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Andreas Wagner - One of the best experts on this subject based on the ideXlab platform.
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Pervasive Indels and Their Evolutionary Dynamics after the Fish-Specific Genome Duplication
Molecular biology and evolution, 2012Co-Authors: Baocheng Guo, Ming Zou, Andreas WagnerAbstract:Insertions and deletions (indels) in protein-coding Genes are important sources of genetic variation. Their role in creating new proteins may be especially important after gene duplication. However, little is known about how indels affect the divergence of Duplicate Genes. We here study thousands of Duplicate Genes in five fish (teleost) species with completely sequenced genomes. The ancestor of these species has been subject to a fish-specific genome duplication (FSGD) event that occurred approximately 350 Ma. We find that Duplicate Genes contain at least 25% more indels than single-copy Genes. These indels accumulated preferentially in the first 40 my after the FSGD. A lack of widespread asymmetric indel accumulation indicates that both members of a Duplicate gene pair typically experience relaxed selection. Strikingly, we observe a 30-80% excess of deletions over insertions that is consistent for indels of various lengths and across the five genomes. We also find that indels preferentially accumulate inside loop regions of protein secondary structure and in regions where amino acids are exposed to solvent. We show that Duplicate Genes with high indel density also show high DNA sequence divergence. Indel density, but not amino acid divergence, can explain a large proportion of the tertiary structure divergence between proteins encoded by Duplicate Genes. Our observations are consistent across all five fish species. Taken together, they suggest a general pattern of Duplicate gene evolution in which indels are important driving forces of evolutionary change.
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Duplicate Genes and robustness to transient gene knock downs in caenorhabditis elegans
Proceedings of The Royal Society B: Biological Sciences, 2004Co-Authors: Gavin C Conant, Andreas WagnerAbstract:We examine robustness to mutations in the nematode worm Caenorhabditis elegans and the role of singlecopy and Duplicate Genes in it. We do so by integrating complete genome sequence and microarray ...
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asymmetric sequence divergence of Duplicate Genes
Genome Research, 2003Co-Authors: Gavin C Conant, Andreas WagnerAbstract:Much like humans, gene Duplicates may be created equal, but they do not stay that way for long. For four completely sequenced genomes we show that 20%-30% of Duplicate gene pairs show asymmetric evolution in the amino acid sequence of their protein products. That is, one of the Duplicates evolves much faster than the other. The greater this asymmetry, the greater the ratio Ka/Ks of amino acid substitutions (Ka) to silent substitutions (Ks) in a gene pair. This indicates that most asymmetric divergence may be caused by relaxed selective constraints on one of the Duplicates. However, we also find some candidate Duplicates where positive (directional) selection of beneficial mutations (Ka/Ks > 1) may play a role in asymmetric divergence. Our analysis rests on a codon-based model of molecular evolution that allows a test for asymmetric divergence in Ka. The method is also more sensitive in detecting positive selection (Ka/Ks > 1) than models relying only on pairwise gene comparisons.
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asymmetric functional divergence of Duplicate Genes in yeast
Molecular Biology and Evolution, 2002Co-Authors: Andreas WagnerAbstract:Most Duplicate Genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Here, I present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one Duplicate usually shows significantly more molecular or genetic interactions than the other. I propose a model that can explain this divergence pattern if asymmetrically diverging Duplicate gene pairs show increased robustness to deleterious mutations.
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the yeast protein interaction network evolves rapidly and contains few redundant Duplicate Genes
Molecular Biology and Evolution, 2001Co-Authors: Andreas WagnerAbstract:In this paper, the structure and evolution of the protein interaction network of the yeast Saccharomyces cerevisiae is analyzed. The network is viewed as a graph whose nodes correspond to proteins. Two proteins are connected by an edge if they interact. The network resembles a random graph in that it consists of many small subnets (groups of proteins that interact with each other but do not interact with any other protein) and one large connected subnet comprising more than half of all interacting proteins. The number of interactions per protein appears to follow a power law distribution. Within approximately 200 Myr after a duplication, the products of Duplicate Genes become almost equally likely to (1) have common protein interaction partners and (2) be part of the same subnetwork as two proteins chosen at random from within the network. This indicates that the persistence of redundant interaction partners is the exception rather than the rule. After gene duplication, the likelihood that an interaction gets lost exceeds 2.2 x 10(-3)/Myr. New interactions are estimated to evolve at a rate that is approximately three orders of magnitude smaller. Every 300 Myr, as many as half of all interactions may be replaced by new interactions.
