Evidence from Drosophila Supports Higher Duplicability of Faster Evolving Genes.
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ABSTRACT:
SUBMITTER: Vance Z
PROVIDER: S-EPMC8765793 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:An attractive and long-standing hypothesis regarding the evolution of genes after duplication posits that the duplication event creates new evolutionary possibilities by releasing a copy of the gene from constraint. Apparent support was found in numerous analyses, particularly, the observation of higher rates of evolution in duplicated as compared with singleton genes. Could it, instead, be that more duplicable genes (owing to mutation, fixation, or retention biases) are intrinsically faster evolving? To uncouple the measurement of rates of evolution from the determination of duplicate or singleton status, we measure the rates of evolution in singleton genes in outgroup primate lineages but classify these genes as to whether they have duplicated or not in a crown group of great apes. We find that rates of evolution are higher in duplicable genes prior to the duplication event. In part this is owing to a negative correlation between coding sequence length and rate of evolution, coupled with a bias toward smaller genes being more duplicable. The effect is masked by difference in expression rate between duplicable genes and singletons. Additionally, in contradiction to the classical assumption, we find no convincing evidence for an increase in dN/dS after duplication, nor for rate asymmetry between duplicates. We conclude that high rates of evolution of duplicated genes are not solely a consequence of the duplication event, but are rather a predictor of duplicability. These results are consistent with a model in which successful gene duplication events in mammals are skewed toward events of minimal phenotypic impact.
| S-EPMC5850500 | biostudies-literature
Project description:BACKGROUND: There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS: We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS: Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.
| S-EPMC2894830 | biostudies-literature
Project description:In an attempt to quantify the rates of protein sequence divergence in Drosophila, we have devised a screen to differentiate between slow and fast evolving genes. We find that over one-third of randomly drawn cDNAs from a Drosophila melanogaster library do not cross-hybridize with Drosophila virilis DNA, indicating that they evolve with a very high rate. To determine the evolutionary characteristics of such protein sequences, we sequenced their homologs from a more closely related species (Drosophila yakuba). The amino acid substitution rates among these cDNAs are among the fastest known and several are only about 2-fold lower than the corresponding values for silent substitutions. An analysis of within-species polymorphisms for one of these sequences reveals an exceptionally high number of polymorphic amino acid positions, indicating that the protein is not under strong negative selection. We conclude that the Drosophila genome harbors a substantial proportion of genes with a very high divergence rate.
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Project description:BACKGROUND: Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in the coding portion of paralogs and about asymmetry of these rates. RESULTS: We analyse sequence evolution asymmetry in paralogs present in 12 Drosophila genomes using the nearest non-duplicated orthologous outgroup as a reference. Those paralogs present in D. melanogaster are analysed in conjunction with the asymmetry of expression rate and ubiquity and of segregating non-synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions, on average, faster than their nearest singleton orthologs. The distribution of paralogs' substitution rate asymmetry is overdispersed relative to that of orthologous clades, containing disproportionally more unusually symmetric and unusually asymmetric clades. We show that paralogs are more asymmetric in: a) clades orthologous to highly constrained singleton genes; b) genes with high expression level; c) genes with ubiquitous expression and d) non-tandem duplications. We further demonstrate that, in each asymmetrically evolving pair of paralogs, the faster evolving member of the pair tends to have lower average expression rate, lower expression uniformity and higher frequency of non-synonymous SNPs than its slower evolving counterpart. CONCLUSIONS: Our findings are consistent with the hypothesis that many duplications in Drosophila are retained despite stabilising selection being more relaxed in one of the paralogs than in the other, suggesting a widespread unfinished pseudogenization. This phenomenon is likely to make detection of neo- and subfunctionalization signatures difficult, as these models of duplication retention also predict asymmetries in substitution rates and expression profiles.
| S-EPMC3906896 | biostudies-other
Project description:The mechanism by which protein functional diversity expands is an important evolutionary issue. Studies of recently evolved chimeric genes permit direct investigation of the origin of new protein functions before they become obscured by subsequent evolution. Found in several African Drosophila species, jingwei (jgw), a recently evolved gene with a domain derived from the still extant short-chain alcohol dehydrogenase (ADH) through retroposition, provides an opportunity to examine this previously undescribed process directly. We expressed JGW proteins in a microbial expression system and, after purification, investigated their enzymatic properties. We found that, unexpectedly, positive Darwinian selection for amino acid replacements outside the active site of JGW produced a novel dehydrogenase with altered substrate specificity compared with the ancestral ADH. Instead of detoxifying and assimilating ethanol like its Adh parental gene, we observe that JGW efficiently utilizes long-chain primary alcohols found in hormone and pheromone metabolism. These data suggest that protein functional diversity can expand rapidly under the joint forces of exon shuffling, gene duplication, and natural selection.
