Maintenance of duplicate genes and their functional redundancy by reduced expression.
Ontology highlight
ABSTRACT:
SUBMITTER: Qian W
PROVIDER: S-EPMC2942974 | biostudies-literature | 2010 Oct
REPOSITORIES: biostudies-literature
Publications
Maintenance of duplicate genes and their functional redundancy by reduced expression.
Qian Wenfeng W Liao Ben-Yang BY Chang Andrew Ying-Fei AY Zhang Jianzhi J
Trends in genetics : TIG 20100812 10
Although evolutionary theories predict functional divergence between duplicate genes, many old duplicates still maintain a high degree of functional similarity and are synthetically lethal or sick, an observation that has puzzled many geneticists. We propose that expression reduction, a special type of subfunctionalization, facilitates the retention of duplicates and the conservation of their ancestral functions. Consistent with this hypothesis, gene expression data from both yeasts and mammals ...[more]
Similar Datasets
Project description:BackgroundThe imprint of natural selection on gene sequences is often difficult to detect. A plethora of methods have been devised to detect genetic changes due to selective processes. However, many of those methods depend heavily on underlying assumptions regarding the mode of change of DNA sequences and often require sophisticated mathematical treatments that made them computationally slow. The development of fast and effective methods to detect modifications in the selective constraints of genes is therefore of great interest.ResultsWe describe UVPAR, a program designed to quickly test for changes in the functional constraints of duplicate genes. Starting with alignments of the proteins encoded by couples of duplicate genes in two different species, UVPAR detects the regions in which modifications of the functional constraints in the paralogs occurred since both species diverged. Sequences can be analyzed with UVPAR in just a few minutes on a standard PC computer. To demonstrate the power of the program, we first show how the results obtained with UVPAR compare to those based on other approaches, using data for vertebrate Hox genes. We then describe a comprehensive study of the RBR family of ubiquitin ligases in which we have performed 529 analyses involving 14 duplicate genes in seven model species. A significant increase in the number of functional shifts was observed for the species Danio rerio and for the gene Ariadne-2.ConclusionThese results show that UVPAR can be used to generate sensitive analyses to detect changes in the selection constraints acting on paralogs. The high speed of the program allows its application to genome-scale analyses.
| S-EPMC1570150 | biostudies-literature
Project description:We examined the evolution of expression of duplicate genes in Arabidopsis thaliana, by analyzing 512 data sets of gene expression microarrays and 2022 recent duplicate gene pairs. Expression divergence between gene duplicates is significantly greater in response to environmental stress than to developmental processes. A slow rate of expression divergence during development might offer dosage-dependent selective advantage, whereas rapid expression divergence in response to external changes might accelerate adaptation.
| S-EPMC2065749 | biostudies-literature
Project description:Knocking out a gene from a genome often causes no phenotypic effect. This phenomenon has been explained in part by the existence of duplicate genes. However, it was found that in mouse knockout data duplicate genes are as essential as singleton genes. Here, we study whether it is also true for the knockout data in Arabidopsis. From the knockout data in Arabidopsis thaliana obtained in our study and in the literature, we find that duplicate genes show a significantly lower proportion of knockout effects than singleton genes. Because the persistence of duplicate genes in evolution tends to be dependent on their phenotypic effect, we compared the ages of duplicate genes whose knockout mutants showed less severe phenotypic effects with those with more severe effects. Interestingly, the latter group of genes tends to be more anciently duplicated than the former group of genes. Moreover, using multiple-gene knockout data, we find that functional compensation by duplicate genes for a more severe phenotypic effect tends to be preserved by natural selection for a longer time than that for a less severe effect. Taken together, we conclude that duplicate genes contribute to genetic robustness mainly by preserving compensation for severe phenotypic effects in A. thaliana.
| S-EPMC2817435 | biostudies-literature
Project description:Many genes can be deleted with little phenotypic consequences. By what mechanism and to what extent the presence of duplicate genes in the genome contributes to this robustness against deletions has been the subject of considerable interest. Here, we exploit the availability of high-density genetic interaction maps to provide direct support for the role of backup compensation, where functionally overlapping duplicates cover for the loss of their paralog. However, we find that the overall contribution of duplicates to robustness against null mutations is low ( approximately 25%). The ability to directly identify buffering paralogs allowed us to further study their properties, and how they differ from non-buffering duplicates. Using environmental sensitivity profiles as well as quantitative genetic interaction spectra as high-resolution phenotypes, we establish that even duplicate pairs with compensation capacity exhibit rich and typically non-overlapping deletion phenotypes, and are thus unable to comprehensively cover against loss of their paralog. Our findings reconcile the fact that duplicates can compensate for each other's loss under a limited number of conditions with the evolutionary instability of genes whose loss is not associated with a phenotypic penalty.
