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Joni M. Seeling - One of the best experts on this subject based on the ideXlab platform.
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A NonSynonymous/Synonymous Substitution Analysis of the B56 Gene Family Aids in Understanding B56 Isoform Diversity.
PloS one, 2015Co-Authors: Osama Qureshi, Hyuk Cho, Madhusudan Choudhary, Joni M. SeelingAbstract:Gene duplication leads to the formation of gene families, wherein purifying or neutral selection maintains the original gene function, while diversifying selection confers new functions onto duplicated genes. The B56 gene family is highly conserved; it is encoded by one gene in protists and fungi, and five genes in vertebrates. B56 regulates protein phosphatase 2A (PP2A), an abundant heterotrimeric serine/threonine phosphatase that functions as a tumor suppressor and consists of a scaffolding "A" and catalytic "C" subunit heterodimer bound to a regulatory "B" subunit. Individual regulatory B56 subunits confer disparate functions onto PP2A in various cell-cell signaling pathways. B56 proteins share a conserved central core domain, but have divergent N- and C-termini which play a role in isoform specificity. We carried out a nonSynonymous/Synonymous Substitution analysis to better understand the divergence of vertebrate B56 genes. When five B56 paralogs from ten vertebrate species were analyzed, the gene family displayed purifying selection; stronger purifying selection was revealed when individual B56 isoforms were analyzed separately. The B56 core experienced stronger purifying selection than the N- and C-termini, which correlates with the presence of several contacts between the core and the AC heterodimer. Indeed, the majority of the contact points that we analyzed between B56 and the AC heterodimer experienced strong purifying selection. B56 subfamilies showed distinct patterns of selection in their N- and C-termini. The C-terminus of the B56-1 subfamily and the N-terminus of the B56-2 subfamily exhibited strong purifying selection, suggesting that these termini carry out subfamily-specific functions, while the opposite termini exhibited diversifying selection and likely carry out isoform-specific functions. We also found reduced Synonymous Substitutions at the N- and C-termini when grouping B56 genes by species but not by isoform, suggesting species-specific codon bias may have a role in regulating B56 gene expression.
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a nonSynonymous Synonymous Substitution analysis of the b56 gene family aids in understanding b56 isoform diversity
PLOS ONE, 2015Co-Authors: Osama Qureshi, Hyuk Cho, Madhusudan Choudhary, Joni M. SeelingAbstract:Gene duplication leads to the formation of gene families, wherein purifying or neutral selection maintains the original gene function, while diversifying selection confers new functions onto duplicated genes. The B56 gene family is highly conserved; it is encoded by one gene in protists and fungi, and five genes in vertebrates. B56 regulates protein phosphatase 2A (PP2A), an abundant heterotrimeric serine/threonine phosphatase that functions as a tumor suppressor and consists of a scaffolding "A" and catalytic "C" subunit heterodimer bound to a regulatory "B" subunit. Individual regulatory B56 subunits confer disparate functions onto PP2A in various cell-cell signaling pathways. B56 proteins share a conserved central core domain, but have divergent N- and C-termini which play a role in isoform specificity. We carried out a nonSynonymous/Synonymous Substitution analysis to better understand the divergence of vertebrate B56 genes. When five B56 paralogs from ten vertebrate species were analyzed, the gene family displayed purifying selection; stronger purifying selection was revealed when individual B56 isoforms were analyzed separately. The B56 core experienced stronger purifying selection than the N- and C-termini, which correlates with the presence of several contacts between the core and the AC heterodimer. Indeed, the majority of the contact points that we analyzed between B56 and the AC heterodimer experienced strong purifying selection. B56 subfamilies showed distinct patterns of selection in their N- and C-termini. The C-terminus of the B56-1 subfamily and the N-terminus of the B56-2 subfamily exhibited strong purifying selection, suggesting that these termini carry out subfamily-specific functions, while the opposite termini exhibited diversifying selection and likely carry out isoform-specific functions. We also found reduced Synonymous Substitutions at the N- and C-termini when grouping B56 genes by species but not by isoform, suggesting species-specific codon bias may have a role in regulating B56 gene expression.
