SEARCH · Search PubMed

Results for “synonymous mutation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources

PubMed1998

Identification of a naturally occurring Pro15-Ser15 substitution in the serotonin5A receptor gene in alcoholics and healthy volunteers.

We screened the serotonin5A receptor gene coding region in 186 unrelated alcoholic patients and 187 controls. A relatively abundant amino acid substitution and two synonymous DNA substitutions were detected. Two synonymous variants, A12T and C789T, had rarer-allele frequencies of 23% and 1%, respectively. The Pro15Ser substitution is located in the amino terminal, extracellular domain of the receptor adjacent to a putative phosphorylation site. Pro15Ser had rarer-allele frequencies of 8.1% and 5.9% in Finnish alcoholic patients and controls, respectively (p=n.s.).

Alcoholism↗

PubMed2005

Identification of four novel HLA-DOA alleles, DOA010106, DOA0102, DOA0103, and DOA0104N, by sequence-based typing*.

DOA sequences are currently known to have identical protein sequences. However, in this study, we report four novel allele types of human leucocyte antigen-DOA, including one synonymous and three non- synonymous amino acid changes from the Korean population. DOA*010106 has identical protein sequence with previously known DOA*010103 except one nucleotide difference at codon 45 (TCG-->TCA). In contrast, DOA*0102 and DOA*0103 have a sequence change at codon 99 (CTG-->GTG) and codon 105 (CGC-->TGC), causing non-synonymous amino acid changes, Leu99Val and Arg105Cys, respectively. In addition, DOA*0104N has a sequence deletion at codon 36 (CCC-->CC-), resulting in a frame shift leading to a stop codon at codon 62.

Alleles↗

PubMed2004

Mitochondrial DNA nucleotide changes in non-arteritic ischemic optic neuropathy.

The authors sequenced the entire mitochondrial DNA coding region in a group of 19 patients with non-arteritic anterior ischemic optic neuropathy (NAION) and in 100 controls. Synonymous and nonsynonymous nucleotide changes were more common in NAION patients (p < 0.001). Twelve of these (11 novel) were potentially pathologic, nine of which altered moderately or highly conserved amino acids in the functional domain of the affected protein. Mitochondrial malfunction may be a risk factor for NAION.

Adult↗

PubMed2003

Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster.

One objective of quantitative genetics is to identify the nucleotide variants within genes that contribute to phenotypic variation and susceptibility [1]. In an evolutionary context, this means characterizing the molecular polymorphisms that modify the penetrance and expressivity of perturbed traits. A survey of association between 267 SNPs in almost 11 kb of the D. melanogaster Egfr and the degree of eye roughening due to a gain-of-function Egfr(E1) allele crossed into 210 isogenic wild-type lines provides evidence that a handful of synonymous substitutions supply cryptic variation for photoreceptor determination. Ten sites exceed Bonferroni threshold for association in two sets of crosses to different Egfr(E1) backgrounds including a particularly significant cluster of sites in tight linkage disequilibrium toward the 3' end of the coding region. Epistatic interaction of this cluster with one other site enhances the expressivity of this haplotype. Replication of the strongest associations with an independent sample of 302 phenotypically extreme individuals derived from 1000 crosses of Egfr(E1) to freshly trapped males was achieved using modified case-control and transmission-disequilibrium tests. A tendency for the rarer alleles to have more disrupted eye development suggests that mutation-selection balance is a possible mechanism contributing to maintaining cryptic variation for Egfr.

Alleles↗

PubMed2005

The genes encoding for D4Z4 binding proteins HMGB2, YY1, NCL, and MYOD1 are excluded as candidate genes for FSHD1B.

