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1
Stenger, Drake C., Brock A. Young, and Roy French. "Random mutagenesis of wheat streak mosaic virus HC-Pro: non-infectious interfering mutations in a gene dispensable for systemic infection of plants." Journal of General Virology 87, no. 9 (September 1, 2006): 2741–47. http://dx.doi.org/10.1099/vir.0.81933-0.
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Mutations within the HC-Pro coding region of Wheat streak mosaic virus (WSMV) were introduced by misincorporation during PCR and evaluated for phenotype within the context of an infectious clone. Nine synonymous substitutions and 15 of 25 non-synonymous substitutions had no phenotypic effect. Four non-synonymous substitutions, including one that reverted consistently to wild type, resulted in attenuated systemic infection. Six non-synonymous substitutions and one nonsense substitution abolished systemic infectivity. Mutants bearing the GUS reporter gene were evaluated for the ability to establish primary infection foci. All attenuated mutants and two systemic infection-deficient mutants produced localized regions of GUS expression on inoculated leaves 3 days post-inoculation. In vitro assays revealed that mutants able to establish infection foci retained HC-Pro proteinase activity. Among mutants unable to establish infection foci, HC-Pro proteinase activity was retained, reduced or absent. As a complete HC-Pro deletion mutant can infect plants systemically, certain substitutions in this dispensable gene probably prevented infection of WSMV via interference.
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Socha, W., J. Rola, and J. F. Żmudziński. "Variability of non-structural proteins of equine arteritis virus during persistent infection of the stallion." Polish Journal of Veterinary Sciences 18, no. 2 (June 1, 2015): 255–59. http://dx.doi.org/10.1515/pjvs-2015-0033.
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AbstractThe genetic stability of ORF1a encoding non-structural proteins nsp1, nsp2, nsp3 and nsp4 of equine arteritis virus (EAV) has been analysed for nearly seven years in a persistently infected stallion of the Malopolska breed. Between November 2004 and June 2011, 11 semen samples were collected. Viral RNA extracted from semen of this carrier stallion was amplified, sequenced and compared with the sequences of the other known strains of EAV. Sequence analysis of ORF1a showed 84 synonymous and 16 non-synonymous mutations. The most variable part of ORF1a was the region encoding nsp2 protein with 13 non-synonymous substitutions. The degree of amino acid identity between isolates ranged from 98.91 to 100%. Only single non-synonymous mutations were detected in nsp1 (one substitution) and nsp4 (two substitutions). The most stable was nsp3 in which no amino acid substitutions were observed during the whole period of observation.
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dos Reis, Mario. "How to calculate the non-synonymous to synonymous rate ratio of protein-coding genes under the Fisher–Wright mutation–selection framework." Biology Letters 11, no. 4 (April 2015): 20141031. http://dx.doi.org/10.1098/rsbl.2014.1031.
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First principles of population genetics are used to obtain formulae relating the non-synonymous to synonymous substitution rate ratio to the selection coefficients acting at codon sites in protein-coding genes. Two theoretical cases are discussed and two examples from real data (a chloroplast gene and a virus polymerase) are given. The formulae give much insight into the dynamics of non-synonymous substitutions and may inform the development of methods to detect adaptive evolution.
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Woolfit, Megan. "Effective population size and the rate and pattern of nucleotide substitutions." Biology Letters 5, no. 3 (April 8, 2009): 417–20. http://dx.doi.org/10.1098/rsbl.2009.0155.
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Both the overall rate of nucleotide substitution and the relative proportions of synonymous and non-synonymous substitutions are predicted to vary between species that differ in effective population size ( N e ). Our understanding of the genetic processes underlying these lineage-specific differences in molecular evolution is still developing. Empirical analyses indicate that variation in substitution rates and patterns caused by differences in N e is often substantial, however, and must be accounted for in analyses of molecular evolution.
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Llopart, Ana, and Montserrat Aguadé. "Synonymous Rates at the RpII215 Gene of Drosophila: Variation Among Species and Across the Coding Region." Genetics 152, no. 1 (May 1, 1999): 269–80. http://dx.doi.org/10.1093/genetics/152.1.269.
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Abstract The region encompassing the RpII215 gene that encodes the largest component of the RNA polymerase II complex (1889 amino acids) has been sequenced in Drosophila subobscura, D. madeirensis, D. guanche, and D. pseudoobscura. Nonsynonymous divergence estimates (Ka) indicate that this gene has a very low rate of amino acid replacements. Given its low Ka and constitutive expression, synonymous substitution rates are, however, unexpectedly high. Sequence comparisons have allowed the molecular clock hypothesis to be tested. D. guanche is an insular species and it is therefore expected to have a reduced effective size relative to D. subobscura. The significantly higher rate of synonymous substitutions detected in the D. guanche lineage could be explained if synonymous mutations behave as nearly neutral. Significant departure from the molecular clock hypothesis for synonymous and nonsynonymous substitutions was detected when comparing the D. subobscura, D. pseudoobscura, and D. melanogaster lineages. Codon bias and synonymous divergence between D. subobscura and D. melanogaster were negatively correlated across the RpII215 coding region, which indicates that selection coefficients for synonymous mutations vary across the gene. The C-terminal domain (CTD) of the RpII215 protein is structurally and functionally differentiated from the rest of the protein. Synonymous substitution rates were significantly different in both regions, which strongly indicates that synonymous mutations in the CTD and in the non-CTD regions are under detectably different selection coefficients.
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Kils-Hütten, Laurens, Rémi Cheynier, Simon Wain-Hobson, and Andreas Meyerhans. "Phylogenetic reconstruction of intrapatient evolution of human immunodeficiency virus type 1: predominance of drift and purifying selection." Journal of General Virology 82, no. 7 (July 1, 2001): 1621–27. http://dx.doi.org/10.1099/0022-1317-82-7-1621.
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The intra-host evolution of 73 human immunodeficiency virus type 1 quasispecies was analysed by split decomposition analysis. Non-synonymous and synonymous nucleotide substitutions were counted along the shortest path connecting all sequences and compared with the numbers expected under the assumption of a random model of mutation. For the majority of substitutions, drift and negative selection seemed to prevail.
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Belinky, Frida, Ishan Ganguly, Eugenia Poliakov, Vyacheslav Yurchenko, and Igor B. Rogozin. "Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events." International Journal of Molecular Sciences 22, no. 4 (February 14, 2021): 1876. http://dx.doi.org/10.3390/ijms22041876.
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Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels.
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Lehad, Arezki, Ilhem Selmi, Meriem Louanchi, Mouni Aitouada, and Naima Mahfoudhi. "Survey and Genetic Diversity of Grapevine Leafroll Associated Virus 2 in Algeria." International Journal of Phytopathology 4, no. 1 (May 2, 2015): 35–42. http://dx.doi.org/10.33687/phytopath.004.01.1074.
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Vineyards in western and center regions of Algeria were surveyed for the Grapevine leafroll-associated virus 2 (GLRaV-2). Analyses by DAS-ELISA and Reverse Transcription Polymerase Chain Reaction (RT-PCR) reveal 15, 8% prevalence. The genetic diversity of the GLRaV-2 population was studied by phylogenetic analyses of the HSP70h gene region of seven samples sequenced in this study and other sequences downloaded from GenBank. Results reveal segregation of the GLRav-2 population into six distinct groups. An estimation of the ratio of non-synonymous substitutions per non-synonymous site to synonymous substitutions per synonymous site indicated that HSP70h gene evolve under positive selection. Similarity plot constructed with representative sequence from each group confirmed previous results. All Algerian isolates belong to group PN. As far as we know, this is the first characterization of GLRaV-2 isolates from Algeria.
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Yakubu, Abdulmojeed, Adebowale Salako, Donato de, and Ikhide Imumorin. "Application of computational algorithms to assess the functionality of non-synonymous substitutions in MHC DRB gene of Nigerian goats." Genetika 49, no. 1 (2017): 63–76. http://dx.doi.org/10.2298/gensr1701063y.
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The Major Histocompatibility Complex (MHC) contains highly variable multi-gene families, which play a key role in the adaptive immune response within vertebrates. Among the Capra MHC class II genes, the expressed DRB locus is highly polymorphic, particularly in exon 2, which encodes the antigen-binding site. Models of variable non-synonymous/synonymous rate ratios among sites may provide important insights into functional constraints at different amino acid sites and may be used to detect sites under positive selection. Many non-synonymous single nucleotide polymorphisms (nsSNPs) at the DRB locus in goats are suspected to impact protein function. This study, therefore, aimed at comparing the efficiency of six computational approaches to predict the likelihood of a particular non-synonymous (amino acid change) coding SNP to cause a functional impact on the protein. This involved the use of PANTHER, SNAP, SIFT, PolyPhen-2, PROVEAN and nsSNPAnalyzer bioinformatics analytical tools in detecting harmful and beneficial effects at H57G, Y89R, V104D and Y112I substitutions in the peptide binding region of the DRB gene of Nigerian goats. The results from PANTHER analysis revealed that H57G, Y89R and Y112I substitutions (Pdeleterious= 0.113, 0.204 and 0.472, respectively) were beneficial; while that of V104D was deleterious (Pdeleterious= 0.756), an indication that it was non-neutral. As regards the SNAP approach, H57G and Y89R substitutions were returned neutral with expected accuracy of 53 and 69%, respectively while V104D and Y112I substitutions were harmful. H57G and Y89R substitutions were also found harmless in the SIFT analysis. However, only H57G (PROVEAN) and V104D (nsSNPAnalyzer) amino acid substitutions were found to be beneficial. Interestingly, the predicted 3D structures of both native and mutant DRB protein appeared similar as validated by Ramachandran plots. The consensus reached by PANTHER, SNAP, SIFT and PolyPhen-2 approaches on the neutrality especially of H57G (PROVEAN inclusive) and Y89R amino acid substitutions may be used in search of disease resistant genotypes at the DRB locus of Nigerian goats.