Chuanzhu Fan - One of the best experts on this subject based on the ideXlab platform.
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evolutionary fates and dynamic functionalization of young Duplicate Genes in arabidopsis genomes
Plant Physiology, 2016Co-Authors: Jun Wang, Feng Tao, Nicholas C Marowsky, Chuanzhu FanAbstract:Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of Duplicate Genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young Duplicate Genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella Based on the quantitative analysis metrics, we investigated the evolutionary processes of young Duplicate Genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young Duplicate Genes. We explicitly demonstrated the dynamic functionalization of Duplicate Genes along the evolutionary time scale. Upon origination, Duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant Duplicate Genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, Duplicate Genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young Duplicate Genes in plant genomes.
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divergence of gene body dna methylation and evolution of plant Duplicate Genes
PLOS ONE, 2014Co-Authors: Jun Wang, Nicholas C Marowsky, Chuanzhu FanAbstract:It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between Duplicate Genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of Duplicate Genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous Genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for Duplicate Genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.
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divergent evolutionary and expression patterns between lineage specific new Duplicate Genes and their parental paralogs in arabidopsis thaliana
PLOS ONE, 2013Co-Authors: Jun Wang, Nicholas C Marowsky, Chuanzhu FanAbstract:Gene duplication is an important mechanism for the origination of functional novelties in organisms. We performed a comparative genome analysis to systematically estimate recent lineage specific gene duplication events in Arabidopsis thaliana and further investigate whether and how these new Duplicate Genes (NDGs) play a functional role in the evolution and adaption of A. thaliana. We accomplished this using syntenic relationship among four closely related species, A. thaliana, A. lyrata, Capsella rubella and Brassica rapa. We identified 100 NDGs, showing clear origination patterns, whose parental Genes are located in syntenic regions and/or have clear orthologs in at least one of three outgroup species. All 100 NDGs were transcribed and under functional constraints, while 24% of the NDGs have differential expression patterns compared to their parental Genes. We explored the underlying evolutionary forces of these paralogous pairs through conducting neutrality tests with sequence divergence and polymorphism data. Evolution of about 15% of NDGs appeared to be driven by natural selection. Moreover, we found that 3 NDGs not only altered their expression patterns when compared with parental Genes, but also evolved under positive selection. We investigated the underlying mechanisms driving the differential expression of NDGs and their parents, and found a number of NDGs had different cis-elements and methylation patterns from their parental Genes. Overall, we demonstrated that NDGs acquired divergent cis-elements and methylation patterns and may experience sub-functionalization or neo-functionalization influencing the evolution and adaption of A. thaliana.
Jianzhi Zhang - One of the best experts on this subject based on the ideXlab platform.
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maintenance of Duplicate Genes and their functional redundancy by reduced expression
Trends in Genetics, 2010Co-Authors: Wenfeng Qian, Benyang Liao, Andrew Yingfei Chang, Jianzhi ZhangAbstract: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 show a substantial decrease in the level of gene expression after duplication. Whereas the majority of the expression reductions are likely to be neutral, some are apparently beneficial to rebalancing gene dosage after duplication.
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protein subcellular relocalization in the evolution of yeast singleton and Duplicate Genes
Genome Biology and Evolution, 2009Co-Authors: Wenfeng Qian, Jianzhi ZhangAbstract:Gene duplication is the primary source of new Genes, but the mechanisms underlying the functional divergence and retention of Duplicate Genes are not well understood. Because eukaryotic proteins are localized to subcellular structures and localization can be altered by a single amino acid replacement, it was recently proposed that protein subcellular relocalization (PSR) plays an important role in the functional divergence and retention of Duplicate Genes. Although numerous examples of distinct subcellular localizations of paralogous proteins have been reported, it is unknown whether PSR occurs more frequently after gene duplication than without duplication. By analyzing experimentally determined and computationally predicted genome-wide protein subcellular localization data of the budding yeast Saccharomyces cerevisiae and two other fungi (Schizosaccharomyces pombe and Kluyveromyces waltii), we show that even singleton Genes have an appreciable rate of relocalization in evolution and that Duplicate Genes do not relocalize more frequently than singletons. These results suggest that subcellular relocalization is unlikely to have been a major mechanism for Duplicate gene retention and functional divergence at the genomic scale.