Facioscapulohumeral muscular dystrophy is a disease of skeletal muscle, with symptoms including both facial and shoulder girdle weakness and progression to involve the pelvic girdle and extremities in the majority of cases. For most cases of FSHD, the molecular basis of the disease can be identified as a partial deletion of the D4Z4 repeat array on the end of the long arm of chromosome 4. However, in up to 5% of FSHD families there is no linkage to 4q35. These cases are designated as FSHD1B. Proteins have been identified that bind to the D4Z4 repeats of chromosome 4q35. The genes encoding D4Z4 binding proteins YY1, HMGB2, NCL, and MYOD1 were investigated as candidate genes for FSHD1B. Coding sequences and promoter region were analyzed for HMBG2 and no sequence variations were detected. For YY1, all five exons were analyzed and a polymorphism was detected in both the unaffected and affected populations. In nucleolin (NCL), several SNPs were identified, including a SNP causing the non-synonymous change P515H; however, all polymorphisms either occurred in control samples or were previously reported. A novel polymorphism was also detected in MYOD1, but did not represent a disease-specific variation. These results suggest that HMBG2, YY1, NCL, and MYOD1 are unlikely to represent the genes responsible for FSHD in these families.

Chromatography, High Pressure Liquid↗

PubMed2002

Polymorphisms of chromogranin B gene associated with schizophrenia in Chinese Han population.

Chromogranin is a widespread family of proteins in the neurosystem, whose function is guiding the sorting and secretion of neuropeptides. Using functional and positional evidences, chromogranin B was selected as a candidate gene for schizophrenia. We systematically screened all the promoter and exon regions of the gene and detected 15 single nucleotide polymorphisms (SNPs), among which four SNPs (including two non-synonymous SNPs) were selected for association analysis. In a cohort of Chinese Han schizophrenia cases and controls, the results of both the individual SNPs and the haplotypes of SNPs were significantly positive (P<0.01). Our results confirm the role of neuropeptides in the pathogenesis of schizophrenia.

Adult↗

PubMed2002

Extremely low levels of genetic polymorphism in endosymbionts (Buchnera) of aphids (Pemphigus).

Molecular evolutionary studies have suggested that vertically transmitted endosymbionts are subject to accumulation of deleterious mutations through genetic drift. Predictions of this hypothesis for patterns of intraspecific polymorphism were borne out in the single relevant study available, on the symbiont Buchnera aphidicola of Uroleucon ambrosiae. In order to examine the generality of this result, we surveyed DNA sequence variation in Buchnera of the distantly related aphid, Pemphigus obesinymphae. In contrast to Uroleucon species, Pemphigus species have complex life cycles with few dispersal stages. Despite these differences, P. obesinymphae showed patterns of variation at two Buchnera loci and one mitochondrial locus that were remarkably similar to those reported previously for Buchnera of U. ambrosiae. In the western US, Buchnera was nearly monomorphic, and in the eastern US, synonymous divergence ranged from 0.08 to 0.16%. Most polymorphisms involved rare alleles, consistent with a recent range of ancestral polymorphism, probably due to demographic fluctuations in aphid populations. These results support the generality of small effective population size in Buchnera and their aphid hosts.

Animals↗

PubMed1989

Some aspects of the organization and evolution of the genetic code.

In this paper, I define a measure of the relative position of each amino acid in the genetic code by means of a 21-dimensional vector describing its potential for mutation, in a single step, to each of the other amino acids, or to a chain termination codon. This measure allows us to make a systematic investigation of the type and number of the physicochemical properties of the amino acids that were involved in evolution. The polar character and size of amino acids are identified in this analysis as properties that played a leading role in the evolutionary history of the genetic code. The application of cluster analysis and discriminant analysis reveals the characteristics of the structural organization of the genetic code. Finally, I suggest the existence of a relationship between the molecular weight of the amino acids and the number of synonymous codons.

Amino Acids↗

PubMed2006

Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box binding protein gene: an evolutionary approach.

The variability and mutational changes of the CAG microsatellite in the TATA-box binding protein gene (TBP) were studied. We sequenced the microsatellite of the TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and 15 unaffected control individuals). In addition, the microsatellites were sequenced from individuals of 10 northern German families with at least one family member affected by SCA17. To study also the evolutionary history of this CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar, Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta, Papio hamadryas, Colobus polykomos and Callithrix jacchus. Three major conclusions were drawn: (i) Patterns of synonymous CAA interruptions in the microsatellite are characteristic and likely to result from selection for stabilizing the repetitive region; (ii) Interspecific comparisons indicate that SCA17 is likely to be a human trait. The most common allele in humans (37 repeats) is close to the threshold value upon which neurodegenerative changes can occur and may act as a repository for expanded, pathogenic alleles; (iii) The cassette-like structure of five out of 17 expanded alleles can be attributed to unequal crossing over. This can explain the rare and sporadic de novo generation of SCA17 alleles.

