scholarly journals Enrichment in conservative amino acid changes among fixed and standing missense variations in slow evolving proteins

2019 ◽  
Author(s):  
Mingrui Wang ◽  
Dapeng Wang ◽  
Jun Yu ◽  
Shi Huang
Keyword(s):  
Amino Acid ◽  
Nucleotide Polymorphisms ◽  
1000 Genomes Project ◽  
Single Nucleotide ◽  
1000 Genomes ◽  
Substitution Saturation ◽  
Dating Method ◽  
Selection For ◽  
Project Data ◽  
Molecular Clock Dating

AbstractProteins were first used in the early 1960s to discover the molecular clock dating method and remain in common usage today in phylogenetic inferences based on neutral variations. To avoid substitution saturation, it is necessary to use slow evolving genes. However, it remains unclear whether fixed and standing missense changes in such genes may qualify as neutral. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Macaca monkey, we found that the fraction of conservative amino acid mismatches between species was significantly higher in slow evolving proteins. We also examined the single nucleotide polymorphisms (SNPs) by using the 1000 genomes project data and found that missense SNPs in slow evolving proteins also had higher fraction of conservative changes, especially for common SNPs, consistent with more natural selection for SNPs, particularly rare ones, in fast evolving proteins. These results suggest that fixed and standing missense variations in slow evolving proteins are more likely to be neutral and hence better qualified for use in phylogenetic inferences.

scholarly journals Ancestral Spectrum Analysis With Population-Specific Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Gang Shi ◽  
Qingmin Kuang
Keyword(s):  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
1000 Genomes Project ◽  
Specific Population ◽  
High Coverage ◽  
Single Nucleotide ◽  
Target Populations ◽  
1000 Genomes ◽  
Sequencing Studies ◽  
Best Linear Unbiased

With the advance of sequencing technology, an increasing number of populations have been sequenced to study the histories of worldwide populations, including their divergence, admixtures, migration, and effective sizes. The variants detected in sequencing studies are largely rare and mostly population specific. Population-specific variants are often recent mutations and are informative for revealing substructures and admixtures in populations; however, computational methods and tools to analyze them are still lacking. In this work, we propose using reference populations and single nucleotide polymorphisms (SNPs) specific to the reference populations. Ancestral information, the best linear unbiased estimator (BLUE) of the ancestral proportion, is proposed, which can be used to infer ancestral proportions in recently admixed target populations and measure the extent to which reference populations serve as good proxies for the admixing sources. Based on the same panel of SNPs, the ancestral information is comparable across samples from different studies and is not affected by genetic outliers, related samples, or the sample sizes of the admixed target populations. In addition, ancestral spectrum is useful for detecting genetic outliers or exploring co-ancestry between study samples and the reference populations. The methods are implemented in a program, Ancestral Spectrum Analyzer (ASA), and are applied in analyzing high-coverage sequencing data from the 1000 Genomes Project and the Human Genome Diversity Project (HGDP). In the analyses of American populations from the 1000 Genomes Project, we demonstrate that recent admixtures can be dissected from ancient admixtures by comparing ancestral spectra with and without indigenous Americans being included in the reference populations.

scholarly journals Enrichment in conservative amino acid changes among fixed and standing missense variations in slowly evolving proteins

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9983
Author(s):  
Mingrui Wang ◽  
Dapeng Wang ◽  
Jun Yu ◽  
Shi Huang
Keyword(s):  
Amino Acid ◽  
Molecular Evolution ◽  
Rhesus Macaques ◽  
Neutral Theory ◽  
Evolutionary Rates ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Protein Coding ◽  
Project Data ◽  
The Impact

The process of molecular evolution has many elements that are not yet fully understood. Evolutionary rates are known to vary among protein coding and noncoding DNAs, and most of the observed changes in amino acid or nucleotide sequences are assumed to be non-adaptive by the neutral theory of molecular evolution. However, it remains unclear whether fixed and standing missense changes in slowly evolving proteins are more or less neutral compared to those in fast evolving genes. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Rhesus Macaques (Macaca mulatta), we found that the fraction of conservative substitutions between species was significantly higher in their slowly evolving proteins. Similar results were obtained by using four different methods of scoring conservative substitutions, including three that remove the impact of substitution probability, where conservative changes require fewer mutations. We also examined the single nucleotide polymorphisms (SNPs) by using the 1000 Genomes Project data and found that missense SNPs in slowly evolving proteins also had a higher fraction of conservative changes, especially for common SNPs, consistent with more non-conservative substitutions and hence stronger natural selection for SNPs, particularly rare ones, in fast evolving proteins. These results suggest that fixed and standing missense variants in slowly evolving proteins are more likely to be neutral.