Adam Eyre-walker - One of the best experts on this subject based on the ideXlab platform.
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Partitioning the Variation in Mammalian Substitution Rates
Molecular biology and evolution, 2003Co-Authors: Nick G.c. Smith, Adam Eyre-walkerAbstract:We have used analysis of variance to partition the variation in Synonymous and amino acid Substitution rates between three effects (gene, lineage, and a gene-by-lineage interaction) in mammalian nuclear and mitochondrial genes. We find that gene effects are stronger for amino acid Substitution rates than for Synonymous Substitution rates and that lineage effects are stronger for Synonymous Substitution rates than for amino acid Substitution rates. Gene-by-lineage interactions, equivalent to overdispersion corrected for lineage effects, are found in amino acid Substitutions but not in Synonymous Substitutions. The variance in the ratio of amino acid and Synonymous Substitution rates is dominated by gene effects, but there is also a significant gene-by-lineage interaction.
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Correlated rates of Synonymous site evolution across plant genomes.
Molecular biology and evolution, 1997Co-Authors: Adam Eyre-walker, Brandon S. GautAbstract:Synonymous Substitution rates have been shown to vary among evolutionary lineages of both nuclear and organellar genes across a broad range of taxonomic groups. In animals, rate heterogeneity does not appear to be correlated across nuclear and mitochondrial genes. In this paper, we contrast Substitution rates in two plant groups and show that grasses evolve more rapidly than palms at Synonymous sites in a mitochondrial, a nuclear, and a plastid gene. Furthermore, we show that the relative rates of Synonymous Substitution between grasses and palms are similar at the three loci. The correlation in Synonymous Substitution rates across genes is particularly striking because the three genes evolve at very different absolute rates. In contrast, relative rates of nonSynonymous Substitution are not conserved among the three genes.
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Synonymous Substitution rates in enterobacteria.
Genetics, 1995Co-Authors: Adam Eyre-walker, Michael BulmerAbstract:It has been shown previously that the Synonymous Substitution rate between Escherichia coli and Salmonella typhimurium is lower in highly than in weakly expressed genes, and it has been suggested that this is due to stronger selection for translational efficiency in highly expressed genes as reflected in their greater codon usage bias. This hypothesis is tested here by comparing the Substitution rate in codon families with different patterns of Synonymous codon use. It is shown that the decline in the Substitution rate across expression levels is as great for codon families that do not appear to be subject to selection for translational efficiency as for those that are. This implies that selection on translational efficiency is not responsible for the decline in the Substitution rate across genes. It is argued that the most likely explanation for this decline is a decrease in the mutation rate. It is also shown that a simple evolutionary model in which Synonymous codon use is determined by a balance between mutation, selection for an optimal codon, and genetic drift predicts that selection should have little effect on the Substitution rate in the present case.
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Synonymous Substitutions Are Clustered in Enterobacterial Genes
Journal of molecular evolution, 1994Co-Authors: Adam Eyre-walkerAbstract:The spatial distribution of Synonymous Substitutions in enterobacterial genes is investigated. It is shown that Synonymous Substitutions are significantly clustered in such a way that a Synonymous Substitution in one codon elevates the rate of Synonymous Substitution in an adjacent codon by about 10%. The level of clustering does not appear to be related to the level of gene expression, and it is restricted to a range of two or three codons. There are at least three possible explanations: (1) sequence-directed mutagenesis, (2) recombination, and (3) selection.
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Reduced Synonymous Substitution rate at the start of enterobacterial genes.