Animals↗

PubMed2001

Low rates of silent substitution in nuclear genes of two distantly related Scrophulariaceae (Antirrhinum and Verbascum).

Low levels of genetic diversity and divergence at nuclear loci have previously been observed for cycloidea and fil1-like genes within and between several Antirrhinum species, and divergence at these loci is also low between species in genera at different levels of relatedness in the former family Scrophulariaceae (Digitalis and Verbascum). The low divergence values are surprising, because (based on the sequences of chloroplast loci) the Scrophulariaceae are thought to be polyphyletic, with two anciently diverged clades, and the species we compared belonged to the two different clades. Here, we extend our studies of sequence divergence to more nuclear genes: fil2, far, globosa, and ADH: Detailed studies revealed that in Antirrhinum these genes belong to gene families. Low levels of divergence between Antirrhinum and Verbascum were observed for four of the loci studied, fil2-1, fil2-2, far-L, and globosa, similar to our previous observations. We discuss hypotheses to explain these low synonymous divergence values. For Adh, no cases of very similar sequences were found, but, rather, our sequences from the three different genera (Antirrhinum, Digitalis, and Verbascum) were all very diverged. Repeated gene duplication and loss of elements in the Adh gene family is likely in these lineages, making it impossible to determine orthology of the Adh genes.

Cell Nucleus↗

PubMed2002

Patterns of nucleotide substitution among simultaneously duplicated gene pairs in Arabidopsis thaliana.

We characterized rates and patterns of synonymous and nonsynonymous substitution in 242 duplicated gene pairs on chromosomes 2 and 4 of Arabidopsis thaliana. Based on their collinear order along the two chromosomes, the gene pairs were likely duplicated contemporaneously, and therefore comparison of genetic distances among gene pairs provides insights into the distribution of nucleotide substitution rates among plant nuclear genes. Rates of synonymous substitution varied 13.8-fold among the duplicated gene pairs, but 90% of gene pairs differed by less than 2.6-fold. Average nonsynonymous rates were approximately fivefold lower than average synonymous rates; this rate difference is lower than that of previously studied nonplant lineages. The coefficient of variation of rates among genes was 0.65 for nonsynonymous rates and 0.44 for synonymous rates, indicating that synonymous and nonsynonymous rates vary among genes to roughly the same extent. The causes underlying rate variation were explored. Our analyses tentatively suggest an effect of physical location on synonymous substitution rates but no similar effect on nonsynonymous rates. Nonsynonymous substitution rates were negatively correlated with GC content at synonymous third codon positions, and synonymous substitution rates were negatively correlated with codon bias, as observed in other systems. Finally, the 242 gene pairs permitted investigation of the processes underlying divergence between paralogs. We found no evidence of positive selection, little evidence that paralogs evolve at different rates, and no evidence of differential codon usage or third position GC content.

Arabidopsis↗

PubMed1993

Silent substitutions in mammalian genomes and their evolutionary implications.

An analysis of silent substitutions in pairwise comparisons of homologous genes from different mammals has shown that, in spite of individual fluctuations, their frequencies (which are very strongly correlated with the frequency of substitutions per synonymous site calculated according to Li et al. 1985) do not vary, on the average, with the GC levels of silent positions. This holds in the general case, in which silent positions of pairs of homologous genes share the same composition, namely in the human/other primates, human/artiodactyls, and in the mouse/rat pairs, as well as in the special cases in which the composition of silent positions are different, namely in the human/rabbit and the human/rat (or human/mouse) pairs. A slightly lower frequency found for low GC values in the human/bovine and human/pig pairs seems to be due to the specific gene samples used. These results contradict the previously claimed existence of differences in mutation rates and of mutational biases in third codon positions of coding sequences located in different isochores of mammalian genomes. They also imply that the variations in nucleotide precursor pools through the cell cycle and the differences in replication timing, or in repair efficiency, which were reported for different isochores, do not lead, as claimed, to differences in mutation rates, not in mutational biases in mammals. The differences claimed appear to be due to using small gene samples when individual fluctuations from gene to gene are relatively large.