scholarly journals Molecular epidemiologic characteristics of hemagglutinin from five waves of avian influenza A (H7N9) virus infection, from 2013 to 2017, in Zhejiang Province, China

2021 ◽  
Author(s):  
Yi Sun ◽  
Haiyan Mao ◽  
Xiuyu Lou ◽  
Xinying Wang ◽  
Yin Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Zhejiang Province ◽  
Personal Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Amino Acid Mutations ◽  
Influenza Outbreaks ◽  
Epidemiological Characteristics ◽  
The Waves

AbstractThere have been five waves of influenza A (H7N9) epidemics in Zhejiang Province between 2013 and 2017. Although the epidemiological characteristics of the five waves have been reported, the molecular genetics aspects, including the phylogeny, evolution, and mutation of hemagglutinin (HA), have not been systematically investigated. A total of 154 H7N9 samples from Zhejiang Province were collected between 2013 and 2017 and sequenced using an Ion Torrent Personal Genome Machine. The starting dates of the waves were 16 March 2013, 1 July 2013, 1 July 2014, 1 July 2015, and 1 July 2016. Single-nucleotide polymorphisms (SNPs) and amino acid mutations were counted after the HA sequences were aligned. The evolution of H7N9 matched the temporal order of the five waves, among which wave 3 played an important role. The 55 SNPs and 14 amino acid mutations with high frequency identified among the five waves revealed the dynamic occurrence of mutation in the process of viral dissemination. Wave 3 contributed greatly to the subsequent epidemic of waves 4 and 5 of H7N9. Compared with wave 1, wave 5 was characterized by more mutations, including A143V and R148K, two mutations that have been reported to weaken the immune response. In addition, some amino acid mutations were observed in wave 5 that led to more lineages. It is necessary to strengthen the surveillance of subsequent H7N9 influenza outbreaks.

scholarly journals Melanocortin-4 Receptor (MC4R) gene polymorphism and its effect on growth traits in Madura cattle

2019 ◽  
Vol 44 (1) ◽  
pp. 38
Author(s):  
P. W. Prihandini ◽  
S. Sumadi ◽  
G. Suparta ◽  
D. Maharani
Keyword(s):  
Growth Traits ◽  
Balance Control ◽  
Direct Sequencing ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
Pcr Rflp ◽  
Reverse Primer ◽  
Selection For

Melanocortin-4 receptor (MC4R) gene has an important role in the regulation of feed intake and energy balance control. The objective of this study was to identify the single nucleotide polymorphisms (SNPs) of MC4R gene and their association with growth traits in Madura cattle. A total of 198 calves were used in this study.Forward primer: 5’-GTCGGGCGTCTTGTTCATC-3’and reverse primer: 5’-GCTTGTGTTTAGCATCGCGT-3’ were used to amplify approximately 493 bp of MC4R gene. The results showed that two SNPs, g.1133C>G and g.1108C>T were identified by direct sequencing. The PCR-RFLP method was performed to genotype all individuals studied based on SNP g.1133C>G, and its SNP was significantly associated with shoulder height (SH) at yearling age (P<0.05). Animals with GG genotype had a higher SH (110.35±6.40cm) than those with CC (102.00±8.00 cm) and CG genotype (105.96±6.23 cm). The SNP g.1133 C>G changed amino acid from valine to leucine. In conclusion, the SNP g.1133C>G of the MC4R gene may be used as a marker-assisted selection for SH trait in Madura cattle.

scholarly journals SINGLE-NUCLEOTIDE POLYMORPHISMS OF CALCIUM-SENSING RECEPTOR ENCODING GENE ASSOCIATED WITH CALCIUM KIDNEY STONE DISEASE IN BABYLON PROVINCE

