Proteome-wide evidence for enhanced positive Darwinian selection within intrinsically disordered regions in proteins

Johan Nilsson,Mats Grahn,Anthony Ph Wright

doi:10.1186/gb-2011-12-7-r65

Johan Nilsson, Mats Grahn + Show 1 more

Open Access

https://doi.org/10.1186/gb-2011-12-7-r65

Copy DOI

Journal: Genome Biology	Publication Date: Jan 1, 2011
Citations: 147	License type: cc-by

Affiliation: Södertörn University, Karolinska Institutet

Abstract

BackgroundUnderstanding the adaptive changes that alter the function of proteins during evolution is an important question for biology and medicine. The increasing number of completely sequenced genomes from closely related organisms, as well as individuals within species, facilitates systematic detection of recent selection events by means of comparative genomics.ResultsWe have used genome-wide strain-specific single nucleotide polymorphism data from 64 strains of budding yeast (Saccharomyces cerevisiae or Saccharomyces paradoxus) to determine whether adaptive positive selection is correlated with protein regions showing propensity for different classes of structure conformation. Data from phylogenetic and population genetic analysis of 3,746 gene alignments consistently shows a significantly higher degree of positive Darwinian selection in intrinsically disordered regions of proteins compared to regions of alpha helix, beta sheet or tertiary structure. Evidence of positive selection is significantly enriched in classes of proteins whose functions and molecular mechanisms can be coupled to adaptive processes and these classes tend to have a higher average content of intrinsically unstructured protein regions.ConclusionsWe suggest that intrinsically disordered protein regions may be important for the production and maintenance of genetic variation with adaptive potential and that they may thus be of central significance for the evolvability of the organism or cell in which they occur.

Highlights

Understanding the adaptive changes that alter the function of proteins during evolution is an important question for biology and medicine
The frequency of codon sites under positive selection is enhanced in protein regions with intrinsically disordered structure The Fixed Effects Likelihood (FEL) method was used to predict codon sites under selection in the coding regions of 3,746 S. cerevisiae protein coding genes, for which inter-species alignments could be reliably constructed and for which no recombination events were predicted in the 37 S. cerevisiae and 27 S. paradoxus genome sequences used (Figure 1)
To investigate whether the pattern of selection on individual codon sites is correlated with the structural context of the encoded amino acids, the frequency of positively and negatively selected sites in intrinsically disordered region (IDR) as well as structured regions (a-helices and b-strands) was compared

Summary

Introduction

Understanding the adaptive changes that alter the function of proteins during evolution is an important question for biology and medicine. Understanding the process of adaptation is of central importance for many biological questions, such as how species respond to climate changes, pathogens or other environmental perturbations, as well for the mechanisms underlying genetic diseases, such as cancer. There is a need for approaches that help to predict the subclass of SNPs that are more likely to be of adaptive significance. The relevance of this task is underscored by the International HapMap Project, which uses genetic variation as a tool to better understand the molecular basis of human disease as well as the mechanisms underlying pharmaceutical therapy [10]

Methods

Results

Discussion

Conclusion