Animals↗

PubMed1997

Accelerated evolution of sites undergoing mRNA editing in plant mitochondria and chloroplasts.

The selective constraints influencing mRNA editing in plant organelles are largely unknown. To investigate these, we compared patterns of editing between monocot and dicot mitochondrial mRNA. On average, 24% of sites that are edited form C to U in one species have been substituted during evolution by a genomic T in the other: this is four times the rate of evolution seen at nonedited synonymously variable C residues. A similar, but weaker trend (not statistically significant) is seen at sites edited in chloroplast mRNA. The elevated substitution rate does not appear to be a consequence of a higher mutability of the trinucleotide motif (T-C-purine) associated with editing. nor to be a result of reverse transcription from mature mRNA. Selection to replace the genomic C with a T may account for the accelerated evolution, either due to elimination of inefficient transcripts and protein products or as a consequence of the prior loss of components outside the edit site which are necessary for editing; the latter hypothesis is supported by the frequent loss of editing without genomic mutation at third codon positions. Whatever the cause, the rapid rate of evolution indicates that editing confers little selective advantage at most sites.

Base Sequence↗

PubMed2006

Retroposed elements as archives for the evolutionary history of placental mammals.

Reconstruction of the placental mammalian (eutherian) evolutionary tree has undergone diverse revisions, and numerous aspects remain hotly debated. Initial hierarchical divisions based on morphology contained many misgroupings due to features that evolved independently by similar selection processes. Molecular analyses corrected many of these misgroupings and the superordinal hierarchy of placental mammals was recently assembled into four clades. However, long or rapid evolutionary periods, as well as directional mutation pressure, can produce molecular homoplasies, similar characteristics lacking common ancestors. Retroposed elements, by contrast, integrate randomly into genomes with negligible probabilities of the same element integrating independently into orthologous positions in different species. Thus, presence/absence analyses of these elements are a superior strategy for molecular systematics. By computationally scanning more than 160,000 chromosomal loci and judiciously selecting from only phylogenetically informative retroposons for experimental high-throughput PCR applications, we recovered 28 clear, independent monophyly markers that conclusively verify the earliest divergences in placental mammalian evolution. Using tests that take into account ancestral polymorphisms, multiple long interspersed elements and long terminal repeat element insertions provide highly significant evidence for the monophyletic clades Boreotheria (synonymous with Boreoeutheria), Supraprimates (synonymous with Euarchontoglires), and Laurasiatheria. More importantly, two retropositions provide new support for a prior scenario of early mammalian evolution that places the basal placental divergence between Xenarthra and Epitheria, the latter comprising all remaining placentals. Due to its virtually homoplasy-free nature, the analysis of retroposon presence/absence patterns avoids the pitfalls of other molecular methodologies and provides a rapid, unequivocal means for revealing the evolutionary history of organisms.

Animals↗

PubMed2005

Identification of HLA-A*0111N: a synonymous substitution, introducing an alternative splice site in exon 3, silenced the expression of an HLA-A allele.

A new variant of the HLA-A*010101 allele designated as HLA-A*0111N, previously known as HLA-A*010101var, was identified in a patient requiring a stem-cell transplantation. The patient was typed by serologic methods as HLA-A2 homozygous and by sequence-based typing (SBT) as A*010101,020601. Flow-cytometric (FCM) analysis with 11 human monoclonal antibodies (mAbs) for the A1 molecule confirmed lack of any cell membrane expression of the A*0111N allele. One-dimensional isoelectric focusing (1D-IEF) of total cell lysate from the patient's cells revealed no cell surface and cytoplasmic A1 protein expression, whereas the HLA-A2 molecule was identified by both FCM analysis and 1D-IEF. DNA sequence analysis showed the presence of a synonymous substitution from G to T at position 597 in codon 175. RNA SBT revealed a deletion of 24 bp in exon 3, position 596 through 619, encoding codons 175 through 182 of the HLA-A*0111N allele. The synonymous substitution introduced a new splice site, resulting in an efficient splicing, because no classical A1 protein could be detected in the patient. This alternative splicing prevented the translation into a correct and stable class I molecule expression on the cell surface.