Nucleic acids research, 1993Co-Authors: Adam Eyre-walker, Michael BulmerAbstract:It has been shown previously that the Synonymous Substitution rate between Escherichia coli and Salmonella typhimurium is lower in highly than in weakly expressed genes, and it has been suggested that this is due to stronger selection for translational efficiency in highly expressed genes as reflected in their greater codon usage bias. This hypothesis is tested here by comparing the Substitution rate in codon families with different patterns of Synonymous codon use. It is shown that the decline in the Substitution rate across expression levels is as great for codon families that do not appear to be subject to selection for translational efficiency as for those that are. This implies that selection on translational efficiency is not responsible for the decline in the Substitution rate across genes. It is argued that the most likely explanation for this decline is a decrease in the mutation rate. It is also shown that a simple evolutionary model in which Synonymous codon use is determined by a balance between mutation, selection for an optimal codon, and genetic drift predicts that selection should have little effect on the Substitution rate in the present case.
Osama Qureshi - One of the best experts on this subject based on the ideXlab platform.
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A NonSynonymous/Synonymous Substitution Analysis of the B56 Gene Family Aids in Understanding B56 Isoform Diversity.
PloS one, 2015Co-Authors: Osama Qureshi, Hyuk Cho, Madhusudan Choudhary, Joni M. SeelingAbstract:Gene duplication leads to the formation of gene families, wherein purifying or neutral selection maintains the original gene function, while diversifying selection confers new functions onto duplicated genes. The B56 gene family is highly conserved; it is encoded by one gene in protists and fungi, and five genes in vertebrates. B56 regulates protein phosphatase 2A (PP2A), an abundant heterotrimeric serine/threonine phosphatase that functions as a tumor suppressor and consists of a scaffolding "A" and catalytic "C" subunit heterodimer bound to a regulatory "B" subunit. Individual regulatory B56 subunits confer disparate functions onto PP2A in various cell-cell signaling pathways. B56 proteins share a conserved central core domain, but have divergent N- and C-termini which play a role in isoform specificity. We carried out a nonSynonymous/Synonymous Substitution analysis to better understand the divergence of vertebrate B56 genes. When five B56 paralogs from ten vertebrate species were analyzed, the gene family displayed purifying selection; stronger purifying selection was revealed when individual B56 isoforms were analyzed separately. The B56 core experienced stronger purifying selection than the N- and C-termini, which correlates with the presence of several contacts between the core and the AC heterodimer. Indeed, the majority of the contact points that we analyzed between B56 and the AC heterodimer experienced strong purifying selection. B56 subfamilies showed distinct patterns of selection in their N- and C-termini. The C-terminus of the B56-1 subfamily and the N-terminus of the B56-2 subfamily exhibited strong purifying selection, suggesting that these termini carry out subfamily-specific functions, while the opposite termini exhibited diversifying selection and likely carry out isoform-specific functions. We also found reduced Synonymous Substitutions at the N- and C-termini when grouping B56 genes by species but not by isoform, suggesting species-specific codon bias may have a role in regulating B56 gene expression.
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a nonSynonymous Synonymous Substitution analysis of the b56 gene family aids in understanding b56 isoform diversity
PLOS ONE, 2015Co-Authors: Osama Qureshi, Hyuk Cho, Madhusudan Choudhary, Joni M. SeelingAbstract:Gene duplication leads to the formation of gene families, wherein purifying or neutral selection maintains the original gene function, while diversifying selection confers new functions onto duplicated genes. The B56 gene family is highly conserved; it is encoded by one gene in protists and fungi, and five genes in vertebrates. B56 regulates protein phosphatase 2A (PP2A), an abundant heterotrimeric serine/threonine phosphatase that functions as a tumor suppressor and consists of a scaffolding "A" and catalytic "C" subunit heterodimer bound to a regulatory "B" subunit. Individual regulatory B56 subunits confer disparate functions onto PP2A in various cell-cell signaling pathways. B56 proteins share a conserved central core domain, but have divergent N- and C-termini which play a role in isoform specificity. We carried out a nonSynonymous/Synonymous Substitution analysis to better understand the divergence of vertebrate B56 genes. When five B56 paralogs from ten vertebrate species were analyzed, the gene family displayed purifying selection; stronger purifying selection was revealed when individual B56 isoforms were analyzed separately. The B56 core experienced stronger purifying selection than the N- and C-termini, which correlates with the presence of several contacts between the core and the AC heterodimer. Indeed, the majority of the contact points that we analyzed between B56 and the AC heterodimer experienced strong purifying selection. B56 subfamilies showed distinct patterns of selection in their N- and C-termini. The C-terminus of the B56-1 subfamily and the N-terminus of the B56-2 subfamily exhibited strong purifying selection, suggesting that these termini carry out subfamily-specific functions, while the opposite termini exhibited diversifying selection and likely carry out isoform-specific functions. We also found reduced Synonymous Substitutions at the N- and C-termini when grouping B56 genes by species but not by isoform, suggesting species-specific codon bias may have a role in regulating B56 gene expression.