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Moaeen-Ud-Din, M., G. Bilal, and James Reecy. "Evolution of hypothalamus-pituitary growth axis among fish, amphibian, birds and mammals." Genetika 47, no. 2 (2015): 665–77. http://dx.doi.org/10.2298/gensr1502665m.
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Hypothalamus-pituitary growth axis (HP growth axis) regulates animal growth and development in pre-natal and post natal life governed by many factors. However, until recently, the evolutionary history of this axis among lineages is not understood. Aim of the present study was to understand the major events in evolution and evolutionary history and trend of HP growth axis. The diversity among Homo sapience, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio and Xenopus laevis was determined for genes involved in HP growth axis in current study. Sequences of HP growth axis genes were retrieved from NCBI (http://www.ncbi.nlm.nih.gov/). Nucleotide diversity using Kimura?s two-parameter method; codon-based test of positive selection using the Nei-Gojobori; equality of evolutionary rate with Tajima's relative rate test and phylogenetic history using the RelTime method were estimated in MEGA6. Estimates of the coefficients of evolutionary differentiation based on nucleotides and amino acids substitution patterns of HP growth axis genes showed contrasting evolutionary patterns among the lineages. The results demonstrated that although these genes might have crucial functional roles in each of the species, however, their sequence divergence did not necessarily reflect similar molecular evolution among the species. Codon-based test of positive selection revealed that Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat had similar and higher non synonymous substitutions (P > 0.05). Higher rate of non-synonymous substitutions at similar orthologs level among species indicated a similar positive selection pressure in these species. Results for relative rate test assessed with the chi-squared test showed difference on unique mutations among lineages at synonymous and non synonymous sites except Chicken vs Mouse, Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat. This indicated that the mutagenic process that generates substitutional mutation is taking place at approximately the same rate at synonymous and non-synonymous sites these lineages. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of these species. This is the first demonstration that variable rates of molecular evolution may be present within HP growth axis genes among different species. This difference could be of interest for comparative genomics analysis and physiological genes functions identification among tho comparative genomics, evolution rate, HP growth axis, positive selection se species whose HP growth axis is not explored.
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Chatrou, Lars Willem, Michael David Pirie, Robin Van Velzen, and Freek Theodoor Bakker. "Annonaceae substitution rates: a codon model perspective." Revista Brasileira de Fruticultura 36, spe1 (2014): 108–17. http://dx.doi.org/10.1590/s0100-29452014000500013.
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The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these differences has led to inconsistent results when estimating the ages of clades in Annonaceae using molecular dating techniques. We ask whether these differences may be attributed to inappropriate modelling assumptions in the phylogenetic analyses. Specifically, we test for (clade-specific) differences in rates of non-synonymous and synonymous substitutions. A high ratio of nonsynonymous to synonymous substitutions may lead to similarity of DNA sequences due to convergence instead of common ancestry, and as a result confound phylogenetic analyses. We use a dataset of three chloroplast genes (rbcL, matK, ndhF) for 129 species representative of the family. We find that differences in branch lengths between major clades are not attributable to different rates of non-synonymous and synonymous substitutions. The differences in evolutionary rate between the major clades of Annonaceae pose a challenge for current molecular dating techniques that should be seen as a warning for the interpretation of such results in other organisms.
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Decaro, N., C. Desario, A. Miccolupo, M. Campolo, A. Parisi, V. Martella, F. Amorisco, M. S. Lucente, A. Lavazza, and C. Buonavoglia. "Genetic analysis of feline panleukopenia viruses from cats with gastroenteritis." Journal of General Virology 89, no. 9 (September 1, 2008): 2290–98. http://dx.doi.org/10.1099/vir.0.2008/001503-0.
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Thirty-nine parvovirus strains contained in faecal samples collected in Italy (n=34) and UK (n=5) from cats with feline panleukopenia were characterized at the molecular level. All viruses were proven to be true feline panleukopenia virus (FPLV) strains by a minor groove binder probe assay, which is able to discriminate between FPLV and the closely related canine parvovirus type 2. By using sequence analysis of the VP2 gene, it was found that the FPLV strains detected in Italy and UK were highly related to each other, with a nucleotide identity of 99.1–100 and 99.4–99.8 % among Italian and British strains, respectively, whereas the similarities between all the sequences analysed were 98.6–100 %. Eighty-eight variable positions were detected in the VP2 gene of the field and reference FPLV strains, most of which were singletons. Synonymous substitutions (n=57) predominated over non-synonymous substitutions (n=31), and the ratio between synonymous and non-synonymous substitutions (dN/dS) was 0.10, thus confirming that evolution of FPLV is driven by random genetic drift rather than by positive selection pressure. Some amino acid mutations in the VP2 protein affected sites that are thought to be responsible for antigenic and biological properties of the virus, but no clear patterns of segregation and genetic markers, were identified, confirming that FPLV is in evolutionary stasis.
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Rasmussen, H. B., and J. Clausen. "Large Number of Polymorphic Nucleotides and a Termination Codon in theenvGene of the Endogenous Human Retrovirus ERV3." Disease Markers 14, no. 3 (1998): 127–33. http://dx.doi.org/10.1155/1998/958379.
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The terminal portion of thepolgene and the entireenvgene of the human endogenous retrovirus ERV3 was screened for polymorphic nucleotides. For this purpose fragments amplified from the desired regions of ERV3 were subjected to single strand conformational analysis (SSCP analysis). Using this approach, we detected 13 polymorphic nucleotides, namely four in thepolgene and nine in theenvgene. Three of the nucleotide substitutions were synonymous (not affecting the amino acid code). One of the non-synonymous nucleotide substitutions changed an arginine codon to a termination codon. The alleles at the different polymorphic sites could be arranged into five ERV3 haplotypes, two of which were new.To evaluate the possible significance of the termination codon, which precludes expression of a putative immunoregulatory factor, we examined samples of DNA from patients with multiple sclerosis, a demyelinating disease of presumed autoimmune etiology. We did not find an association between the ERV3 allele with the termination codon and this disease.Perhaps the presence of a stop codon combined with the high number of non-synonymous nucleotide substitutions in the reading frame of theenvgene reflects absence of selective constraints during evolution. Obviously, our findings contradict the assumption that the reading frame of the ERV3envgene has been conserved throughout evolution.
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Morales, Juan G., Astrid E. Gaviria, and Elizabeth Gilchrist. "Allelic Variation and Selection in Effector Genes of Phytophthora infestans (Mont.) de Bary." Pathogens 9, no. 7 (July 9, 2020): 551. http://dx.doi.org/10.3390/pathogens9070551.
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Phytophthora infestans is a devastating plant pathogen in several crops such as potato (Solanum tuberosum), tomato (Solanum lycopersicum) and Andean fruits such as tree tomato (Solanum betaceum), lulo (Solanum quitoense), uchuva (Physalis peruviana) and wild species in the genus Solanum sp. Despite intense research performed around the world, P. infestans populations from Colombia, South America, are poorly understood. Of particular importance is knowledge about pathogen effector proteins, which are responsible for virulence. The present work was performed with the objective to analyze gene sequences coding for effector proteins of P. infestans from isolates collected from different hosts and geographical regions. Several genetic parameters, phylogenetic analyses and neutrality tests for non-synonymous and synonymous substitutions were calculated. Non-synonymous substitutions were identified for all genes that exhibited polymorphisms at the DNA level. Significant negative selection values were found for two genes (PITG_08994 and PITG_12737) suggesting active coevolution with the corresponding host resistance proteins. Implications for pathogen virulence mechanisms and disease management are discussed.
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Rola, Jerzy, Wojciech Socha, and Jan F. Żmudziński. "Sequence analysis of minor protein genes of equine arteritis virus during persistent infection." Bulletin of the Veterinary Institute in Pulawy 59, no. 2 (June 1, 2015): 179–84. http://dx.doi.org/10.1515/bvip-2015-0027.
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Abstract The variability of the ORF2a, ORF2b, ORF3, and ORF4 genes of the equine arteritis virus (EAV) was analysed during a seven year observation of persistent infection in a stallion of the Malopolska breed. A total of 11 semen samples were collected between 2004 and 2011. RNA of EAV isolates obtained from the semen of the stallion was amplified, sequenced, and compared with the sequences of other strains available in GenBank. Multiple nucleotide substitutions were found in sequences of the analysed regions, however, neither deletion nor insertions were detected. The highest number of point mutations (11-6 synonymous and 5 non-synonymous) were found in the ORF2b gene, and the lowest number of substitutions (6-5 synonymous and one non-synonymous) were found in the ORF2a gene. None of the identified mutations affected any of the glycosylation or phosphorylation sites of the minor EAV protein. Phylogenetic analysis of the ORF3 gene of EAV isolates showed that they grouped together within the cluster of European strains of EAV. Additionally, the ORF3 gene sequences of the isolates showed high (86.4% - 98.3%) similarity to the previously isolated Polish EAV strains.