2018 ◽  
Vol 11 (2) ◽  
pp. 417 ◽  
Author(s):  
Zahraa Isam ◽  
Rabab Omran ◽  
Ammad Hassan Mahmood
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Kidney Stone ◽  
Stone Disease ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Calcium Sensing Receptor ◽  
Single Nucleotide ◽  
Kidney Stone Disease ◽  
Calcium Sensing

  Objective: The calcium-sensing receptor (CASR) is a G-protein-coupled receptor that is mainly expressed in the parathyroid and the kidneys where it regulates parathyroid hormone secretion and renal tubular calcium reabsorption. Inactivating and activating CASR gene due to mutations severally caused hypercalcemia or hypocalcemia disorders. The aim of the study was to investigate the risk factor of CASR rs1801725 (Ala986Ser) patients with renal disease.Method: The blood samples were collected from 100 patients and divided into two groups, each one containing 50 samples; chronic kidney disease and end-stage renal disease, who admitted Merjan Teaching Hospital in Babylon Province, Iraq, from February to July 2016. In addition, healthy persons as a control group (50 samples). Genotyping of CASR single-nucleotide polymorphisms (SNP) was performed using a polymerase chain reaction technique, followed by single-strand conformation polymorphism. Accordingly, these DNA polymorphisms were confirmed using DNA sequencing.Results: The conformational haplotypes of CASR, exon7 NCBI Primer3plus reference were obtained in three patterns, including two, three, and four bands, due to the presence SNPs within the studied region. These SNPs leads to change three amino acid residues of CASR, including amino acid substitutions were Ala 128→ Ser 128, Leu 155→Tye 155, and Leu 156→ Ser 156 that may affect or modified the tertiary structure of the receptor, subsequently the function like the affinity to calcium ion may be effected.Conclusion: These results suggest that the variants of CASR SNP, namely, rs1801725 might be involved in susceptibility to kidney stone disease.

scholarly journals Spontaneous Mutations in thePlasmodium falciparumSarcoplasmic/ Endoplasmic Reticulum Ca2+-ATPase (PfATP6) Gene among Geographically Widespread Parasite Populations Unexposed to Artemisinin-Based Combination Therapies

2010 ◽  
Vol 55 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Kazuyuki Tanabe ◽  
Sedigheh Zakeri ◽  
Nirianne Marie Q. Palacpac ◽  
Manada Afsharpad ◽  
Milijaona Randrianarivelojosia ◽  
...  
Keyword(s):  
Amino Acid ◽  
South America ◽  
Artemisinin Resistance ◽  
Common Snps ◽  
Nucleotide Polymorphisms ◽  
Combination Therapies ◽  
Single Nucleotide ◽  
Baseline Information ◽  
A Minor ◽  
Parasite Populations

ABSTRACTRecent reports on the decline of the efficacy of artemisinin-based combination therapies (ACTs) indicate a serious threat to malaria control. The endoplasmic/sarcoplasmic reticulum Ca2+-ATPase ortholog ofPlasmodium falciparum(PfSERCA) has been suggested to be the target of artemisinin and its derivatives. It is assumed that continuous artemisinin pressure will affect polymorphism of the PfSERCA gene (serca) if the protein is the target. Here, we investigated the polymorphism ofsercain parasite populations unexposed to ACTs to obtain baseline information for the study of potential artemisinin-driven selection of resistant parasites. Analysis of 656 full-length sequences from 13 parasite populations in Africa, Asia, Oceania, and South America revealed 64 single nucleotide polymorphisms (SNPs), of which 43 were newly identified and 38 resulted in amino acid substitutions. No isolates showed L263E and S769N substitutions, which were reportedly associated with artemisinin resistance. Among the four continents, the number of SNPs was highest in Africa. In Africa, Asia, and Oceania, common SNPs, or those with a minor allele frequency of ≥0.05, were less prevalent, with most SNPs noted to be continent specific, whereas in South America, common SNPs were highly prevalent and often shared with those in Africa. Of 50 amino acid haplotypes observed, only one haplotype (3D7 sequence) was seen in all four continents (64%). Forty-eight haplotypes had frequencies of less than 5%, and 40 haplotypes were continent specific. The geographical difference in the diversity and distribution ofsercaSNPs and haplotypes lays the groundwork for assessing whether some artemisinin resistance-associated mutations and haplotypes are selected by ACTs.

