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

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.

Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis

“…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 TFs 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 ).…”

“…Similar findings have also been obtained in other systems, where experimentally evolved populations have shown adaptation in TFs 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, 2017 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.…”

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.…”