Rapid sequence evolution is associated with genetic incompatibilities in the plastid Clp complex

The plastid caseinolytic protease (Clp) complex plays essential roles in maintaining protein homeostasis and comprises both plastid-encoded and nuclear-encoded subunits. Despite the Clp complex being retained across green plants with highly conserved protein sequences in most species, examples of extremely accelerated amino acid substitution rates have been identified in numerous angiosperms. The causes of these accelerations have been the subject of extensive speculation but still remain unclear. To distinguish among prevailing hypotheses and begin to understand the functional consequences of rapid sequence divergence in Clp subunits, we used plastome transformation to replace the native clpP1 gene in tobacco (Nicotiana tabacum) with counterparts from another angiosperm genus (Silene) that exhibits a wide range in rates of Clp protein sequence evolution. We found that antibiotic-mediated selection could drive a transgenic clpP1 replacement from a slowly evolving donor species (S. latifolia) to homoplasmy but that clpP1 copies from Silene species with accelerated evolutionary rates remained heteroplasmic, meaning that they could not functionally replace the essential tobacco clpP1 gene. These results suggest that observed cases of rapid Clp sequence evolution are a source of epistatic incompatibilities that must be ameliorated by coevolutionary responses between plastid and nuclear subunits.

The constraints between amino acids influence the unequal distribution of codons and protein sequence evolution

Four nucleotides (A, U, C and G) constitute 64 codons at free combination but 64 codons are unequally assigned to 21 items (20 amino acids plus one stop). About 500 amino acids are known but only 20 are selected to make up the proteins. However, the relationships between amino acid and codon and between 20 amino acids have been unclear. In this paper, we studied the relationships between 20 amino acids in 33 species and found there were three constraints between 20 amino acids, such as the relatively stable mean carbon and hydrogen (C : H) ratios (0.50), similarity interactions between the constituent ratios of amino acids, and the frequency of amino acids according with Poisson distribution under certain conditions. We demonstrated that the unequal distribution of 64 codons and the choice of amino acids in molecular evolution would be constrained to remain stable C : H ratios. The constituent ratios and frequency of 20 amino acids in a species or a protein are two determinants of protein sequence evolution, so this finding showed the constraints between 20 amino acids played an important role in protein sequence evolution.

The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes

The development of explanatory models of protein sequence evolution has broad implications for our understanding of cellular biology, population history, and disease etiology. Here we analyze the GTEx transcriptome resource to quantify the effect of the transcriptome on protein sequence evolution in a multi-tissue framework. We find substantial variation among the central nervous system tissues in the effect of expression variance on evolutionary rate, with highly variable genes in the cortex showing significantly greater purifying selection than highly variable genes in subcortical regions (Mann–Whitney U p = 1.4 × 10−4). The remaining tissues cluster in observed expression correlation with evolutionary rate, enabling evolutionary analysis of genes in diverse physiological systems, including digestive, reproductive, and immune systems. Importantly, the tissue in which a gene attains its maximum expression variance significantly varies (p = 5.55 × 10−284) with evolutionary rate, suggesting a tissue-anchored model of protein sequence evolution. Using a large-scale reference resource, we show that the tissue-anchored model provides a transcriptome-based approach to predicting the primary affected tissue of developmental disorders. Using gradient boosted regression trees to model evolutionary rate under a range of model parameters, selected features explain up to 62% of the variation in evolutionary rate and provide additional support for the tissue model. Finally, we investigate several methodological implications, including the importance of evolutionary-rate-aware gene expression imputation models using genetic data for improved search for disease-associated genes in transcriptome-wide association studies. Collectively, this study presents a comprehensive transcriptome-based analysis of a range of factors that may constrain molecular evolution and proposes a novel framework for the study of gene function and disease mechanism.

