scholarly journals In silico analysis of Beta-Lactoglobulin gene in some selected mammalian species

2015 ◽  
Vol 31 (3) ◽  
pp. 327-338
Author(s):  
O.M. Momoh ◽  
S.T. Vincent ◽  
A. Yakubu
Keyword(s):  
Positive Selection ◽  
Protein Function ◽  
In Silico ◽  
Mammalian Species ◽  
Substitution Matrix ◽  
Sequence Evolution ◽  
Synonymous Mutations ◽  
Allelic Sequence ◽  
Extant Species ◽  
Beta Lactoglobulin

This study investigated in silico, the genetic diversity of Beta- Lactoglobulin (?-Lg) and their evolutionary and differentiation within and among selected mammalian species; and also examined the attendant effects of polymorphism on the functionality of the gene. A total of 21 ?-Lg gene sequences with corresponding amino acids belonging to 6 species [cattle (4), buffalo (4), sheep (3), goat (3), pig (3) and horse (4)] were retrieved from GenBank (www.ncbi.nlm.nih.gov). All sequences were trimmed to equal length (500bp) corresponding to the same region. Sequences? alignment, translation and comparison were done with ClustalW using IUB substitution matrix, gap open penalty of 15 and gap extension penalty of 6.66. The alignment revealed high polymorphism of sequences among extant species. The Dxy inferred using pdistance revealed that sheep and goat had the lowest distance of 0.05 with a maximum distance of 0.65 between goat and horse. The hypothesis of strict neutrality (dN = dS) was rejected for all extant species as allelic sequence evolution was driven by both purifying and positive selection. Only those of pig and buffalo were driven by positive selection. In-silico functional analysis of non-synonymous mutations using PANTHER revealed that, all the 12 amino acid substitutions (10 in cattle and 2 in sheep) did not impair protein function. The Neighbour-Joining phylogeny revealed trans-species evolution, but a species-wise phylogeny was obtained for UPGMA with consensus sequences. Thus, all probed SNPs from this study have no deleterious effect and can be tolerated by breeders when selecting stocks for milk improvement.

scholarly journals Identification of residue inversions in large phylogenies of duplicated proteins

2021 ◽  
Author(s):  
Stefano Pascarelli ◽  
Paola Laurino
Keyword(s):  
Gene Duplication ◽  
Protein Sequence ◽  
Protein Function ◽  
High Throughput Sequencing ◽  
Functional Divergence ◽  
Growth Factor Receptor ◽  
Sequence Evolution ◽  
Protein Database ◽  
Sequencing Studies ◽  
Homology Relationship

Connecting protein sequence to function is becoming increasingly relevant since high-throughput sequencing studies accumulate large amounts of genomic data. Protein database annotation helps to bridge this gap; however, it is fundamental to understand the mechanisms underlying functional inheritance and divergence. If the homology relationship between proteins is known, can we determine whether the function diverged? In this work, we analyze different possibilities of protein sequence evolution after gene duplication and identify "residue inversions", i.e., sites where the relationship between the ancestry and the functional signal is decoupled. Residues in these sites play a role in functional divergence and could indicate a shift in protein function. We develop a method to recognize residue inversions in a phylogeny and test it on real and simulated datasets. In a dataset built from the Epidermal Growth Factor Receptor (EGFR) sequences found in 88 fish species, we identify 19 positions that went through inversion after gene duplication, mostly located at the ligand-binding extracellular domain.

scholarly journals Genetic Diversity and Natural Selection of Plasmodium vivax Duffy Binding Protein-II From China-Myanmar Border of Yunnan Province, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Tian-Qi Shi ◽  
Hai-Mo Shen ◽  
Shen-Bo Chen ◽  
Kokouvi Kassegne ◽  
Yan-Bing Cui ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Natural Selection ◽  
Genetic Differentiation ◽  
Positive Selection ◽  
Plasmodium Vivax ◽  
Yunnan Province ◽  
Duffy Binding Protein ◽  
Synonymous Mutations ◽  
Selection Of

Malaria incidence has declined dramatically over the past decade and China was certified malaria-free in 2021. However, the presence of malaria in border areas and the importation of cases of malaria parasites are major challenges for the consolidation of the achievements made by China. Plasmodium vivax Duffy binding protein (PvDBP) performs a significant role in erythrocyte invasion, and is considered a promising P. vivax vaccine. However, the highly polymorphic region of PvDBP (PvDBP-II) impedes the development of blood-stage vaccine against P. vivax. In this study, we investigated the genetic diversity and natural selection of PvDBP-II among 124 P. vivax isolates collected from the China-Myanmar border (CMB) in Yunnan Province, China, during 2009–2011. To compare genetic diversity, natural selection, and population structure with CMB isolates, 85 pvdbp-II sequences of eastern Myanmar isolates were obtained from GenBank. In addition, global sequences of pvdbp-II were retrieved from GenBank to establish genetic differentiation relationships and networks with the CMB isolates. In total, 22 single nucleotide polymorphisms reflected in 20 non-synonymous and two synonymous mutations were identified. The overall nucleotide diversity of PvDBP-II from the 124 CMB isolates was 0.0059 with 21 haplotypes identified (Hd = 0.91). The high ratio of non-synonymous to synonymous mutations suggests that PvDBP-II had evolved under positive selection. Population structure analysis of the CMB and eastern Myanmar isolates were optimally grouped into five sub-populations (K = 5). Polymorphisms of PvDBP-II display that CMB isolates were genetically diverse. Mutation, recombination, and positive selection promote polymorphism of PvDBP-II of P. vivax population. Although low-level genetic differentiation in eastern Myanmar was identified along with the more effective malaria control measures, the complexity of population structure in malaria parasites has maintained. In conclusion, findings from this study advance knowledge of the understanding of the dynamic of P. vivax population, which will contribute to guiding the rational design of a PvDBP-II based vaccine.