| S-EPMC1847942 | biostudies-literature
Project description:BackgroundGene duplication is the primary source of new genes with novel or altered functions. It is known that duplicates may obtain these new functional roles by evolving divergent expression patterns and/or protein functions after the duplication event. Here, using yeast (Saccharomyces cerevisiae) as a model organism, we investigate a previously little considered mode for the functional diversification of duplicate genes: subcellular adaptation of encoded proteins.ResultsWe show that for 24-37% of duplicate gene pairs derived from the S. cerevisiae whole-genome duplication event, the two members of the pair encode proteins that localize to distinct subcellular compartments. The propensity of yeast duplicate genes to evolve new localization patterns depends to a large extent on the biological function of their progenitor genes. Proteins involved in processes with a wider subcellular distribution (for example, catabolism) frequently evolved new protein localization patterns after duplication, whereas duplicate proteins limited to a smaller number of organelles (for example, highly expressed biosynthesis/housekeeping proteins with a slow rate of evolution) rarely relocate within the cell. Paralogous proteins evolved divergent localization patterns by partitioning of ancestral localizations ('sublocalization'), but probably more frequently by relocalization to new compartments ('neolocalization'). We show that such subcellular reprogramming may occur through selectively driven substitutions in protein targeting sequences. Notably, our data also reveal that relocated proteins functionally adapted to their new subcellular environments and evolved new functional roles through changes of their physico-chemical properties, expression levels, and interaction partners.ConclusionWe conclude that protein subcellular adaptation represents a common mechanism for the functional diversification of duplicate genes.
| S-EPMC2397506 | biostudies-literature
Project description:Gene duplication is thought to play a major role in phenotypic evolution. Yet the forces involved in the functional divergence of young duplicate genes remain unclear. Here, we use population-genetic inference to elucidate the role of natural selection in the functional evolution of young duplicate genes in Drosophila melanogaster. We find that negative selection acts on young duplicates with ancestral functions, and positive selection on those with novel functions, suggesting that natural selection may determine whether and how young duplicate genes are retained. Moreover, evidence of natural selection is strongest in protein-coding regions and 3' UTRs of young duplicates, indicating that selection may primarily target encoded proteins and regulatory sequences specific to 3' UTRs. Further analysis reveals that natural selection acts immediately after duplication and weakens over time, possibly explaining the observed bias toward the acquisition of new functions by young, rather than old, duplicate gene copies. Last, we find an enrichment of testis-related functions in young duplicates that underwent recent positive selection, but not in young duplicates that did not undergo recent positive selection, or in old duplicates that either did or did not undergo recent positive selection. Thus, our findings reveal that natural selection is a key player in the functional evolution of young duplicate genes, acts rapidly and in a region-specific manner, and may underlie the origin of novel testis-specific phenotypes in Drosophila.
| S-EPMC5850746 | biostudies-literature
Project description:Polyploidy or whole genome duplication (WGD) provides raw genetic materials for sequence and expression evolution of duplicate genes. However, the mode and tempo of expression divergence between WGD duplicate genes in closely related species and recurrent allopolyploids are poorly understood. Arabidopsis is a suitable system for testing the hypothesis that duplicate genes increase expression diversity and regulatory networks. In Arabidopsis, WGD occurred more than once before the split between Arabidopsis thaliana and Arabidopsis arenosa, and both natural and human-made allotetraploids are available. Comparative genomic hybridization analysis indicated that single-copy and duplicate genes after WGD were well preserved in A. thaliana and A. arenosa. Analysis of gene expression microarrays showed that duplicate genes generally had higher levels of expression divergence between two closely related species than single-copy genes. The proportion of the progenitors' duplicate genes that were nonadditively expressed in the resynthesized and natural allotetraploids was significantly higher than that of single-copy genes. Duplicate genes related to environmental stresses tended to be differentially expressed, and multicopy duplicate genes were likely to diverge expression between progenitors and in the allotetraploids. Compared with single-copy genes, duplicate genes tended to contain TATA boxes and less DNA methylation in the promoter regions, facilitating transcriptional regulation by binding transcription factors and/or cis- and trans-acting proteins. The data suggest an important role of WGD duplicate genes in modulating diverse and novel gene expression changes in response to external environmental cues and internal genetic turmoil such as recurrent polyploidy events.