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Perrin-Stowe, Tolulope I. N., Yasuko Ishida, Emily E. Terrill, Brian C. Hamlin, Linda Penfold, Lara M. Cusack, Jan Novakofski, Nohra E. Mateus-Pinilla, and Alfred L. Roca. "Prion Protein Gene (PRNP) Sequences Suggest Differing Vulnerability to Chronic Wasting Disease for Florida Key Deer (Odocoileus virginianus clavium) and Columbian White-Tailed Deer (O. v. leucurus)." Journal of Heredity 111, no. 6 (September 1, 2020): 564–72. http://dx.doi.org/10.1093/jhered/esaa040.
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Abstract Chronic wasting disease (CWD) is a fatal, highly transmissible spongiform encephalopathy caused by an infectious prion protein. CWD is spreading across North American cervids. Studies of the prion protein gene (PRNP) in white-tailed deer (WTD; Odocoileus virginianus) have identified non-synonymous substitutions associated with reduced CWD frequency. Because CWD is spreading rapidly geographically, it may impact cervids of conservation concern. Here, we examined the genetic vulnerability to CWD of 2 subspecies of WTD: the endangered Florida Key deer (O. v. clavium) and the threatened Columbian WTD (O. v. leucurus). In Key deer (n = 48), we identified 3 haplotypes formed by 5 polymorphisms, of which 2 were non-synonymous. The polymorphism c.574G>A, unique to Key deer (29 of 96 chromosomes), encodes a non-synonymous substitution from valine to isoleucine at codon 192. In 91 of 96 chromosomes, Key deer carried c.286G>A (G96S), previously associated with substantially reduced susceptibility to CWD. Key deer may be less genetically susceptible to CWD than many mainland WTD populations. In Columbian WTD (n = 13), 2 haplotypes separated by one synonymous substitution (c.438C>T) were identified. All of the Columbian WTD carried alleles that in other mainland populations are associated with relatively high susceptibility to CWD. While larger sampling is needed, future management plans should consider that Columbian WTD are likely to be genetically more vulnerable to CWD than many other WTD populations. Finally, we suggest that genetic vulnerability to CWD be assessed by sequencing PRNP across other endangered cervids, both wild and in captive breeding facilities.
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Siebert, Felicitas, Gesine Lühken, Josef Pallauf, and Georg Erhardt. "Mutation in porcine Zip4-like zinc transporter is associated with pancreatic zinc concentration and apparent zinc absorption." British Journal of Nutrition 109, no. 6 (July 11, 2012): 969–76. http://dx.doi.org/10.1017/s0007114512002772.
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The aim of the present study was to analyse the sequence variability of the porcine Zip4-like Zn transporter gene and the association of identified sequence variants with average daily gain, apparent Zn absorption, plasma Zn concentration and Zn concentration in the liver and pancreas. For the purpose of the study, two different sample sets were used. Set one, which was used for sequencing and association analysis, included mRNA from intestinal tissue from thirty-five piglets of a feeding trial. Sample set two consisted of forty-six samples of genomic DNA from sperm or tissue of wild boars and several pig breeds and was used to genotype animals of different breeds. The sequence analysis of porcine Zip4-like complementary DNA in sample set one revealed the presence of seven nucleotide substitutions. Of these, six were synonymous, whereas a substitution of A with C in exon IX (XM_001925360 c.1430A>C) causes an amino acid exchange from glutamic acid to alanine (p.Glu477Ala). The association analysis revealed no influence of the six synonymous substitutions on Zn values, but the non-synonymous nucleotide exchange significantly increased Zn concentration in the pancreas and apparent Zn absorption of the piglets in week 2 of the feeding trial. The parentage of the piglets and the genotyping results in sample set two suggest a breed-specific presence of the A allele in Piétrain for this amino acid substitution. These results indicate that genotype influences the Zn absorption abilities of individual animals, which should be taken into consideration in animal breeding as well as for the selection of experimental animals.
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Sitt, Tatjana, Roger Pelle, Maurine Chepkwony, W. Ivan Morrison, and Philip Toye. "Theileria parvaantigens recognized by CD8+ T cells show varying degrees of diversity in buffalo-derived infected cell lines." Parasitology 145, no. 11 (May 6, 2018): 1430–39. http://dx.doi.org/10.1017/s0031182018000264.
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AbstractThe extent of sequence diversity among the genes encoding 10 antigens (Tp1–10) known to be recognized by CD8+T lymphocytes from cattle immune toTheileria parvawas analysed. The sequences were derived from parasites in 23 buffalo-derived cell lines, three cattle-derived isolates and one cloned cell line obtained from a buffalo-derived stabilate. The results revealed substantial variation among the antigens through sequence diversity. The greatest nucleotide and amino acid diversity were observed in Tp1, Tp2 and Tp9. Tp5 and Tp7 showed the least amount of allelic diversity, and Tp5, Tp6 and Tp7 had the lowest levels of protein diversity. Tp6 was the most conserved protein; only a single non-synonymous substitution was found in all obtained sequences. The ratio of non-synonymous: synonymous substitutions varied from 0.84 (Tp1) to 0.04 (Tp6). Apart from Tp2 and Tp9, we observed no variation in the other defined CD8+ T cell epitopes (Tp4, 5, 7 and 8), indicating that epitope variation is not a universal feature ofT. parvaantigens. In addition to providing markers that can be used to examine the diversity inT. parvapopulations, the results highlight the potential for using conserved antigens to develop vaccines that provide broad protection againstT. parva.
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Malyarchuk, Boris A., and Miroslava V. Derenko. "Polymorphism of the genes encoding for the carnitine acyltransferases in native populations of Siberia." Ecological genetics 15, no. 4 (December 25, 2017): 13–18. http://dx.doi.org/10.17816/ecogen15413-18.
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Background. Exome polymorphism is a rich source of information on the structure and function of proteins and metabolic pathways. The traditional diet of native populations of Northeast Asia (Eskimos, Chukchi and Koryaks) is enriched with fatty acids, which presupposes the existence of adaptive rearrangements of the lipid metabolism system among northern aborigines. Carnitine acyltransferases are the most important group of enzymes that metabolize fatty acids.
Materials and methods. To study adaptive changes in the genes encoding for the carnitine acyltransferases, we performed a screening of polymorphisms in the exons of CPT1A, CPT1B, CPT1C, CPT2, CRAT, and CROT genes in various populations of native inhabitants of Siberia.
Results. In exons of five genes (with the exception of CROT), 16 non-synonymous substitutions were identified. Of these, three substitutions were detected at high frequencies in populations of Northeast Asia (in Eskimos, Chukchi and Koryaks): at the loci rs80356779 of the CPT1A gene (replacement of P479L) and rs763273578 of the CPT1C gene (T740A), as well as a new polymorphism at position 131866581 of chromosome 9 at the CRAT gene (S99F). Exome analysis showed that among native populations of Northeast Asia, new non-synonymous substitutions with high pathogenicity indices appeared in the genes of energy metabolism and lipid exchange (genes GK2, ABHD6, NCOA2, OSPL3, LRP10, TTN, and PTTG2).
Conclusion. It is assumed that new variants of non-synonymous polymorphism arose as a result of genetic adaptation of native peoples to the extremely cold climate and a specific “Arctic” diet of aborigines of the Far North.
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Buriachenko, S. V., and B. T. Stegniy. "Variable loci of HA, NA and NP genes as effective RNA targets for genotyping subtypes H1N1 and H7N9." Faktori eksperimental'noi evolucii organizmiv 25 (August 30, 2019): 111–14. http://dx.doi.org/10.7124/feeo.v25.1149.
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Aim. Influenza viruses are a serious pathogen of humans, animals and birds that regularly cause epidemics. Antigenic variability and reassortment of influenza A virus genes represent a high level of neonatal data, which does not allow to assess the evolutionary stability of proteins. Determination of variable HA, NA and NP gene loci of two different antigenic subtypes of the H1 and H7 influenza virus will allow the establishment of RNA targets for genotyping. Methods. An analysis of substitution of nucleotides in the encoding regions of influenza A subtype genes of various antigenic subtypes obtained from the GenBank database using the MEGA 6.0 program determined the fate of synonymous and non-synonymous substitutions in each position of multiple alignments of the coding regions of the nucleotide sequences using the BLAST algorithm. The analysis of variable locus of proteins was determined by the DISORDER algorithm. Results. Different types of mutations are found in variable locus of the studied genes. The most variable genes are HA and NA, the least NP. In sequences of the NP gene synonymous nucleotide substitutions prevail. The genome of NA is mainly deletions and insertions. Conclusions. The variability of the nucleotide sequences of the HA, NA and NP genes in the subtypes A H1 and H7 was detected. It has been established that the use of variable locus of these genes allows for the identification of influenza A strains and identifies a separate serotype.Keywords: neurominidase, variability, genetic markers, target RNA, genotyping.
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Ryynänen, Heikki J., and Craig R. Primmer. "Varying signals of the effects of natural selection during teleost growth hormone gene evolution." Genome 49, no. 1 (January 1, 2006): 42–53. http://dx.doi.org/10.1139/g05-079.
