Widespread Positive Selection For MRNA Secondary Structure At Synonymous Sites In Domesticated Yeast

Messenger RNA(mRNA)is a chain of ribonucleotide molecules that conveys genetic information from DNA to the protein.As a key node of the central dogma of molecular biology,it plays a leading role in this transmission.With the emergence of novel modern molecular biology techniques,the researchers defined that mRNA is similar to other single-stranded RNA molecules that adopt Watson-Crick base pairs to fold into exquisite secondary structure locally,and mRNA secondary structure plays a crucial role in the regulation of expression,especially influencing translation efficiency.Functional importance brings about evolutionary conservation.Previous researches have a growing appreciation of the conserved mRNA structure across lineages of different species,indicating that purifing selection can remove deleterious mutations in the population due to the functional constraints imposed on mRNA secondary structure.However,when a mutation changes mRNA secondary structure,the translation efficiency could be up-or down-regulated,which is likely to improve the fitness of the individual.It is conducive to the adaption of the dramatic environment alterations,and the beneficial alleles can spread among the population and even be fixed eventually.Until now,there is no explicit evidence about the nature,pattern,distribution,and strength of positive selection on mRNA secondary structure.Here,we construct a large-scale dataset of single nucleotide polymorphisms(SNPs)at synonymous sites in the population of 128 yeast strains(Saccharomyces cerevisiae),combined with the experimental assessment of mRNA structure.Furthermore,we perform empirical population genetics data analysis through unfolded site-frequency spectra and describe the type and strength of positive selection quantitatively by Poisson Random Field model.Different from other site-specific models,like dn/ds,this population genetic-based analysis of selection under Poisson Random Field(PRF)framework operating within a single species in our study can be extended to detect selection on untranslated regions or synonymous sites.To rule out the influence of deviation such as sequencing errors or ancestral identification,our study also constructed multiple groups of yeasts for auxiliary verification.Our results show that mRNA secondary structure is subject to positive selection widespread among the genome.The pattern of selection is that the stem in mRNA(especially the coding region)tends to accumulate more GC nucleotides,which is greatly affected by the mRNA stem length.At the synonymous site without codon usage bias,this kind of positive selection still exists.In addition,this pattern of adaptive evolution widely exists in yeast genome,particularly in those genes related to mitochondria activities.We speculate that it is aimed to achieve a balance between cellular respiration and alcoholic fermentation precisely,due to adjusting to the changes from wild to man-made environments during the domestication.This study not only greatly supplements the evolutionary evidence of non-protein level translational regulation,but also provides a new perspective for understanding the phenomenon of artificial domestication.