Patterns of Positive Selection and Neutral Evolution in the Protein-Coding Genes of Tetraodon and Takifugu

Juan I Montoya-Burgos

doi:10.1371/journal.pone.0024800

Abstract

Recent genome-wide analyses have revealed patterns of positive selection acting on protein-coding genes in humans and mammals. To assess whether the conclusions drawn from these analyses are valid for other vertebrates and to identify mammalian specificities, I have investigated the selective pressure acting on protein-coding genes of the puffer fishes Tetraodon and Takifugu. My results indicate that the strength of purifying selection in puffer fishes is similar to previous reports for murids but stronger in hominids, which have a smaller population size. Gene ontology analyses show that more than half of the biological processes targeted by positive selection in mammals are also targeted in puffer fishes, highlighting general patterns for vertebrates. Biological processes enriched with positively selected genes that are shared between mammals and fishes include immune and defense responses, signal transduction, regulation of transcription and several of their descendent terms. Mammalian-specific processes displaying an excess of positively selected genes are related to sensory perception and neurological processes. The comparative analyses also revealed that, for both mammals and fishes, genes encoding extracellular proteins are preferentially targeted by positive selection, indicating that adaptive evolution occurs more often in the extra-cellular environment rather than inside the cell. Moreover, I present here the first genome-wide characterization of neutrally-evolving regions of protein-coding genes. This analysis revealed an unexpectedly high proportion of genes containing both positively selected motifs and neutrally-evolving regions, uncovering a strong link between neutral evolution and positive selection. I speculate that neutrally-evolving regions are a major source of novelties screened by natural selection.

Highlights

Protein evolution is the outcome of the interplay between mutational processes and selective forces acting at the molecular level and, analyzing the coding fraction of a genome is fundamental for understanding how natural selection influences the evolution of organisms
The 16,950 protein-coding orthologous genes that were alignable over more than 10% of their sequence between the Takifugu and the Tetraodon represent 86.5 % of Tetraodon proteincoding genes and 91.5% of Takifugu protein-coding genes
Strength of selection In the comparison between Takifugu and Tetraodon, the strength of selection acting on protein-coding genes is given by an overall Ka/Ks ratio of 0.107, based on full-length coding sequence (CDS)

Summary

Introduction

Protein evolution is the outcome of the interplay between mutational processes and selective forces acting at the molecular level and, analyzing the coding fraction of a genome is fundamental for understanding how natural selection influences the evolution of organisms. It is generally assumed that functional elements of the genome, either coding or non-coding, show conserved sequences among related species due to purifying selection (Dermitzakis et al, 2002) During evolution, such elements have presumably reached functional local optima via adaptive evolution and thereafter, most mutations that modified the function must have been discarded by purifying selection. Genes that have less central functions tend to evolve at higher rates and a fraction of them may have experienced recent positive selection. Supporting this principle, it has been suggested that the evolutionary rate of protein-coding genes depend on protein dispensability [3] or on protein connectivity [4,5,6]

Methods

Results

Conclusion