesting that adaptation in natural as well as experimental populations is facilitated by regulatory mutations (Thorpe et al, 2017).…”

“…This reflects general features of M. tb’s regulatory network, which exhibits a high degree of connectivity between regulatory pathways (Chauhan et al, 2016; Galagan et al, 2013) as well as a hierarchical structure in which master regulators can rapidly calibrate global patterns of gene expression (Chauhan et al, 2016; Parvati Sai Arun et al, 2018). Similar findings have also been obtained in other systems, where experimentally evolved populations have shown adaptation in transcription factors and other global regulators, with global impacts on gene expression (Ali and Seshasayee, 2020; Conrad et al, 2010; Philippe et al, 2007; RodrÍguez-Verdugo et al, 2016; Saxer et al, 2014). These mutations occur quickly to enable rapid adaptation to new environments, and it is hypothesized that secondary selection may act to refine gene expression after the initial burst of adaptation (Ali and Seshasayee, 2020; RodrÍguez-Verdugo et al, 2016).…”

The role of sigma factor competition in bacterial adaptation under prolonged starvation

“…Recently, it was shown that in the initial stages of evolution during LTSP, mutations in global regulators confer a higher fitness advantage -an effect that declines over time, leading to local regulators being mutated at a higher frequency later in the experiment [113]. Evidence for, and the role of GASP have also been detected in populations of vector-borne pathogens.…”

Adaptive strategies under prolonged starvation and role of slow growth in bacterial fitness

“…Recently, it was shown that in the initial stages of LTSP evolution, mutations in global regulators confer a higher fitness advantage-an effect that declines over time, leading to local regulators being mutated at a higher frequency later in the experiment (88). Evidence and role of GASP have been detected in pathogen populations as well-vector-borne pathogens like X. nematophila balance a trade-off between pathogenicity and the GASP phenotype, with the competitively advantageous lrp mutant subpopulations lacking transmissivity and virulence later in evolution (89).…”