scholarly journals IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

2020 ◽  
Author(s):  
Oladoja AWofisayo
Keyword(s):  
Comparative Genomics ◽  
Peer Review ◽  
In Silico ◽  
Drug Targets ◽  
Homo Sapiens ◽  
Mammalian Species ◽  
Target Selection ◽  
Plasmodium Species ◽  
Data Bank ◽  
Sequence Motifs

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols. Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS

scholarly journals Positive Selection on Two Mitochondrial Coding Genes and Adaptation Signals in Hares (Genus Lepus) from China

2020 ◽  
Author(s):  
Asma Awadi ◽  
Hichem Ben Slimen ◽  
Helmut Schaschl ◽  
Felix Knauer ◽  
Franz Suchentrunk
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Protein Function ◽  
Transmembrane Domain ◽  
Proton Translocation ◽  
Introgressive Hybridization ◽  
Vibrational Entropy ◽  
Mutant Type ◽  
Selection For ◽  
Protein Variants

Abstract Background: Animal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway. Recent studies of selection on different mitochondrial OXPHOS genes have revealed the adaptive implications of amino acid changes in these subunits. In hares, climatic variation and/or introgression were suggested to be at the origin of such adaptation. Here we looked for evidence of positive selection in three mitochondrial OXPHOS genes, using tests of selection, protein structure modelling and effects of amino acid substitutions on the protein function and stability. We also used statistical models to test for climate and introgression effects on sites under positive selection. Results: Our results revealed seven sites under positive selection in ND4 and three sites in Cytb. However, no sites under positive selection were observed in the COX1 gene. All three subunits presented a high number of codons under negative selection. Sites under positive selection were mapped on the tridimensional structure of the predicted models for the respective mitochondrial subunit. Of the ten amino acid replacements inferred to have evolved under positive selection for both subunits, six were located in the transmembrane domain. On the other hand, three codons were identified as sites lining proton translocation channels. Furthermore, four codons were identified as destabilizing with a significant variation of Δ vibrational entropy energy between wild and mutant type. Moreover, the PROVEAN analysis suggested that among all positively selected sites two fixed amino acid replacements altered the protein functioning. The statistical model runs indicated significant effects of climate on the presence of ND4 and Cytb protein variants, but no effect by trans-specific mitochondrial DNA introgresson.Conclusions: Positive selection was observed in several codons in two OXPHOS genes. We found that substitutions in the positively selected codons have structural and functional impacts on the encoded proteins. Our results are concordantly suggesting that adaptations have strongly affected the evolution of mtDNA of hare species with potential effects on the protein function. Environmental/climatic changes appear to be a major trigger of this adaptation, whereas trans-specific introgressive hybridization seems to play no major role for the occurrence of protein variants.

scholarly journals Intrinsically disordered regions are abundant in simplexvirus proteomes and display signatures of positive selection

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Alessandra Mozzi ◽  
Diego Forni ◽  
Rachele Cagliani ◽  
Mario Clerici ◽  
Uberto Pozzoli ◽  
...  
Keyword(s):  
Positive Selection ◽  
Protein Function ◽  
Three Dimensional ◽  
New Host ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Human Proteins ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Disordered Regions

Abstract Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus Simplexvirus) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans. We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events that drove herpesvirus adaptation to a new host. We show that HSV-2 intrinsically disordered regions (IDRs)—that is, protein domains that do not adopt compact three-dimensional structures—are strongly enriched in positive selection signals. Analysis of viral proteomes indicated that a significantly higher portion of simplexvirus proteins is disordered compared with the proteins of other human herpesviruses. IDR abundance in simplexvirus proteomes was not a consequence of the base composition of their genomes (high G + C content). Conversely, protein function determines the IDR fraction, which is significantly higher in viral proteins that interact with human factors. We also found that the average extent of disorder in herpesvirus proteins tends to parallel that of their human interactors. These data suggest that viruses that interact with fast-evolving, disordered human proteins, in turn, evolve disordered viral interactors poised for innovation. We propose that the high IDR fraction present in simplexvirus proteomes contributes to their wider host range compared with other herpesviruses.

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