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mouse Duplicate Genes are as essential as singletons
Trends in Genetics, 2007Co-Authors: Benyang Liao, Jianzhi ZhangAbstract:Duplicate Genes in mouse are widely thought to have functional redundancy, and to be less essential than singleton Genes. We analyzed nearly 3900 individually knocked out mouse Genes and discovered that the proportion of essential Genes is ∼55% in both singletons and Duplicates. This suggests that mammalian Duplicates rarely compensate for each other, and that the absence of phenotypes in mice deficient for a Duplicate gene should not be automatically attributed to paralogous compensation.
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transcriptional reprogramming and backup between Duplicate Genes is it a genomewide phenomenon
Genetics, 2006Co-Authors: Jianzhi ZhangAbstract:Deleting a Duplicate gene often results in a less severe phenotype than deleting a singleton gene, a phenomenon commonly attributed to functional compensation among Duplicates. However, Duplicate Genes rapidly diverge in expression patterns after duplication, making functional compensation less probable for ancient Duplicates. Case studies suggested that a gene may provide compensation by altering its expression upon removal of its Duplicate copy. On the basis of this observation and a genomic analysis, it was recently proposed that transcriptional reprogramming and backup among Duplicates is a genomewide phenomenon in the yeast Saccharomyces cerevisiae. Here we reanalyze the yeast data and show that the high dispensability of Duplicate Genes with low expression similarity is a consequence of expression similarity and gene dispensability, each being correlated with a third factor, the number of protein interactions per gene. There is little evidence supporting widespread functional compensation of divergently expressed Duplicate Genes by transcriptional reprogramming.
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rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in Duplicate gene evolution
Genetics, 2005Co-Authors: Xionglei He, Jianzhi ZhangAbstract:Gene duplication is the primary source of new Genes. Duplicate Genes that are stably preserved in genomes usually have divergent functions. The general rules governing the functional divergence, however, are not well understood and are controversial. The neofunctionalization (NF) hypothesis asserts that after duplication one daughter gene retains the ancestral function while the other acquires new functions. In contrast, the subfunctionalization (SF) hypothesis argues that Duplicate Genes experience degenerate mutations that reduce their joint levels and patterns of activity to that of the single ancestral gene. We here show that neither NF nor SF alone adequately explains the genome-wide patterns of yeast protein interaction and human gene expression for Duplicate Genes. Instead, our analysis reveals rapid SF, accompanied by prolonged and substantial NF in a large proportion of Duplicate Genes, suggesting a new model termed subneofunctionalization (SNF). Our results demonstrate that enormous numbers of new functions have originated via gene duplication.
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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evolutionary fates and dynamic functionalization of young Duplicate Genes in arabidopsis genomes
Plant Physiology, 2016Co-Authors: Jun Wang, Feng Tao, Nicholas C Marowsky, Chuanzhu FanAbstract:Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of Duplicate Genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young Duplicate Genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella Based on the quantitative analysis metrics, we investigated the evolutionary processes of young Duplicate Genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young Duplicate Genes. We explicitly demonstrated the dynamic functionalization of Duplicate Genes along the evolutionary time scale. Upon origination, Duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant Duplicate Genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, Duplicate Genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young Duplicate Genes in plant genomes.
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divergence of gene body dna methylation and evolution of plant Duplicate Genes
PLOS ONE, 2014Co-Authors: Jun Wang, Nicholas C Marowsky, Chuanzhu FanAbstract:It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between Duplicate Genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of Duplicate Genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous Genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for Duplicate Genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.