Michael Bulmer - One of the best experts on this subject based on the ideXlab platform.
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Synonymous Substitution rates in enterobacteria.
Genetics, 1995Co-Authors: Adam Eyre-walker, Michael BulmerAbstract:It has been shown previously that the Synonymous Substitution rate between Escherichia coli and Salmonella typhimurium is lower in highly than in weakly expressed genes, and it has been suggested that this is due to stronger selection for translational efficiency in highly expressed genes as reflected in their greater codon usage bias. This hypothesis is tested here by comparing the Substitution rate in codon families with different patterns of Synonymous codon use. It is shown that the decline in the Substitution rate across expression levels is as great for codon families that do not appear to be subject to selection for translational efficiency as for those that are. This implies that selection on translational efficiency is not responsible for the decline in the Substitution rate across genes. It is argued that the most likely explanation for this decline is a decrease in the mutation rate. It is also shown that a simple evolutionary model in which Synonymous codon use is determined by a balance between mutation, selection for an optimal codon, and genetic drift predicts that selection should have little effect on the Substitution rate in the present case.
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Reduced Synonymous Substitution rate at the start of enterobacterial genes.
Nucleic acids research, 1993Co-Authors: Adam Eyre-walker, Michael BulmerAbstract:It has been shown previously that the Synonymous Substitution rate between Escherichia coli and Salmonella typhimurium is lower in highly than in weakly expressed genes, and it has been suggested that this is due to stronger selection for translational efficiency in highly expressed genes as reflected in their greater codon usage bias. This hypothesis is tested here by comparing the Substitution rate in codon families with different patterns of Synonymous codon use. It is shown that the decline in the Substitution rate across expression levels is as great for codon families that do not appear to be subject to selection for translational efficiency as for those that are. This implies that selection on translational efficiency is not responsible for the decline in the Substitution rate across genes. It is argued that the most likely explanation for this decline is a decrease in the mutation rate. It is also shown that a simple evolutionary model in which Synonymous codon use is determined by a balance between mutation, selection for an optimal codon, and genetic drift predicts that selection should have little effect on the Substitution rate in the present case.
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Synonymous nucleotide Substitution rates in mammalian genes implications for the molecular clock and the relationship of mammalian orders
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Michael Bulmer, Kenneth H. Wolfe, Paul M. SharpAbstract:Abstract Synonymous Substitution rates have been estimated for 58 genes compared among primates, artiodactyls, and rodents. Although silent sites might be expected to be neutral, there is substantial rate variation among genes within each lineage. Some of the rate variation is associated with G + C content: genes with intermediate G + C values have the highest rates. Nevertheless, considerable heterogeneity remains after correcting for G + C content. Synonymous Substitution rates also vary among lineages, but the relative rates of genes are well conserved in different lineages. Certain genes have also been sequenced in a fourth order (lagomorph or carnivore), and these data have been used to investigate mammalian phylogeny. Data on lagomorphs are consistent with a star phylogeny, but there is evidence that carnivores and artiodactyls are sister groups. Genes sequenced in both rat and mouse suggest that the increased Substitution rate in rodents has occurred since the rat/mouse divergence.