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The growth hormone (GH) gene of teleost fish exhibits a higher degree of variability compared with other vertebrate groups. However, the different selective constraints at the sequence level are not well understood. In this study, maximum-likelihood (ML) models of codon substitutions were used to investigate Darwinian adaptive evolution of the GH gene in teleost fishes. Complete GH gene sequences of 54 fish species were classified into 4 orders, and the variable nature of GH was examined by determining the dN and dS rate variation and the rates of molecular evolution for each teleost order. The results indicate that although the overall evolution rate for teleost GH is high ((1.15 ± 0.01) × 10–9 substitutions/(aa site·y)) compared with the "slow phases" in mammals ((0.21 to 0.28 ± 0.05) × 10–9), the vital structure of this gene has been retained. While the majority of the amino acid changes appear to be due to relaxation of purifying selection, some positively selected sites were detected in regions with no specifically identified role in protein function. The positively selected regions observed in salmoniformes lineage suggests a possible role for positive selection driving functional divergence in paralogous forms of the GH gene after whole-genome duplication in this lineage.Key words: teleost fish, growth hormone, positive selection, synonymous substitution, non-synonymous substitution, molecular evolution.
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Shirai, Kazumasa, Nobuyuki Inomata, Shinji Mizoiri, Mitsuto Aibara, Yohey Terai, Norihiro Okada, and Hidenori Tachida. "High prevalence of non-synonymous substitutions in mtDNA of cichlid fishes from Lake Victoria." Gene 552, no. 2 (December 2014): 239–45. http://dx.doi.org/10.1016/j.gene.2014.09.039.
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Vicens, Alberto, and David Posada. "Selective Pressures on Human Cancer Genes along the Evolution of Mammals." Genes 9, no. 12 (November 28, 2018): 582. http://dx.doi.org/10.3390/genes9120582.
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Cancer is a disease driven by both somatic mutations that increase survival and proliferation of cell lineages and the evolution of genes associated with cancer risk in populations. Several genes associated with cancer in humans, hereafter cancer genes, show evidence of germline positive selection among species. Taking advantage of a large collection of mammalian genomes, we systematically looked for signatures of germline positive selection in 430 cancer genes available in COSMIC. We identified 40 cancer genes with a robust signal of positive selection in mammals. We found evidence for fewer selective constraints—higher number of non-synonymous substitutions per non-synonymous site to the number of synonymous substitutions per synonymous site (dN/dS)—and higher incidence of positive selection—more positively selected sites—in cancer genes bearing germline and recessive mutations that predispose to cancer. This finding suggests a potential association between relaxed selection, positive selection, and risk of hereditary cancer. On the other hand, we did not find significant differences in terms of tissue or gene type. Human cancer genes under germline positive selection in mammals are significantly enriched in the processes of DNA repair, with high presence of Fanconi anaemia/Breast Cancer A (FA/BRCA) pathway components and T cell proliferation genes. We also show that the inferred positively selected sites in the two genes with the strongest signal of positive selection, i.e., BRCA2 and PTPRC, are in regions of functional relevance, which could be relevant to cancer susceptibility.
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Yakubu, Abdulmojeed, Adebowale Salako, Donato de, Michael Takeet, Sunday Peters, Moses Okpeku, Mathew Wheto, and Ikhide Imumorin. "Nucleotide sequence variability analysis of Major Histocompatibility Complex Class II DQA1 gene in Nigerian goats." Genetika 49, no. 3 (2017): 865–74. http://dx.doi.org/10.2298/gensr1703865y.
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Major Histocompatibility Complex (MHC) molecules loaded with peptides derived from invading pathogens are recognised by the immune system to produce a highly effective and specific response against foreign pathogens. A 310-bp fragment of exon 2 of the MHC Class II DQA1 gene was amplified in 27 animals made up of three major Nigerian goat breeds [West African Dwarf (WAD), Red Sokoto (RS) and Sahel (SH)]. Twenty amino acid polymorphic sites were found in Nigerian goats. Comparison of predicted amino acid residues of DQA1 exon 2 alleles of Nigerian goats with similar alleles from other caprine species revealed considerable congruence in amino acid substitution pattern. A significant positive selection signature was detected at the DQA1 locus of Nigerian goats in that non-synonymous substitutions occurred at a faster rate compared to synonymous substitutions (dN:dS ratio = 1.28 ; Z-Statistics= 1.634; P<0.05). The evolutionary tree constructed using UPGMA, revealed that the southern WAD goat appeared to be more related to the northern RS than SH goat at the DQA1 locus. It will be interesting therefore, for future studies to investigate the association of the genetic variants in DQA1 gene of Nigerian goats with resistance/susceptiblity to diseases in order to conserve these precious animal genetic resources.
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Nguyen, Linh-Phuong, Nicolas Galtier, and Benoit Nabholz. "Gene expression, chromosome heterogeneity and the fast-X effect in mammals." Biology Letters 11, no. 2 (February 2015): 20150010. http://dx.doi.org/10.1098/rsbl.2015.0010.
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The higher rate of non-synonymous over synonymous substitutions (dN/dS) of the X chromosome compared with autosomes is often interpreted as a consequence of X hemizygosity. However, other factors, such as gene expression, are also known to vary between X and autosomes. Analysing 4800 orthologues in six mammals, we found that gene expression levels, associated with GC content, fully account for the variation in dN/dS between X and autosomes with no detectable effect of hemizygosity. We also report an extensive variance in dN/dS and gene expression between autosomes.
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Leitch, E. C. McWilliam, J. Bendig, M. Cabrerizo, J. Cardosa, T. Hyypiä, O. E. Ivanova, A. Kelly, et al. "Transmission Networks and Population Turnover of Echovirus 30." Journal of Virology 83, no. 5 (December 17, 2008): 2109–18. http://dx.doi.org/10.1128/jvi.02109-08.
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ABSTRACT Globally, echovirus 30 (E30) is one of the most frequently identified enteroviruses and a major cause of meningitis. Despite its wide distribution, little is known about its transmission networks or the dynamics of its recombination and geographical spread. To address this, we have conducted an extensive molecular epidemiology and evolutionary study of E30 isolates collected over 8 years from a geographically wide sample base (11 European countries, Asia, and Australia). 3Dpol sequences fell into several distinct phylogenetic groups, interspersed with other species B serotypes, enabling E30 isolates to be classified into 38 recombinant forms (RFs). Substitutions in VP1 and 3Dpol regions occurred predominantly at synonymous sites (ratio of nonsynonymous to synonymous substitutions, 0.05) with VP1 showing a rapid substitution rate of 8.3 × 10−3 substitutions per site per year. Recombination frequency was tightly correlated with VP1 divergence; viruses differing by evolutionary distances of >0.1 (or 6 years divergent evolution) almost invariably (>97%) had different 3Dpol groups. Frequencies of shared 3Dpol groups additionally correlated with geographical distances, with Europe and South Asia showing turnover of entirely distinct virus populations. Population turnover of E30 was characterized by repeated cycles of emergence, dominance, and disappearance of individual RFs over periods of 3 to 5 years, although the existence and nature of evolutionary selection underlying these population replacements remain unclear. The occurrence of frequent “sporadic” recombinants embedded within VP1 groupings of other RFs and the much greater number of 3Dpol groups than separately identifiable VP1 lineages suggest frequent recombination with an external diverse reservoir of non-E30 viruses.
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Norman, Jane E., Matthew L. Jones, Neil V. Morgan, Jacqui Stockley, Martina E. Daly, Stuart J. Mundell, Steve P. Watson, and Andrew D. Mumford. "Functional Variations In Genes Encoding Platelet G-Protein Coupled Receptors In Unselected and Platelet Function Disorder Populations." Blood 122, no. 21 (November 15, 2013): 3511. http://dx.doi.org/10.1182/blood.v122.21.3511.3511.
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Abstract Introduction G-protein coupled receptors (GPCRs) are critical mediators of platelet responses to stimulatory and inhibitory agonists. In rare families with mild bleeding, it is recognised that heterozygous loss of function variations in platelet GPCR genes may diminish platelet agonist responses. However, the population prevalence of loss of function variations in these genes is unknown. We have utilised population databases and next generation sequencing from patients with inherited platelet function disorders (IPFD) to describe the extent of genetic variation in the major platelet GPCRs. We have also used predictive computation and a new consensus structure of GPCRs (Venkatakrishnan AJ et al.Nature 2013; 494) to estimate which variations confer loss of function. Methods We interrogated the ESP and 1000 genomes population datasets for single nucleotide (SNV) and insertion-deletion (indel) variations in the genes encoding 6 stimulatory (ADRA2A, F2R, F2RL3, P2RY1, P2RY12, TBXA2R) and 2 inhibitory (PTGER4, PTGIR) platelet GPCRs. Coding and splice region variations within the relevant Refseq transcripts were functionally annotated using the Polyphen-2, SIFT and FATHMM algorithms. Missense variations within GPCR transmembrane (TM) domains, were annotated manually by expressing the substitutions in Ballesteros-Weinstein nomenclature before comparison with the consensus GPCR structure. Missense variations in the N- and C-terminal regions (NR and CR) and the intra- and extra- cellular loops (ICL and ECL) were annotated by identifying the position of the substituted residue relative to experimentally confirmed or putative functional motifs. An identical analysis was performed using exome data from 31 unrelated patients with IPFD recruited through the UK GAPP study with clinical bleeding and abnormal platelet function by light transmission aggregation. Results In 7745 individuals from the ESP and 1000 genomes cohorts, we identified 332 SNV in the target regions of the 8 GPCR genes (40.5 variations/kb) comprising 183 non-synonymous and 148 synonymous coding variants and 4 variations within intronic splice regions. There were no indel variations. Functional annotation of the non-synonymous SNVs identified 41 that potentially conferred loss of function, distributed in all the target GPCRs but with low population frequency (minor allele frequency range 1-0.008%). Five SNVs affected the NT, including Gly48Asp and Arg47His substitutions at the PAR4 receptor thrombin/trypsin cleavage site. There were 12 SNVs affecting the TM domains, of which 4 were predicted to disrupt GPCR folding, including a TPα receptor Pro305Leu substitution within the structural N/DPXXY motif and the P2Y12 receptor Met108Leu and Thr283Ile substitutions predicted to disrupt non-covalent TM network contacts. There were 14 SNVs affecting the ICL including the P2Y12 receptor Asp121Asn substitution in the E/DRY motif and prostacyclin (IP1) receptor Arg212Cys and Arg215Cys substitutions predicted to disrupt Gs coupling. Ten functional SNVs affected the CT. In 31 IPFD patients with complex laboratory phenotypes that could not be explained by loss of a single GPCR, there were 8 non-synonymous SNVs, of which 5 were predicted to confer loss of function (table). Discussion In unselected populations, heterozygous loss of function GPCR gene variations which potentially affect platelet agonist responses are individually rare, but collectively numerous. Loss of function GPCR variations were also present in patients with underlying IPFD. These data illustrate that variations in platelet regulatory genes may act as modifiers of laboratory phenotype in patients with underlying IPFD and that the net phenotype may be the product of multiple gene defects. Disclosures: No relevant conflicts of interest to declare.