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divergent evolutionary and expression patterns between lineage specific new Duplicate Genes and their parental paralogs in arabidopsis thaliana
PLOS ONE, 2013Co-Authors: Jun Wang, Nicholas C Marowsky, Chuanzhu FanAbstract:Gene duplication is an important mechanism for the origination of functional novelties in organisms. We performed a comparative genome analysis to systematically estimate recent lineage specific gene duplication events in Arabidopsis thaliana and further investigate whether and how these new Duplicate Genes (NDGs) play a functional role in the evolution and adaption of A. thaliana. We accomplished this using syntenic relationship among four closely related species, A. thaliana, A. lyrata, Capsella rubella and Brassica rapa. We identified 100 NDGs, showing clear origination patterns, whose parental Genes are located in syntenic regions and/or have clear orthologs in at least one of three outgroup species. All 100 NDGs were transcribed and under functional constraints, while 24% of the NDGs have differential expression patterns compared to their parental Genes. We explored the underlying evolutionary forces of these paralogous pairs through conducting neutrality tests with sequence divergence and polymorphism data. Evolution of about 15% of NDGs appeared to be driven by natural selection. Moreover, we found that 3 NDGs not only altered their expression patterns when compared with parental Genes, but also evolved under positive selection. We investigated the underlying mechanisms driving the differential expression of NDGs and their parents, and found a number of NDGs had different cis-elements and methylation patterns from their parental Genes. Overall, we demonstrated that NDGs acquired divergent cis-elements and methylation patterns and may experience sub-functionalization or neo-functionalization influencing the evolution and adaption of A. thaliana.
Marc Robinsonrechavi - One of the best experts on this subject based on the ideXlab platform.
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selective constraints on coding sequences of nervous system Genes are a major determinant of Duplicate gene retention in vertebrates
Molecular Biology and Evolution, 2017Co-Authors: Marc Robinsonrechavi, Julien RouxAbstract:: The evolutionary history of vertebrates is marked by three ancient whole-genome duplications: two successive rounds in the ancestor of vertebrates, and a third one specific to teleost fishes. Biased loss of most Duplicates enriched the genome for specific Genes, such as slow evolving Genes, but this selective retention process is not well understood. To understand what drives the long-term preservation of Duplicate Genes, we characterized Duplicated Genes in terms of their expression patterns. We used a new method of expression enrichment analysis, TopAnat, applied to in situ hybridization data from thousands of Genes from zebrafish and mouse. We showed that the presence of expression in the nervous system is a good predictor of a higher rate of retention of Duplicate Genes after whole-genome duplication. Further analyses suggest that purifying selection against the toxic effects of misfolded or misinteracting proteins, which is particularly strong in nonrenewing neural tissues, likely constrains the evolution of coding sequences of nervous system Genes, leading indirectly to the preservation of Duplicate Genes after whole-genome duplication. Whole-genome duplications thus greatly contributed to the expansion of the toolkit of Genes available for the evolution of profound novelties of the nervous system at the base of the vertebrate radiation.
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evolutionary rates of Duplicate Genes in fish and mammals
Molecular Biology and Evolution, 2001Co-Authors: Marc Robinsonrechavi, Vincent LaudetAbstract:Recently, much attention has been attracted by the abundance of Duplicate Genes in teleost fish (Amores et al. 1998; Wittbrodt, Meyer, and Schartl 1998). It has been suggested that this abundance reflected an ancestral genome duplication and that it may be related to the great diversity of this group (Vogel 1998). Emphasizing the importance of gene duplication in evolution, Ohno (1970) pointed out that at least one of the two copies may become less constrained by selection and thus be able to evolve toward a new function. Hughes and Hughes (1993) tested this hypothesis in the recent tetraploid Xenopus laevis and showed that both Duplicate copies evolve at the same rate, with evidence of negative selection on both. Our aim was to characterize whether Duplicated Genes have allowed a further exploration of the adaptative landscape in teleost fish and mammalian genomes. For this, we compared all Genes for which at least one duplication was characterized either in a teleost fish or in a eutherian mammal. Although pseudoGenes are relevant to the overall duplication rate, they do not participate in an eventual adaptative role of gene or genome duplication. Since we were interested here in functional evolution, we did not take into account duplications which clearly led to the formation of pseudoGenes. This was done by the exclusion in the HOVERGEN database (Duret, Mouchiroud, and Gouy 1994) of all sequences explicitly declared to be pseudoGenes. For each of these Genes, we compared rates (1) between the two Duplicated copies, as in Hughes and Hughes (1993), and (2) between the lineage with the duplication and the lineage without the duplication. Indeed, if gene duplication is followed by a relaxation of selective constraint on Genes, the resulting copies should evolve faster than their orthologs in other species which were not Duplicated. The second test should be able to detect a decrease in selection on either or both copies, unlike the first. In practice, we build a 2 3 2 contingency table to compare the observed and expected numbers of Genes under the hypothesis of independence between the lineage with the duplication and the lineage with the highest substitution rate (mammals or teleost fish). Genes were recovered from the HOVERGEN database (Duret, Mouchiroud, and Gouy 1994), allowing