Alleles↗

PubMed2004

Molecular analysis of adenovirus isolates from vaccinated and unvaccinated young adults.

Infections of adenovirus type 4 (Ad4) and Ad7 were discovered among previously vaccinated individuals through febrile respiratory illness surveillance at military recruit camps. Genetic analysis was performed on these isolates and a sample of adenovirus isolates from unvaccinated patients. Antigenic regions of the adenovirus hexon gene from 21 vaccinated and 31 unvaccinated patients were sequenced and compared to homologous regions of Ad4 and Ad7 vaccine strains and of other representative hexon sequences archived in GenBank. The phylogenetic distribution of sequences from vaccinated individuals closely resembled those from unvaccinated individuals. The most common Ad7 strain was the Ad7d2 hexon genotype, and the most common Ad4 strain was a genotype nearly identical to the recently discovered Z-G 95-873 Ad4 variant. Near exclusive isolation of Ad4 since 1999 indicates that the Ad4 variant is currently responsible for the vast majority of adenovirus morbidity in military recruit camps. Different ratios of nonsynonymous to synonymous nucleotide substitution rates in known antigenic regions compared to nonantigenic regions indicated positive selection for diversity in the antigenic regions and purifying selection in the nonantigenic regions.

Adenovirus Infections, Human↗

PubMed1998

High sequence similarity within ras exons 1 and 2 in different mammalian species and phylogenetic divergence of the ras gene family.

We have determined the canine and feline N-, K-, and H-ras gene sequences from position +23 to +270 covering exons I and II which contain the mutational hot spot codons 12, 13, and 61. The results were used to assess the degree of similarity between ras gene DNA regions containing the critical domains affected in neoplastic disorders in different mammalian species. The comparative analyses performed included human, canine, feline, murine, rattine, and, whenever possible, bovine, leporine (rabbit), porcelline (guinea pig), and mesocricetine (hamster) ras gene sequences within the region of interest. Comparison of feline and canine nucleotide sequences with the corresponding regions in human DNA revealed a sequence similarity greater than 85% to the human sequence. Contemporaneous analysis of previously published ras DNA sequences from other mammalian species showed a similar degree of homology to human DNA. Most nucleotide differences observed represented synonymous changes without effect on the amino acid sequence of the respective proteins. For assessment of the phylogenetic evolution of ras gene family, a maximum parsimony dendrogram based on multiple sequence alignment of the common region of exons I and II in the N-, K-, and H-ras genes was constructed. Interestingly, a higher substitution rate among the H-ras genes became apparent, indicating accelerated sequence evolution within this particular clade. The most parsimonious tree clearly shows that the duplications giving rise to the three ras genes must have occurred before the mammalian radiation.

Animals↗

PubMed2001

Genetic variability, molecular evolution, and geographic diversity of HLA-B27.

HLA-B27 represents a family of 23 closely related alleles (B*2701-23) that differ at 24 amino acid positions. The pattern of polymorphisms of B27 was studied, with special reference to synonymous (Ks) and nonsynonymous (Ka) divergence among alleles. B27 alleles are characterized by the enhanced rate of nonsynonymous nucleotide substitution in the peptide-binding region (PBR). The percentage of substitutions between each of the B27 pairs ranges from 0.2%-3% in exons 2-3 to 1.8%-20.1% in the PBR. A phylogenetic analysis of all B27 alleles is described in order to identify subtypes with a common evolutionary history. These results, together with the phylogenetic trees obtained from the comparison between exons 2-3 and PBR indicate that polymorphism of B27 is selectively maintained. Most of the differences are clustered in the C/F pocket affecting the specific binding of antigenic peptides. Gene conversion and point mutation are the most important mechanisms responsible for B27 diversification. The interaction of selection, genetic drift, and recombination events is important for generating polymorphism at B27 alleles. We analyzed a large extended B27 positive population from different parts of the world. Our results indicate that B27 subtypes differ in their ethnic distribution, which may be the result of different genetic and geographical origins. Different factors such as genetic drift, bottleneck effect, and admixture among populations could contribute to the genetic constitution of B27. The striking correlation between the structural features of B27 and the ethnic distribution of these subtypes suggests a model of strong directional evolution, in which the subtypes could have arisen from B*2705.

Africa↗