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Sato, S., C. Ohnishi, Y. Uemoto, and E. Kobayashi. "Haplotype analysis within quantitative trait locus affecting intramuscular fat content on porcine chromosome." Czech Journal of Animal Science 56, No. 12 (December 22, 2011): 521–28. http://dx.doi.org/10.17221/4414-cjas.
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Previous results of fine mapping for quantitative trait loci affecting intramuscular fat content identified a 3.0-Mb chromosome interval on porcine chromosome 7, which contains at least 9 genes, based on the pig genome assembly. Therefore, we proposed these nine genes (LOC100154481, LOC100155711, LOC100155276, SPATA7, PTPN21, ZCH14, EML5, TTC8, and FOXN3) as positional candidate genes. The coding exons of the nine genes were characterized, and 45 polymorphisms were detected in F<sub>2</sub> Duroc × Meishan population. Within the nine genes, 10 non-synonymous substitutions and 1 insertion were genotyped among three European breeds (Landrace, Large White, and Duroc) and 1 Chinese breed (Meishan). Genotyping data was used to perform the haplotype analysis. Polymorphisms were found in all the studied genes, except ZCH14. We surveyed the frequency of 33 haplotypes that formed non-synonymous substitutions in four breeds. One of them was distributed widely in the Landrace, Large White, and Meishan breeds, but not in Duroc. Each breed had different major haplotypes.
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Quesada, Humberto, Mary Warren, and David O. F. Skibinski. "Nonneutral Evolution and Differential Mutation Rate of Gender-Associated Mitochondrial DNA Lineages in the Marine Mussel Mytilus." Genetics 149, no. 3 (July 1, 1998): 1511–26. http://dx.doi.org/10.1093/genetics/149.3.1511.
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Abstract Mussels have two types of mitochondrial DNA (mtDNA). The M type is transmitted paternally, and the F type is transmitted maternally. To test hypotheses of the molecular evolution of both mtDNA genomes, 50 nucleotide sequences were obtained for 396 bp of the COIII gene of European populations of Mytilus edulis and the Atlantic and Mediterranean forms of M. galloprovincialis. Analysis based on the proportion of synonymous and nonsynonymous substitutions indicate that mtDNA is evolving in a non-neutral and complex fashion. Previous studies on American mussels demonstrated that the F genome experiences a higher purifying selection and that the M genome evolves faster. Here we show that these patterns also hold in European populations. However, in contrast to American populations, where an excess of replacement substitution between F and M lineages has been reported, a significant excess of replacement polymorphism within mtDNA lineages is observed in European populations of M. galloprovincialis.European populations also show an excess of replacement polymorphism within the F but not within the M genome with respect to American M. trossulus, as well as a consistent pattern of excess of rare variants in both F and M genomes. These results are consistent with a nearly neutral model of molecular evolution and a recent relaxation of selective constraints on European mtDNA. Levels of diversity are significantly higher for the M than F genome, and the M genome also accumulates synonymous and nonsynonymous substitutions at a higher rate, in contrast with earlier reports where no difference for the synonymous rate was observed. It is suggested that a subtle balance between relaxed selection and a higher mutation rate explains the faster evolutionary rate of the M lineage.
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Rehman, Umar, Nighat Sultana, Abdullah, Abbas Jamal, Maryam Muzaffar, and Peter Poczai. "Comparative Chloroplast Genomics in Phyllanthaceae Species." Diversity 13, no. 9 (August 26, 2021): 403. http://dx.doi.org/10.3390/d13090403.
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Family Phyllanthaceae belongs to the eudicot order Malpighiales, and its species are herbs, shrubs, and trees that are mostly distributed in tropical regions. Here, we elucidate the molecular evolution of the chloroplast genome in Phyllanthaceae and identify the polymorphic loci for phylogenetic inference. We de novo assembled the chloroplast genomes of three Phyllanthaceae species, i.e., Phyllanthus emblica, Flueggea virosa, and Leptopus cordifolius, and compared them with six other previously reported genomes. All species comprised two inverted repeat regions (size range 23,921–27,128 bp) that separated large single-copy (83,627–89,932 bp) and small single-copy (17,424–19,441 bp) regions. Chloroplast genomes contained 111–112 unique genes, including 77–78 protein-coding, 30 tRNAs, and 4 rRNAs. The deletion/pseudogenization of rps16 genes was found in only two species. High variability was seen in the number of oligonucleotide repeats, while guanine-cytosine contents, codon usage, amino acid frequency, simple sequence repeats, synonymous and non-synonymous substitutions, and transition and transversion substitutions were similar. The transition substitutions were higher in coding sequences than in non-coding sequences. Phylogenetic analysis revealed the polyphyletic nature of the genus Phyllanthus. The polymorphic protein-coding genes, including rpl22, ycf1, matK, ndhF, and rps15, were also determined, which may be helpful for reconstructing the high-resolution phylogenetic tree of the family Phyllanthaceae. Overall, the study provides insight into the chloroplast genome evolution in Phyllanthaceae.
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Spatz, Stephen J., Lawrence Petherbridge, Yuguang Zhao, and Venugopal Nair. "Comparative full-length sequence analysis of oncogenic and vaccine (Rispens) strains of Marek's disease virus." Journal of General Virology 88, no. 4 (April 1, 2007): 1080–96. http://dx.doi.org/10.1099/vir.0.82600-0.
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The complete DNA sequence of the Marek's disease virus serotype 1 vaccine strain CVI988 was determined and consists of 178 311 bp with an overall gene organization identical to that of the oncogenic strains. In examining open reading frames (ORFs), nine differ between vaccine and oncogenic strains. A 177 bp insertion was identified in the overlapping genes encoding the Meq, RLORF6 and 23 kDa proteins of CVI988. Three ORFs are predicted to encode truncated proteins. One, designated 49.1, overlaps the gene encoding the large tegument protein UL36 and encodes a severely truncated protein of 34 aa. The others, ORF5.5/ORF75.91 and ORF3.0/78.0, located in the repeat regions (diploid), encode a previously unidentified ORF of 52 aa and a truncated version of the virus-encoded chemokine (vIL-8), respectively. Subtle genetic changes were identified in the two ORFs encoding tegument proteins UL36 and UL49. Only one diploid ORF (ORF6.2/ORF75.6) present in the genomes of the three virulent strains is absent in the CVI988-BAC genome. Seventy non-synonymous amino acid substitutions were identified that could differentiate CVI988-BAC from all three oncogenic strains collectively. Estimates of the non-synonymous to synonymous substitution ratio (ω) indicate that CVI988 ORFs are generally under purifying selection (ω<1), whereas UL39, UL49, UL50, RLORF6 and RLORF7 (Meq) appear to evolve under relaxed selective constraints. No CVI988 ORF was found to be under positive evolutionary selection (ω≫1).
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Van Nynatten, Alexander, Francesco H. Janzen, Kristen Brochu, Javier A. Maldonado-Ocampo, William G. R. Crampton, Belinda S. W. Chang, and Nathan R. Lovejoy. "To see or not to see: molecular evolution of the rhodopsin visual pigment in neotropical electric fishes." Proceedings of the Royal Society B: Biological Sciences 286, no. 1906 (July 10, 2019): 20191182. http://dx.doi.org/10.1098/rspb.2019.1182.