Yoko Satta - One of the best experts on this subject based on the ideXlab platform.
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Heterogeneity of Synonymous Substitution rates in the Xenopus frog genome.
PloS one, 2020Co-Authors: Quintin Lau, Takeshi Igawa, Hajime Ogino, Yukako Katsura, Toshimichi Ikemura, Yoko SattaAbstract:With the increasing availability of high quality genomic data, there is opportunity to deeply explore the genealogical relationships of different gene loci between closely related species. In this study, we utilized genomes of Xenopus laevis (XLA, a tetraploid species with (L) and (S) sub-genomes) and X. tropicalis (XTR, a diploid species) to investigate whether Synonymous Substitution rates among orthologous or homoeologous genes displayed any heterogeneity. From over 1500 orthologous/homoeologous genes collected, we calculated proportion of Synonymous Substitutions between genomes/sub-genomes (k) and found variation within and between chromosomes. Within most chromosomes, we identified higher k with distance from the centromere, likely attributed to higher Substitution rates and recombination in these regions. Using maximum likelihood methods, we identified further evidence supporting rate heterogeneity, and estimated species divergence times and ancestral population sizes. Estimated species divergence times (XLA.L-XLA.S: ~25.5 mya; XLA-XTR: ~33.0 mya) were slightly younger compared to a past study, attributed to consideration of population size in our study. Meanwhile, we found very large estimated population size in the ancestral populations of the two species (NA = 2.55 x 106). Local hybridization and population structure, which have not yet been well elucidated in frogs, may be a contributing factor to these possible large population sizes.
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Natural selection in the TLR-related genes in the course of primate evolution
Immunogenetics, 2008Co-Authors: Toshiaki Nakajima, Yoko Satta, Hitoshi Ohtani, Hirofumi Akari, Takafumi Ishida, Akinori KimuraAbstract:The innate immune system constitutes the front line of host defense against pathogens. Toll-like receptors (TLRs) recognize molecules derived from pathogens and play crucial roles in the innate immune system. Here, we provide evidence that the TLR-related genes have come under natural selection pressure in the course of primate evolution. We compared the nucleotide sequences of 16 TLR-related genes, including TLR s ( TLR1–10 ), MYD88 , TILAP , TICAM1 , TICAM2 , MD2 , and CD14 , among seven primate species. Analysis of the non-Synonymous/Synonymous Substitution ratio revealed the presence of both strictly conserved and rapidly evolving regions in the TLR-related genes. The genomic segments encoding the intracellular Toll/interleukin 1 receptor domains, which exhibited lower rates of non-Synonymous Substitution, have undergone purifying selection. In contrast, TLR4 , which carried a high proportion of non-Synonymous Substitutions in the part of extracellular domain spanning 200 amino acids, was found to have been the suggestive target of positive Darwinian selection in primate evolution. However, sequence analyses from 25 primate species, including eight hominoids, six Old World monkeys, eight New World monkeys, and three prosimians, showed no evidence that the pressure of positive Darwinian selection has shaped the pattern of sequence variations in TLR4 among New World monkeys and prosimians.
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Mhc-DRB genes evolution in lemurs.