A STRUCTURAL BIOINFORMATICS APPROACH TO THE ANALYSIS OF NONSYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS (nsSNPs) AND THEIR RELATION TO DISEASE

2007 ◽  
Vol 05 (06) ◽  
pp. 1297-1318 ◽  
Author(s):  
CATHERINE L. WORTH ◽  
G. RICHARD J. BICKERTON ◽  
ADRIAN SCHREYER ◽  
JULIA R. FORMAN ◽  
TAMMY M. K. CHENG ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Structure Prediction ◽  
Three Dimensional ◽  
Comparative Modeling ◽  
Divergent Evolution ◽  
Amino Acid Substitutions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Proteins

The prediction of the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) on function depends critically on exploiting all information available on the three-dimensional structures of proteins. We describe software and databases for the analysis of nsSNPs that allow a user to move from SNP to sequence to structure to function. In both structure prediction and the analysis of the effects of nsSNPs, we exploit information about protein evolution, in particular, that derived from investigations on the relation of sequence to structure gained from the study of amino acid substitutions in divergent evolution. The techniques developed in our laboratory have allowed fast and automated sequence-structure homology recognition to identify templates and to perform comparative modeling; as well as simple, robust, and generally applicable algorithms to assess the likely impact of amino acid substitutions on structure and interactions. We describe our strategy for approaching the relationship between SNPs and disease, and the results of benchmarking our approach — human proteins of known structure and recognized mutation.

scholarly journals An Approach to Identify Individual Functional Single Nucleotide Polymorphisms and Isoform MicroRNAs

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Ying Wang ◽  
Jidong Ru ◽  
Tao Jin ◽  
Ming Sun ◽  
Lizhu Jia ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Single Nucleotide Polymorphisms ◽  
Disease Risk ◽  
Software Tool ◽  
Mature Mirnas ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
1000 Genomes ◽  
Mirna Sequencing

MicroRNAs (miRNAs) and single nucleotide polymorphisms (SNPs) play important roles in disease risk and development, especially cancer. Importantly, when SNPs are located in pre-miRNAs, they affect their splicing mechanism and change the function of miRNAs. To improve disease risk assessment, we propose an approach and developed a software tool, IsomiR_Find, to identify disease/phenotype-related SNPs and isomiRs in individuals. Our approach is based on the individual’s samples, with SNP information extracted from the 1000 Genomes Project. SNPs were mapped to pre-miRNAs based on whole-genome coordinates and then SNP-pre-miRNA sequences were constructed. Moreover, we developed matpred2, a software tool to identify the four splicing sites of mature miRNAs. Using matpred2, we identified isomiRs and then verified them by searching within individual miRNA sequencing data. Our approach yielded biomarkers for biological experiments, mined functions of miRNAs and SNPs, improved disease risk assessment, and provided a way to achieve individualized precision medicine.

scholarly journals Inference of recent admixture using genotype data

2020 ◽  
Author(s):  
Peter Pfaffelhuber ◽  
Elisabeth Sester-Huss ◽  
Franz Baumdicker ◽  
Jana Naue ◽  
Sabine Lutz-Bonengel ◽  
...  
Keyword(s):  
State Of The Art ◽  
Forensic Genetics ◽  
Statistical Test ◽  
Genotype Data ◽  
1000 Genomes Project ◽  
Additional Information ◽  
1000 Genomes ◽  
Project Data ◽  
Ancestry Proportions ◽  
Individual Ancestry

AbstractThe inference of biogeographic ancestry (BGA) has become a focus of forensic genetics. Mis-inference of BGA can have profound unwanted consequences for investigations and society. We show that recent admixture can lead to misclassification and erroneous inference of ancestry proportions, using state of the art analysis tools with (i) simulations, (ii) 1000 genomes project data, and (iii) two individuals analyzed using the ForenSeq DNA Signature Prep Kit. Subsequently, we extend existing tools for estimation of individual ancestry (IA) by allowing for different IA in both parents, leading to estimates of parental individual ancestry (PIA), and a statistical test for recent admixture. Estimation of PIA outperforms IA in most scenarios of recent admixture. Furthermore, additional information about parental ancestry can be acquired with PIA that may guide casework.

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