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Functional variation in rhodopsin, the dim-light-specialized visual pigment, frequently occurs in species inhabiting light-limited environments. Variation in visual function can arise through two processes: relaxation of selection or adaptive evolution improving photon detection in a given environment. Here, we investigate the molecular evolution of rhodopsin in Gymnotiformes, an order of mostly nocturnal South American fishes that evolved sophisticated electrosensory capabilities. Our initial sequencing revealed a mutation associated with visual disease in humans. As these fishes are thought to have poor vision, this would be consistent with a possible sensory trade-off between the visual system and a novel electrosensory system. To investigate this, we surveyed rhodopsin from 147 gymnotiform species, spanning the order, and analysed patterns of molecular evolution. In contrast with our expectation, we detected strong selective constraint in gymnotiform rhodopsin, with rates of non-synonymous to synonymous substitutions lower in gymnotiforms than in other vertebrate lineages. In addition, we found evidence for positive selection on the branch leading to gymnotiforms and on a branch leading to a clade of deep-channel specialized gymnotiform species. We also found evidence that deleterious effects of a human disease-associated substitution are likely to be masked by epistatic substitutions at nearby sites. Our results suggest that rhodopsin remains an important component of the gymnotiform sensory system alongside electrolocation, and that photosensitivity of rhodopsin is well adapted for vision in dim-light environments.
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Calado, Cecília R. C. "VARIABILITY OF NEUTROPHIL-ACTIVATING PROTEIN AMONG HELICOBACTER PYLORI STRAINS." Romanian Archives of Microbiology and Immunology 80, no. 1 (March 30, 2021): 43–50. http://dx.doi.org/10.54044/rami.2021.01.06.
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The Helicobacter pylori neutrophil activating protein (NAP) presents relevant inflammatory and immunomodulatory activity and has consequently been explored as a diagnosis and therapeutic target. In the present work, nap gene sequences, retrieved from H. pylori isolated world-wide, were analyzed, a high genetic diversity (with 88% of alleles) being observed in accordance with other virulence factors. The phylogenetic analysis did not reveal the separation of strains per geographical region according to a bacterial panmictic population. When compared to other genes of virulence factors of H. pylori, such as the vacuolating cytotoxin A (vacA), nap presents slightly lower genetic variability, concerning the number of alleles and polymorphic sites, pointing to a possible lower pressure of the host immune system. The nap genetic diversity is associated to a high proportion of synonymous substitutions in relation to non-synonymous substitutions, pointing to equilibrium between the need for antigenic diversity as a mechanism to escape the host immune system and the maintenance of the proteins function. All this information could be put to good use when planning the NAP application as a therapeutic or diagnostic target.
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Leyva-Hernández, Sandra, Ricardo Fong-Zazueta, Luis Medrano-González, and Ana Julia Aguirre-Samudio. "The evolution of brain size among the Homininae and selection at ASPM and MCPH1 genes." Biosis: Biological Systems 2, no. 2 (June 22, 2021): 293–310. http://dx.doi.org/10.37819/biosis.002.02.0104.
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We examined the evolutionary relationship of the ASPM (abnormal spindle-like microcephaly associated) and MCPH1 (microcephalin-1) genes with brain volume among humans and other primates. We obtained sequences of these genes from 14 simiiform species including hominins. Two phylogenetic analyses of ASPM exon 3 and MCPH1 exons 8 and 11 were performed to maximize taxon sampling or sequence extension to compare the nucleotide substitution and encephalization rates, and examine signals of selection. Further assessment of selection among humans was done through the analysis of non-synonymous and synonymous substitutions (dN/dS), and linkage disequilibrium (LD) patterns. We found that the accelerated evolution of brain size in hominids, is related to synchronic acceleration in the substitution rates of ASPM and MCPH1, and to signals of positive selection, especially in hominins. The dN/dS and LD analyses in Homo detected sites under positive selection and some regions with haplotype blocks at several candidate sites surrounded by blocks in LD-equilibrium. Accelerations and signals of positive selection in ASPM and MCPH1 occurred in different lineages and periods being ASPM more closely related with the brain evolution of hominins. MCPH1 evolved under positive selection in different lineages of the Catarrhini, suggesting independent evolutionary roles of this gene among primates.
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Lucaci, Alexander G., Sadie R. Wisotsky, Stephen D. Shank, Steven Weaver, and Sergei L. Kosakovsky Pond. "Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes." PLOS ONE 16, no. 3 (March 12, 2021): e0248337. http://dx.doi.org/10.1371/journal.pone.0248337.
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Despite many attempts to introduce evolutionary models that permit substitutions to instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible or are reflective of non-biological artifacts, such as alignment errors. Codon models continue to posit that only single nucleotide change have non-zero rates. Here, we develop and test a simple hierarchy of codon-substitution models with non-zero evolutionary rates for only one-nucleotide (1H), one- and two-nucleotide (2H), or any (3H) codon substitutions. Using over 42, 000 empirical alignments, we find widespread statistical support for multiple hits: 61% of alignments prefer models with 2H allowed, and 23%—with 3H allowed. Analyses of simulated data suggest that these results are not likely to be due to simple artifacts such as model misspecification or alignment errors. Further modeling reveals that synonymous codon island jumping among codons encoding serine, especially along short branches, contributes significantly to this 3H signal. While serine codons were prominently involved in multiple-hit substitutions, there were other common exchanges contributing to better model fit. It appears that a small subset of sites in most alignments have unusual evolutionary dynamics not well explained by existing model formalisms, and that commonly estimated quantities, such as dN/dS ratios may be biased by model misspecification. Our findings highlight the need for continued evaluation of assumptions underlying workhorse evolutionary models and subsequent evolutionary inference techniques. We provide a software implementation for evolutionary biologists to assess the potential impact of extra base hits in their data in the HyPhy package and in the Datamonkey.org server.
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Chivero, Ernest T., Nirjal Bhattarai, Robert T. Rydze, Mark A. Winters, Mark Holodniy, and Jack T. Stapleton. "Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and serum-derived viral RNA-containing particles are infectious in vitro." Journal of General Virology 95, no. 6 (June 1, 2014): 1307–19. http://dx.doi.org/10.1099/vir.0.063016-0.
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Human pegivirus (HPgV; previously called GB virus C/hepatitis G virus) has limited pathogenicity, despite causing persistent infection, and is associated with prolonged survival in human immunodeficiency virus-infected individuals. Although HPgV RNA is found in and produced by T- and B-lymphocytes, the primary permissive cell type(s) are unknown. We quantified HPgV RNA in highly purified CD4+ and CD8+ T-cells, including naïve, central memory and effector memory populations, and in B-cells (CD19+), NK cells (CD56+) and monocytes (CD14+) using real-time reverse transcription-PCR. Single-genome sequencing was performed on viruses within individual cell types to estimate genetic diversity among cell populations. HPgV RNA was present in CD4+ and CD8+ T-lymphocytes (nine of nine subjects), B-lymphocytes (seven of ten subjects), NK cells and monocytes (both four of five). HPgV RNA levels were higher in naïve (CD45RA+) CD4+ cells than in central memory and effector memory cells (P<0.01). HPgV sequences were highly conserved among subjects (0.117±0.02 substitutions per site; range 0.58–0.14) and within subjects (0.006±0.003 substitutions per site; range 0.006–0.010). The non-synonymous/synonymous substitution ratio was 0.07, suggesting a low selective pressure. Carboxyfluorescein succinimidyl ester (CFSE)-labelled HPgV RNA-containing particles precipitated by a commercial exosome isolation reagent delivered CSFE to uninfected monocytes, NK cells and T- and B-lymphocytes, and HPgV RNA was transferred to PBMCs with evidence of subsequent virus replication. Thus, HPgV RNA-containing serum particles including microvesicles may contribute to delivery of HPgV to PBMCs in vivo, explaining the apparent broad tropism of this persistent human RNA virus.
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Mitterboeck, T. Fatima, and Sarah J. Adamowicz. "Flight loss linked to faster molecular evolution in insects." Proceedings of the Royal Society B: Biological Sciences 280, no. 1767 (September 22, 2013): 20131128. http://dx.doi.org/10.1098/rspb.2013.1128.
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The loss of flight ability has occurred thousands of times independently during insect evolution. Flight loss may be linked to higher molecular evolutionary rates because of reductions in effective population sizes ( N e ) and relaxed selective constraints. Reduced dispersal ability increases population subdivision, may decrease geographical range size and increases (sub)population extinction risk, thus leading to an expected reduction in N e . Additionally, flight loss in birds has been linked to higher molecular rates of energy-related genes, probably owing to relaxed selective constraints on energy metabolism. We tested for an association between insect flight loss and molecular rates through comparative analysis in 49 phylogenetically independent transitions spanning multiple taxa, including moths, flies, beetles, mayflies, stick insects, stoneflies, scorpionflies and caddisflies, using available nuclear and mitochondrial protein-coding DNA sequences. We estimated the rate of molecular evolution of flightless (FL) and related flight-capable lineages by ratios of non-synonymous-to-synonymous substitutions (d N /d S ) and overall substitution rates (OSRs). Across multiple instances of flight loss, we show a significant pattern of higher d N /d S ratios and OSRs in FL lineages in mitochondrial but not nuclear genes. These patterns may be explained by relaxed selective constraints in FL ectotherms relating to energy metabolism, possibly in combination with reduced N e .
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Pal, Aruna, Arjava Sharma, T. K. Bhattacharya, P. N. Chatterjee, and A. K. Chakravarty. "Molecular Characterization and SNP Detection of CD14 Gene of Crossbred Cattle." Molecular Biology International 2011 (October 25, 2011): 1–13. http://dx.doi.org/10.4061/2011/507346.