| S-EPMC528974 | biostudies-literature
Project description:Purifying selection often results in conservation of gene sequence and function. The most functionally conserved genes are also thought to be among the most biologically essential. These observations have led to the use of sequence conservation as a proxy for functional conservation. Here we describe two genes that are exceptions to this pattern. We show that lack of sequence conservation among orthologs of CG15460 and CG15323-herein named jean-baptiste (jb) and karr, respectively-does not necessarily predict lack of functional conservation. These two Drosophila melanogaster genes are among the most rapidly evolving protein-coding genes in this species, being nearly as diverged from their D. yakuba orthologs as random sequences are. jb and karr are both expressed at an elevated level in larval males and adult testes, but they are not accessory gland proteins and their loss does not affect male fertility. Instead, knockdown of these genes in D. melanogaster via RNA interference caused male-biased viability defects. These viability effects occur prior to the third instar for jb and during late pupation for karr. We show that putative orthologs to jb and karr are also expressed strongly in the testes of other Drosophila species and have similar gene structure across species despite low levels of sequence conservation. While standard molecular evolution tests could not reject neutrality, other data hint at a role for natural selection. Together these data provide a clear case where a lack of sequence conservation does not imply a lack of conservation of expression or function.
| S-EPMC3880551 | biostudies-literature
Project description:Characterizing the distribution of selection coefficients in natural populations remains a central challenge in evolutionary biology. We resequenced a subset of 19 fast-evolving protein-coding genes in the sister species Drosophila miranda and D. pseudoobscura and their flanking regions to characterize the spatial footprint left by recurrent and recent selection. Consistent with previous findings, fast-evolving genes and their flanking regions show reduced levels of neutral diversity compared with randomly chosen genes, as expected under recurrent selection models. Applying a variety of statistical tests designed for the detection of selection at different evolutionary timescales, we attempt to characterize parameters of adaptive evolution. In D. miranda, fast-evolving genes generally show evidence of increased rates of adaptive evolution relative to random genes, whereas this pattern is somewhat less pronounced in D. pseudoobscura. Our results suggest that fast-evolving genes are not characterized by significantly different selection coefficients but rather a shift in the distribution of the rate of fixation.
| S-EPMC2943246 | biostudies-literature
Project description:The egg-laying hormone ovulin (Acp26Aa) is among the most rapidly evolving proteins in the Drosophila genome. Against the background of ovulin's high sequence variability within and between species, we have identified highly conserved motifs that may play an important structural role. Using yeast two-hybrid and GST-pull-down assays, we show that ovulin interacts with itself. The C terminus of ovulin is necessary and sufficient for self-interaction, with its C-terminal 45 aa playing a major role. Under nonreducing conditions, ovulin participates in a high-molecular-mass complex, suggesting that it occurs in an oligomeric form. One or more of three predicted coiled-coil domains in the C terminus of ovulin may be involved in its self-interaction. These structural elements are conserved between species despite an overall rapid pace of evolution in ovulin's primary sequence. We therefore suggest that domains involved in ovulin's self-interaction form a conserved structural backbone for the protein, resulting in greater evolutionary flexibility at other sites.
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Project description:Understanding the causes of vaccine failure is important for predicting disease dynamics in vaccinated populations and planning disease interventions. Pathogen exposure dose and heterogeneity in host susceptibility have both been implicated as important factors that may reduce overall vaccine efficacy and cause vaccine failure. Here, we explore the effect of pathogen dose and heterogeneity in host susceptibility in reducing efficacy of vaccines. Using simulation-based methods, we find that increases in pathogen exposure dose decrease vaccine efficacy, but this effect is modified by heterogeneity in host susceptibility. In populations where the mode of vaccine action is highly polarized, vaccine efficacy decreases more slowly with exposure dose than in populations with less variable protection. We compared these theoretical results to empirical estimates from a systematic literature review of vaccines tested over multiple exposure doses. We found that few studies (nine of 5,389) tested vaccine protection against infection over multiple pathogen challenge doses, with seven studies demonstrating a decrease in vaccine efficacy with increasing exposure dose. Our research demonstrates that pathogen dose has potential to be an important determinant of vaccine failure, although the limited empirical data highlight a need for additional studies to test theoretical predictions on the plausibility of reduced host susceptibility and high pathogen dose as mechanisms responsible for reduced vaccine efficacy in high transmission settings.
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Project description:As genomic sequences become easier to acquire, shotgun proteomics will play an increasingly important role in genome annotation. With proteomics, researchers can confirm and revise existing genome annotations and discover completely new genes. Proteomic-based de novo gene discovery should be especially useful for sets of genes with characteristics that make them difficult to predict with gene-finding algorithms. Here, we report the proteomic discovery of 19 previously unannotated genes encoding seminal fluid proteins (Sfps) that are transferred from males to females during mating in Drosophila. Using bioinformatics, we detected putative orthologs of these genes, as well as 19 others detected by the same method in a previous study, across several related species. Gene expression analysis revealed that nearly all predicted orthologs are transcribed and that most are expressed in a male-specific or male-biased manner. We suggest several reasons why these genes escaped computational prediction. Like annotated Sfps, many of these new proteins show a pattern of adaptive evolution, consistent with their potential role in influencing male sperm competitive ability. However, in contrast to annotated Sfps, these new genes are shorter, have a higher rate of nonsynonymous substitution, and have a markedly lower GC content in coding regions. Our data demonstrate the utility of applying proteomic gene discovery methods to a specific biological process and provide a more complete picture of the molecules that are critical to reproductive success in Drosophila.
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