Sex-biased genes expressed in the cricket brain evolve rapidly

BackgroundSex-biased gene expression, particularly male-biased expression in the gonad, has often been linked to rapid protein sequence evolution (dN/dS) in animals. This evolutionary trend may arise from one or both of sexual selection pressures during mating or low pleiotropy. In insects, research on sex-biased transcription and dN/dS remains largely focused on a few holometabolous species, with variable findings on male and female gonadal effects. The brain is central to the mating process, and provides neurological foundation for mating behaviors, such as courtship, intrasex competition and mate choice. However, there is a striking paucity of research on sex-biased expression of genes in the brain and the rate of protein sequence evolution in such genes.ResultsHere, we studied sex-biased gene expression in a hemimetabolous insect, the cricket Gryllus bimaculatus. We generated novel RNA-seq data for two sexual tissue types, the gonad and somatic reproductive system, and for two core components of the nervous system, the brain and ventral nerve cord. From a genome-wide analysis of genes expressed in these tissues, we report the accelerated evolution of testis-biased genes and seminal fluid proteins (SFPs) genes, as compared to ovary-biased and unbiased genes in this cricket model, which includes an elevated frequency of positive selection events. With respect to the brain, while sex-biased brain genes were much less common than for the gonads, they exhibited exceptionally rapid evolution, an effect that was stronger for the female than for the male brain. Certain sex-biased brain genes were predicted to be involved in mating or sex-related functions, which we suggest may cause exposure to sexual selection. Moreover, the sex-biased brain genes exhibited remarkably low cross-tissue expression breadth, or pleiotropy. We speculate that this feature may permit relaxed purifying selection, and allow the freedom for adaptive protein functional changes in these brain-expressed genes.ConclusionsOur results demonstrate that sex-biased expression in the male gonad, and sex-biased gene expression in the brain, especially the female brain, are associated with rapid protein sequence evolution in a cricket model system. We discuss the results with respect to our findings on pleiotropy and positive selection, and consider the potential role of the dynamic mating biology of this cricket model in shaping these patterns.

The constraints between amino acids influence the unequal distribution of codons and protein sequence evolution

4 nucleotides(A, U, C, G) constitute 64 codons at free combination but 64 codons are unequally assigned to 21 items (20 amino acids plus one stop). About 500 amino acids are known but only 20 ones are selected to make up the proteins. However, the relationships between amino acid and codon and between 20 amino acids have been unclear. In this paper, we studied on the relationships between 20 amino acids in 33 species and found there were three constraints between 20 amino acids, such as the relatively stable mean carbon and hydrogen(C:H) ratios(0.50), similarity interactions between the constituent ratios of amino acids, and the frequency of amino acids according with Poisson distribution under a certain conditions. We demonstrated that the unequal distribution of 64 codons and the choice of amino acids in molecular evolution would be constrained to remain stable C:H ratios. The constituent ratios and frequency of 20 amino acids in a species or a protein are two determinants of protein sequence evolution, so this findings showed the constraints between 20 amino acids played an important role in protein sequence evolution.

Protein evolution is structure dependent and non-homogeneous across the tree of life

MotivationProtein sequence evolution is a complex process that varies among-sites within proteins and across the tree of life. Comparisons of evolutionary rate matrices for specific taxa (‘clade-specific models’) have the potential to reveal this variation and provide information about the underlying reasons for those changes. To study changes in patterns of protein sequence evolution we estimated and compared clade-specific models in a way that acknowledged variation within proteins due to structure.ResultsClade-specific model fit was able to correctly classify proteins from four specific groups (vertebrates, plants, oomycetes, and yeasts) more than 70% of the time. This was true whether we used mixture models that incorporate relative solvent accessibility or simple models that treat sites as homogeneous. Thus, protein evolution is non-homogeneous over the tree of life. However, a small number of dimensions could explain the differences among models (for mixture models ~50% of the variance reflected relative solvent accessibility and ~25% reflected clade). Relaxed purifying selection in taxa with lower long-term effective population sizes appears to explain much of the among clade variance. Relaxed selection on solvent-exposed sites was correlated with changes in amino acid side-chain volume; other differences among models were more complex. Beyond the information they reveal about protein evolution, our clade-specific models also represent tools for phylogenomic inference.AvailabilityModel files are available from https://github.com/ebraun68/[email protected] informationSupplementary data are appended to this preprint.

A common root for coevolution and substitution rate variability in protein sequence evolution

We introduce a simple model that describes the average occurrence of point variations in a generic protein sequence. This model is based on the idea that mutations are more likely to be fixed at sites in contact with others that have mutated in the recent past. Therefore, we extend the usual assumptions made in protein coevolution by introducing a time dumping on the effect of a substitution on its surrounding and makes correlated substitutions happen in avalanches localized in space and time. The model correctly predicts the average correlation of substitutions as a function of their distance along the sequence. At the same time, it predicts an among-site distribution of the number of substitutions per site highly compatible with a negative binomial, consistently with experimental data. The promising outcomes achieved with this model encourage the application of the same ideas in the field of pairwise and multiple sequence alignment.