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CD14 is an important molecule for innate immunity that can act against a wide range of pathogens. The present paper has characterized CD14 gene of crossbred (CB) cattle (Bos indicus×Bos taurus). Cloning and sequence analysis of CD14 cDNA revealed 1119 nucleotide long open reading frame encoding 373 amino acids protein and 20 amino acids signal peptide. CB cattle CD14 gene exhibited a high percentage of nucleotide identity (59.3–98.1%) with the corresponding mammalian homologs. Cattle and buffalo appear to have diverged from a common ancestor in phylogenetic analysis. 25 SNPs with 17 amino acid changes were newly reported and the site for mutational hot-spot was detected in CB cattle CD14 gene. Non-synonymous substitutions exceeding synonymous substitutions indicate the evolution of this protein through positive selection among domestic animals. Predicted protein structures obtained from deduced amino acid sequence indicated CB cattle CD14 molecule to be a receptor with horse shoe-shaped structure. The sites for LPS binding, LPS signalling, leucine-rich repeats, putative N-linked glycosylation, O-linked glycosylation, glycosyl phosphatidyl inositol anchor, disulphide bridges, alpha helix, beta strand, leucine rich nuclear export signal, leucine zipper and domain linker were predicted. Most of leucine and cysteine residues remain conserved across the species.
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Isokpehi, Raphael D., Hari H. P. Cohly, Matthew N. Anyanwu, Rajendram V. Rajnarayanan, Paul B. Tchounwou, Udensi K. Udensi, and Barbara E. Graham-Evans. "Candidate Single Nucleotide Polymorphism Markers for Arsenic Responsiveness of Protein Targets." Bioinformatics and Biology Insights 4 (January 2010): BBI.S5498. http://dx.doi.org/10.4137/bbi.s5498.
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Arsenic is a toxic metalloid that causes skin cancer and binds to cysteine residues—a property that could be used to infer arsenic responsiveness of a target protein. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) result in amino acid substitutions and may alter arsenic binding with cysteine residues. Thus, the objective of this investigation was to identify and analyze nsSNPs that lead to substitutions to or from cysteine residues as an indication of increased or decreased arsenic responsiveness. We hypothesize that integration of data on molecular impacts of nsSNPs and arsenic-gene relationships will identify nsSNPs that could serve as arsenic responsiveness markers. We have analyzed functional and structural impacts data for 5,811 nsSNPs linked to 1,224 arsenic-annotated genes. In addition to the identified candidate nsSNPs for increased or reduced arsenic responsiveness, we observed i) a nsSNP that results in the breakage of a disulfide bond, as candidate marker for reduced arsenic responsiveness of KLK7, a secreted serine protease participate in normal shedding of the skin; and ii) 6 pairs of vicinal cysteines in KLK7 protein that could be binding sites for arsenic. In summary, our analysis identified non-synonymous SNPs that could be used to evaluate responsiveness of a protein target to arsenic. In particular, an epidermal expressed serine protease with crucial function in normal skin physiology was prioritized on the basis of abundance of vicinal cysteines for further research on arsenic-induced keratinocyte carcinogenesis.
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Kiaris, Hippokratis, and Athanasios G. Papavassiliou. "Allelic Frequency in Human SNPs Predicts the Rate of Non-Synonymous Nucleotide Substitutions between Human and Chimpanzee Genes." Advances in Anthropology 04, no. 01 (2014): 50–52. http://dx.doi.org/10.4236/aa.2014.41007.
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Martín, Susana, María Laura García, Antonella Troisi, Luis Rubio, Gonzalo Legarreta, Oscar Grau, Daniela Alioto, Pedro Moreno, and José Guerri. "Genetic variation of populations of Citrus psorosis virus." Journal of General Virology 87, no. 10 (October 1, 2006): 3097–102. http://dx.doi.org/10.1099/vir.0.81742-0.
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Citrus psorosis virus (CPsV), the type species of genus Ophiovirus, has a segmented, negative-stranded RNA genome. We examined the population structure and genetic variation of CPsV in three coding regions located in RNAs 1, 2 and 3, analysing 22 isolates from Argentina, California, Florida, Italy and Spain. Most isolates contained a predominant sequence and some minor variants. Estimations of the genetic diversity and phylogenetic clustering of isolates disclosed two populations, one comprising isolates from Spain, Italy, Florida and California and the other including the Argentinean isolates. Isolate CPV-4 (from Texas) included for comparison was distant from both groups, suggesting that it belongs to a third group. The low ratio between non-synonymous and synonymous nucleotide substitutions indicated strong selection for amino acid sequence conservation, particularly in the coat protein gene. Incongruent phylogenetic relationships in different genomic regions suggested that exchange of genomic segments may have contributed to CPsV evolution.
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Lukashov, Vladimir V., and Jaap Goudsmit. "Evolutionary relationships among Astroviridae." Journal of General Virology 83, no. 6 (June 1, 2002): 1397–405. http://dx.doi.org/10.1099/0022-1317-83-6-1397.
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To study the evolutionary relationships among astroviruses, all available sequences for members of the family Astroviridae were collected. Phylogenetic analysis distinguished two deep-rooted groups: one comprising mammalian astroviruses, with ovine astrovirus being an outlier, and the other comprising avian astroviruses. All virus species as well as serotypes of human astroviruses represented individual lineages within the tree. All human viruses clustered together and separately from non-human viruses, which argue for their common evolutionary origin and against ongoing animal-to-human transmissions. The branching order of mammalian astroviruses was exactly the opposite of that of their host species, suggesting at least two cross-species transmissions involving pigs, cats and humans, possibly through intermediate hosts. Analysis of synonymous (Ds) versus non-synonymous (Da) distances revealed that negative selection is dominating in the evolution of astroviruses, with the Ds:Da ratios being up to 46 for the comparisons of the most closely related viruses. Phylogenetic analyses of all open reading frames (ORFs) based on Ds resulted in the loss of tree structures, with virus species – and in ORF2, even serotypes of human astroviruses – branching out from virtually a single node, suggesting their ancient separation. The strong selection against non-synonymous substitutions, the low number of which is, therefore, not proof of a recent separation between lineages, together with the position of the oldest available human astrovirus strain (1971) far from the common node of its serotype 4, suggest that intraserotype diversification originates from an earlier date.
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Ratnakumar, Abhirami, Sylvain Mousset, Sylvain Glémin, Jonas Berglund, Nicolas Galtier, Laurent Duret, and Matthew T. Webster. "Detecting positive selection within genomes: the problem of biased gene conversion." Philosophical Transactions of the Royal Society B: Biological Sciences 365, no. 1552 (August 27, 2010): 2571–80. http://dx.doi.org/10.1098/rstb.2010.0007.
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The identification of loci influenced by positive selection is a major goal of evolutionary genetics. A popular approach is to perform scans of alignments on a genome-wide scale in order to find regions evolving at accelerated rates on a particular branch of a phylogenetic tree. However, positive selection is not the only process that can lead to accelerated evolution. Notably, GC-biased gene conversion (gBGC) is a recombination-associated process that results in the biased fixation of G and C nucleotides. This process can potentially generate bursts of nucleotide substitutions within hotspots of meiotic recombination. Here, we analyse the results of a scan for positive selection on genes on branches across the primate phylogeny. We show that genes identified as targets of positive selection have a significant tendency to exhibit the genomic signature of gBGC. Using a maximum-likelihood framework, we estimate that more than 20 per cent of cases of significantly elevated non-synonymous to synonymous substitution rates ratio ( d N / d S ), particularly in shorter branches, could be due to gBGC. We demonstrate that in some cases, gBGC can lead to very high d N / d S (more than 2). Our results indicate that gBGC significantly affects the evolution of coding sequences in primates, often leading to patterns of evolution that can be mistaken for positive selection.
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Vakulenko, Yulia, Andrei Deviatkin, and Alexander Lukashev. "Using Statistical Phylogenetics for Investigation of Enterovirus 71 Genotype A Reintroduction into Circulation." Viruses 11, no. 10 (September 25, 2019): 895. http://dx.doi.org/10.3390/v11100895.
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Neurovirulent enterovirus 71 (EV-A71) caused a massive epidemic in China in 2008–2011. While subgenotype C4 was the major causative agent, a few isolates were almost identical to the prototype EV-A71 strain and belonged to genotype A. This variant was allegedly extinct since 1970, and its identification in this epidemic suggests reintroduction of the archive virus. Regression analysis of genetic distances (TempEst software) was of moderate utility due to the low resolution of classical phylogenetic methods. Bayesian phylogenetic analysis (BEAST software) suggested artificial introduction event based on highly aberrant phylogenetic tree branch rates that differed by over three standard deviations from the mean substitution rate for EV71. Manual nucleotide-level analysis was used to further explore the virus spread pattern after introduction into circulation. Upon reintroduction, the virus accumulated up to seven substitutions in VP1, most of them non-synonymous and located within the capsid’s canyon or at its rims, compatible with readaptation of a lab strain to natural circulation.
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Lakhssassi, Kenza, Malena Serrano, Belén Lahoz, María Pilar Sarto, Laura Pilar Iguácel, José Folch, José Luis Alabart, and Jorge Hugo Calvo. "The LEPR Gene Is Associated with Reproductive Seasonality Traits in Rasa Aragonesa Sheep." Animals 10, no. 12 (December 21, 2020): 2448. http://dx.doi.org/10.3390/ani10122448.