Immunogenetics, 2002Co-Authors: Yasuhiro Go, Yoko Satta, Yoshi Kawamoto, Gilbert Rakotoarisoa, Albert Randrianjafy, Naoki Koyama, Hirohisa HiraiAbstract:Partial exon 2 sequences (202 bp) of the lemur Mhc-DRB genes were sequenced. A total of 137 novel sequences were detected in 66 lemurs, representing four out of the five extant families. Trans-species polymorphisms and even identical sequences were observed not only among genera but also among families. Based on the time-scale of lemur evolution, these findings suggest that some identical sequences have been maintained for more than 40 million years. This is in contrast to the evolutionary mode of simian DRB genes, where such identical sequences have been retained for at most several million years. To explore the reasons behind these unexpected findings, the degree of recombination and the Synonymous Substitution rate in lemurs and simians were examined. We found that (1) little difference existed in the extent of recombination, (2) frequent recombination occurred within the α-helix as well as between the β-pleated sheet and the α-helix, and (3) the Synonymous Substitution rate was significantly reduced in lemur lineages. Upon phylogenetic analysis, lemur DRB genes were clustered by themselves and separated from the other primate DRB genes (simians and non-Malagasy prosimians). This result suggests that the DRB variations in extant lemur populations have been generated after the divergence of the lemurs from the remaining primates. This mode of Substitution accumulation is also supported by a pattern of mismatch distribution among lemur DRB genes. These observations correspond with the postulation that a severe bottleneck occurred when the ancestors of lemurs settled into Madagascar from the African continent.
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The Synonymous Substitution rate of the major histocompatibility complex loci in primates
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Yoko Satta, Colm O'huigin, Naoyuki Takahata, Jan KleinAbstract:Abstract Because the divergence of many allelic lineages at the major histocompatibility complex (MHC) loci predates species divergence, standard methods of calculating Synonymous Substitution rates are not applicable to this system. We used three alternative methods of rate estimation: one based on the minimum number of Substitutions (Dm), another on the nucleotide difference (Dxy), and the third on the net nucleotide difference (Dn). We applied these methods to the protein-encoding sequences of primate MHC class I (A, B, and C) and class II (DRB1) genes. To determine the reliability of the different estimates, we carried out computer simulation. The distribution of the estimates based on Dxy or Dn is generally much broader than that based on Dm. More importantly, the Dm-based method nearly always has the highest probability of recovering true rates, provided that Dm is not smaller than 5. Because of its desirable statistical properties, we used the Dm-based method to estimate the rate of Synonymous Substitutions. The rate is 1.37 +/- 0.61 for A, 1.84 +/- 0.40 for B, 3.87 +/- 1.05 for C, and 1.18 +/- 0.36 for DRB1 loci, always per site per 10(9) years. Hence despite the extraordinary polymorphism, the mutation rate at the primate MHC loci is no higher than that of other loci.
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Evolution of hominoid mitochondrial DNA with special reference to the silent Substitution rate over the genome.
Journal of molecular evolution, 1993Co-Authors: Rumi Kondo, Yoko Satta, Satoshi Horai, Naoyuki TakahataAbstract:Focusing on the Synonymous Substitution rate, we carried out detailed sequence analyses of hominoid mitochondrial (mt) DNAs of ca. 5-kb length. Owing to the outnumbered transitions and strong biases in the base compositions, Synonymous Substitutions in mtDNA reach rapidly a rather low saturation level. The extent of the compositional biases differs from gene to gene. Such changes in base compositions, even if small, can bring about considerable variation in observed Synonymous differences and may result in the region-dependent estimate of the Synonymous Substitution rate. We demonstrate that such a region dependency is due to a failure to take proper account of heterogeneous compositional biases from gene to gene but that the actual Synonymous Substitution rate is rather uniform. The Synonymous Substitution rate thus estimated is 2.37 ± 0.11 × 10−8 per site per year and comparable to the overall rate for the noncoding region. On the other hand, the rate of nonSynonymous Substitutions differs considerably from gene to gene, as expected under the neutral theory of molecular evolution. The lowest rate is 0.8 × 10−9 per site per year forCOI and the highest rate is 4.5 × 10−9 forATPase 8, the degree of functional constraints (measured by the ratio of the nonSynonymous to the Synonymous Substitution rate) being 0.03 and 0.19, respectively. Transfer RNA (tRNA) genes also show variability in the base contents and thus in the nucleotide differences. The average rate for 11 tRNAs contained in the 5-kb region is 3.9 × 10−9 per site per year. The nucleotide Substitutions in the genome suggest that the transition rate is about 17 times faster than the transversion rate.