| S-EPMC2650150 | biostudies-literature
Project description:Lineage-specific duplicated genes likely contribute to the phenotypic divergence in closely related species. However, neither the frequency of duplication events nor the degree of selection pressures immediately after gene duplication is clear in the speciation process. Here, using Illumina DNA-sequencing reads from Arabidopsis halleri, which has multiple closely related species with high-quality genome assemblies (A. thaliana and A. lyrata), we succeeded in generating orthologous gene groups in Brassicaceae. The duplication frequency of retained genes in the Arabidopsis lineage was ?10 times higher than the duplication frequency inferred by comparative genomics of Arabidopsis, poplar, rice and moss (Physcomitrella patens). The difference of duplication frequencies can be explained by a rapid decay of anciently duplicated genes. To examine the degree of selection pressure on genes duplicated in either the A. halleri-lyrata or the A. halleri lineage, we examined positive and purifying selection in the A. halleri-lyrata and A. halleri lineages throughout the ratios of nonsynonymous to synonymous substitution rates (KA/KS). Duplicate genes tended to have a higher proportion of positive selection compared with non-duplicated genes. Interestingly, we found that functional divergence of duplicated genes was accelerated several million years after gene duplication compared with immediately after gene duplication.
| S-EPMC6014284 | biostudies-literature
Project description:It is well known that knocking out a gene in an organism often causes no phenotypic effect. One possible explanation is the existence of duplicate genes; that is, the effect of knocking out a gene is compensated by a duplicate copy. Another explanation is the existence of alternative pathways. In terms of metabolic products, the relative roles of the two mechanisms have been extensively studied in yeast but not in any multi-cellular organisms. Here, to address the functional compensation of metabolic products by duplicate genes, we quantified 35 metabolic products from 1,976 genes in knockout mutants of Arabidopsis thaliana by a high-throughput Liquid chromatography-Mass spectrometer (LC-MS) analysis. We found that knocking out either a singleton gene or a duplicate gene with distant paralogs in the genome tends to induce stronger metabolic effects than knocking out a duplicate gene with a close paralog in the genome, indicating that only duplicate genes with close paralogs play a significant role in functional compensation for metabolic products in A. thaliana. To extend the analysis, we examined metabolic products with either high or low connectivity in a metabolic network. We found that the compensatory role of duplicate genes is less important when the metabolite has a high connectivity, indicating that functional compensation by alternative pathways is common in the case of high connectivity. In conclusion, recently duplicated genes play an important role in the compensation of metabolic products only when the number of alternative pathways is small.
| S-EPMC3002239 | biostudies-other
Project description:Gene and genome duplication fosters genetic novelty, but redundant gene copies would undergo mutational decay unless preserved via selective or neutral forces. Molecular mechanisms mediating duplicate preservation remain incompletely understood. Several recent studies showed an association between DNA methylation and expression divergence of duplicated genes and suggested a role of epigenetic mechanism in duplicate retention. Here, we compare genome-wide gene-body CG methylation (BCGM) and duplicate gene expression between a rice mutant null for OsMet1-2(a major CG methytransferase in rice) and its isogenic wild-type. We demonstrate a causal link between BCGM divergence and expression difference of duplicate copies. Interestingly, the higher- and lower-expressing copies of duplicates as separate groups show broadly different responses with respect to direction of expression alteration upon loss of BCGM. A role for BCGM in conditioning expression divergence between copies of duplicates generally holds for duplicates generated by whole genome duplication (WGD) or by small-scale duplication processes. However, differences are evident among these categories, including a higher proportion of WGD duplicates manifesting expression alteration, and differential propensities to lose BCGM by the higher- and lower-expression copies in the mutant. Together, our results support the notion that differential epigenetic marking may facilitate long-term retention of duplicate genes.
| S-EPMC5453933 | biostudies-literature