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The aim of this study was to characterize and identify causative polymorphisms in the leptin receptor (LEPR) gene responsible for the seasonal variation of reproductive traits in sheep. Three reproductive seasonality traits were studied: the total days of anoestrous (TDA), the progesterone cycling months (P4CM) and the oestrous cycling months (OCM). In total, 18 SNPs were detected in 33 ewes with extreme values for TDA and OCM. Six SNPs were non-synonymous substitutions and two of them were predicted in silico as deleterious: rs596133197 and rs403578195. These polymorphisms were then validated in 239 ewes. The SNP rs403578195, located in exon 8 and leading to a change of alanine to glycine (Ala284Gly) in the extracellular domain of the protein, was associated with the OCM trait, being the G allele associated with a decrease of 12 percent of the OCM trait. Haplotype analyses also suggested the involvement of other non-synonymous SNP located in exon 20 (rs405459906). This SNP also produces an amino acid change (Lys1069Glu) in the intracellular domain of the protein and segregates independently of rs403578195. These results confirm for the first time the role of the LEPR gene in sheep reproductive seasonality.
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Singh, Yogita, Bijay Ranjan Mirdha, Randeep Guleria, Shehla Khalil, Ashutosh Panda, Rama Chaudhry, Anant Mohan, Sushil Kumar Kabra, Lalit Kumar, and Sanjay Kumar Agarwal. "Molecular detection of DHFR gene polymorphisms in Pneumocystis jirovecii isolates from Indian patients." Journal of Infection in Developing Countries 9, no. 11 (November 30, 2015): 1250–56. http://dx.doi.org/10.3855/jidc.6810.
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Introduction: Pneumocystis pneumonia (PCP) is an opportunistic life-threatening infection, especially for immunocompromised individuals. A trimethoprim-sulfamethoxazole (TMP-SMX) combination is commonly used for the treatment of PCP, targeting both dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) enzymes. Several studies have already shown that polymorphisms in the DHPS gene are associated with drug resistance. The present study analyzed DHFR gene polymorphisms in Pneumocystis jirovecii recovered from clinical samples from patients admitted to a tertiary care health center in New Delhi, India. Methodology: Detection of P. jirovecii was performed using Gomori methenamine silver staining (GMS) and nested polymerase chain reaction (PCR) assay targeting the mitochondrial large subunit ribosomal RNA (mt LSU rRNA) gene. The DHFR gene was amplified using nested PCR protocol and was sequenced for detection of polymorphisms. Results: Of 180 clinical samples, only 4% (7/180) were positive by GMS staining, and 10% (18/180) were positive by mt LSU rRNA PCR assay. Of these 18 positive samples, only 77% (14/18) were amplified by the DHFR gene PCR assay. A total of 16 nucleotide substitutions were observed in 42% (6/14) samples targeted for the DHFR gene, of which 8 nucleotide substitutions were synonymous and the rest were non-synonymous. Conclusions: The DHFR gene mutations found in this study may possibly indicate an association of process likely to contribute to therapeutic failure or an evolutionary process, and warrant continuous monitoring.
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Cigan, Vesna. "Collocations and Term Variation in Mechanical Engineering Discourse." Fluminensia 30, no. 2 (2018): 99–120. http://dx.doi.org/10.31820/f.30.2.3.
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Terminological collocations1 are one of the most typical and very frequent units of representation of concepts in many disciplines. Although traditionally considered to be unwelcome in terminology, synonymy is amply present in specialized languages. Consequently, the same phenomenon is reflected in terminological collocations. This paper aims to investigate synonymous collocations extracted from mechanical engineering texts in terms of the most frequent and relevant types of denominative variation in the selected English collocations as well as of their equivalents in German and Croatian. The analysis of variations in terminological collocations gives insight into the (non)substitutability of collocation constituents as one of the major characteristics of collocations. Extracted collocations are analysed within a two-tier framework structured at a paradigmatic and a syntagmatic level, which allows for the identification of the three types of term variation: morphological, syntagmatic and semantic. Focusing on the collocations with the structure noun + noun and adjective + noun the results show that constituents of both syntactic structures allow substitution. The denominative variants are prevalent in adjective + noun collocations in which synonymous lexical elements functioning as collocates do not entail a concept change (admissible load ↔ allowable load). Lexeme substitutions are also annotated in noun + noun collocations expressing a slightly different dimension or facet of the concept (face gear vs. crown gear vs. crown wheel). The majority of German equivalents are nominal compounds that outnumber their morphological variants offering multiple equivalences.
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Stewart, Donald T., Ellen R. Kenchington, Rama K. Singh, and Eleftherios Zouros. "Degree of Selective Constraint as an Explanation of the Different Rates of Evolution of Gender-Specific Mitochondrial DNA Lineages in the Mussel Mytilus." Genetics 143, no. 3 (July 1, 1996): 1349–57. http://dx.doi.org/10.1093/genetics/143.3.1349.
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Abstract Mussels of the genus Mytilus segregate for a maternally transmitted F lineage and a paternally transmitted M lineage of mitochondrial DNA. Previous studies demonstrated that these lineages are older than the species of the M. edulis complex and that the M lineage evolves faster than the F lineage. Here we show that the latter observation also applies to a region of the molecule with no assigned function. Sequence data for the mitochondrial COIII gene and the “unassigned” region of the F and M lineages of M. edulis and M. trossulus are used to evaluate various hypotheses that may account for the faster rate of evolution of the M lineage. Tests based on the proportion of synonymous and nonsynonymous substitutions suggest that the M lineage experiences relatively relaxed selection. Further support for this hypothesis comes from an examination of COIII amino acid substitutions at sites defined as either conserved or variable based on the pattern of variation in other mollusks and Drosophila. Most substitutions in the M lineage occur in regions that are also variable among non-Mytilus taxa. We suggest that these differences in selection pressure are a consequence of doubly uniparental mitochondrial DNA transmission in Mytilus.
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Krysiak, Michał, Stanisław Gawroński, Kazimierz Adamczewski, and Roman Kierzek. "ALS Gene Mutations in Apera Spica-Venti Confer Broad-Range Resistance to Herbicides." Journal of Plant Protection Research 51, no. 3 (July 1, 2011): 261–67. http://dx.doi.org/10.2478/v10045-011-0043-7.
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ALS Gene Mutations in Apera Spica-Venti Confer Broad-Range Resistance to Herbicides Several biotypes of wind bentgrass in Poland have been identified as being resistant to acetolactate synthase (ALS) inhibitors. We screened these weeds with chlorsulfuron and performed a whole-plant bioassay with a range of doses based on these four herbicides: chlorsulfuron, sulfosulfuron, propoxycarbazone-sodium and mesosulfuron-methyl + iodosulfuron-methyl-sodium mixture. Ten biotypes, diverse in their levels of resistance, were submitted for molecular tests. PCR amplification and sequencing of als domains demonstrated numerous single nucleotide polymorphisms. Nine biotypes showed non-synonymous substitutions in codon Pro197, changing it to Ser or Thr. Mutation in Pro197 conferred a high level of resistance to the tested herbicides. Analysis of four biotypes also revealed a substitution in the Ala122 codon, changing it to Val. In one biotype this substitution was not accompanied by Pro197 mutation and this biotype was resistant to chlorsulfuron and mesosulfuron + iodosulfuron, but not to sulfosulfuron or propoxycarbazone-sodium. Correspondence between mutations and levels of resistan ce to ALS inhibitors may support management of resistant weeds with the existing palette of herbicides.
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Sitterlé, Emilie, Alix T. Coste, Thomas Obadia, Corinne Maufrais, Murielle Chauvel, Natacha Sertour, Dominique Sanglard, Anne Puel, Christophe D’Enfert, and Marie-Elisabeth Bougnoux. "Large-scale genome mining allows identification of neutral polymorphisms and novel resistance mutations in genes involved in Candida albicans resistance to azoles and echinocandins." Journal of Antimicrobial Chemotherapy 75, no. 4 (January 10, 2020): 835–48. http://dx.doi.org/10.1093/jac/dkz537.
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Abstract Background The genome of Candida albicans displays significant polymorphism. Point mutations in genes involved in resistance to antifungals may either confer phenotypic resistance or be devoid of phenotypic consequences. Objectives To catalogue polymorphisms in azole and echinocandin resistance genes occurring in susceptible strains in order to rapidly pinpoint relevant mutations in resistant strains. Methods Genome sequences from 151 unrelated C. albicans strains susceptible to fluconazole and caspofungin were used to create a catalogue of non-synonymous polymorphisms in genes involved in resistance to azoles (ERG11, TAC1, MRR1 and UPC2) or echinocandins (FKS1). The potential of this catalogue to reveal putative resistance mutations was tested in 10 azole-resistant isolates, including 1 intermediate to caspofungin. Selected mutations were analysed by mutagenesis experiments or mutational prediction effect. Results In the susceptible strains, we identified 126 amino acid substitutions constituting the catalogue of phenotypically neutral polymorphisms. By excluding these neutral substitutions, we identified 22 additional substitutions in the 10 resistant strains. Among these substitutions, 10 had already been associated with resistance. The remaining 12 were in Tac1p (n = 6), Upc2p (n = 2) and Erg11p (n = 4). Four out of the six homozygous substitutions in Tac1p (H263Y, A790V, H839Y and P971S) conferred increases in azole MICs, while no effects were observed for those in Upc2p. Additionally, two homozygous substitutions (Y64H and P236S) had a predicted conformation effect on Erg11p. Conclusions By establishing a catalogue of neutral polymorphisms occurring in genes involved in resistance to antifungal drugs, we provide a useful resource for rapid identification of mutations possibly responsible for phenotypic resistance in C. albicans.