scholarly journals Genetic polymorphism of the extracellular region in surface associated interspersed 1.1 gene of Plasmodium falciparum field isolates from Thailand

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Natpasit Chaianantakul ◽  
Tippawan Sungkapong ◽  
Jirapinya Changpad ◽  
Keawalin Thongma ◽  
Sasiwimon Sim-ut ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dna Sequences ◽  
Balancing Selection ◽  
Haplotype Diversity ◽  
Research Area ◽  
Terminal Region ◽  
Common Amino Acid ◽  
Rich Domain ◽  
Extracellular Region ◽  
Variable Surface

Abstract Background A novel variable surface antigens (VSAs), Surface-associated interspersed proteins (SUFRINs), is a protein that is modified on the surface of infected red blood cell (iRBC). Modified proteins on the iRBC surface cause severe malaria, which can lead to death throughout the life cycle of a malaria parasite. Previous study suggested that SURFIN1.1 is an immunogenic membrane-associated protein which was encoded by using the surf1.1 gene expressed during the trophozoite and schizont stages. This study aimed to identify the regions of SURFIN1.1 and investigate the genetic diversity of the extracellular region of the surf1.1 gene. Methods A total of 32 blood samples from falciparum malaria cases that were diagnosed in Si Sa Ket Province, Thailand were collected. Plasmodium genomic DNA was extracted, and the extracellular region of surf1.1 gene was amplified using the polymerase chain reaction (PCR). A sequence analysis was then performed to obtain the number of haplotypes (H), the haplotype diversity (Hd), and the segregating sites (S), while the average number of nucleotide differences between two sequences (Pi); in addition, neutrality testing, Tajima’s D test, Fu and Li’s D* and F* statistics was also performed. Results From a total of 32 patient-isolated samples, 31 DNA sequences were obtained and analysed for surf1.1 gene extracellular region polymorphism. Researchers observed six distinct haplotypes in the current research area. Haplotype frequencies were 61.3%, 16.2%, and 12.9% for H1, H2, and H3, respectively. The remaining haplotype (H4-H6) frequency was 3.2% for each haplotype. Hd was 0.598 ± 0.089 with the Pi of 0.00381, and S was 15. The most common amino acid polymorphic site was E251Q; other sites included N48D, I49V, E228D, E235S, L265F, K267T, E276Q, and S288F. Fu and Li’s D* test value was − 1.24255, Fu and Li’s F* test value was − 1.10175, indicating a tendency toward negative balancing selection acting on the surf1.1 N-terminal region. The most polymorphic region was variable 2 (Var2) while cysteine-rich domain (CRD) was conserved in both the amino acid and nucleotide extracellular region of surf1.1 gene. Conclusions The Thai surf1.1 N-terminal region was well-conserved with only a few polymorphic sites remaining. In this study, the data regarding current bearing on the polymorphism of extracellular region of surf1.1 gene were reported, which might impact the biological roles of P. falciparum. In addition, may possibly serve as a suitable candidate for future development of SURFIN-based vaccines regarding malaria control. Graphic abstract

scholarly journals Molecular Characterization of Mycoplasma arthritidis Variable Surface Protein MAA2

1998 ◽  
Vol 66 (6) ◽  
pp. 2576-2586 ◽  
Author(s):  
Leigh Rice Washburn ◽  
Keith E. Weaver ◽  
Elizabeth J. Weaver ◽  
Wendy Donelan ◽  
Suhaila Al-Sheboul
Keyword(s):  
Amino Acid ◽  
Signal Peptide ◽  
Dna Sequences ◽  
Surface Protein ◽  
Carboxypeptidase Y ◽  
Coding Region ◽  
Intact Cells ◽  
Mycoplasma Arthritidis ◽  
E Coli ◽  
Variable Surface

Earlier studies implied a role for Mycoplasma arthritidis surface protein MAA2 in cytadherence and virulence and showed that it exhibited both size and phase variability. Here we report the further analysis of MAA2 and the cloning and sequencing of the maa2 gene from two M. arthritidis strains, 158p10p9 and H606, expressing two size variants of MAA2. Triton X-114 partitioning and metabolic labeling with [3H]palmitic acid suggested lipid modification of MAA2. Surface exposure of the C terminus was indicated by cleavage of monoclonal antibody-specific epitopes from intact cells by carboxypeptidase Y. The maa2genes from both strains were highly conserved, consisting largely of six (for 158p10p9) or five (for H606) nearly identical, 264-bp tandem direct repeats. The deduced amino acid sequence predicted a largely hydrophilic, highly basic protein with a 29-amino-acid lipoprotein signal peptide. The maa2 gene was expressed inEscherichia coli from the lacZ promoter of vector pGEM-T. The recombinant product was approximately 3 kDa larger than the native protein, suggesting that the signal peptide was not processed in E. coli. The maa2 gene and upstream DNA sequences were cloned from M. arthritidisclonal variants differing in MAA2 expression state. Expression state correlated with the length of a poly(T) tract just upstream of a putative −10 box. Full-sized recombinant MAA2 was expressed inE. coli from genes derived from both ON and OFF expression variants, indicating that control of expression did not include alterations within the coding region.

scholarly journals Bitter taste perception in Neanderthals through the analysis of the TAS2R38 gene

2009 ◽  
Vol 5 (6) ◽  
pp. 809-811 ◽  
Author(s):  
Carles Lalueza-Fox ◽  
Elena Gigli ◽  
Marco de la Rasilla ◽  
Javier Fortea ◽  
Antonio Rosas
Keyword(s):  
Amino Acid ◽  
Bitter Taste ◽  
Balancing Selection ◽  
Major Effect ◽  
Taste Perception ◽  
Toxic Substances ◽  
Modern Humans ◽  
Common Amino Acid ◽  
Tas2r38 Gene

The bitter taste perception (associated with the ability or inability to taste phenylthiocarbamide) is mediated by the TAS2R38 gene. Most of the variation in this gene is explained by three common amino-acid polymorphisms at positions 49 (encoding proline or alanine), 262 (alanine or valine) and 296 (valine or isoleucine) that determine two common isoforms: proline–alanine–valine (PAV) and alanine–valine–isoleucine (AVI). PAV is the major taster haplotype (heterozygote and homozygote) and AVI is the major non-taster haplotype (homozygote). Amino acid 49 has the major effect on the distinction between tasters and non-tasters of all three variants. The sense of bitter taste protects us from ingesting toxic substances, present in some vegetables, that can affect the thyroid when ingested in large quantities. Balancing selection has been used to explain the current high non-taster frequency, by maintaining divergent TAS2R38 alleles in humans. We have amplified and sequenced the TAS2R38 amino acid 49 in the virtually uncontaminated Neanderthal sample of El Sidrón 1253 and have determined that it was heterozygous. Thus, this Neanderthal was a taster individual, although probably slightly less than a PAV homozygote. This indicates that variation in bitter taste perception pre-dates the divergence of the lineages leading to Neanderthals and modern humans.

scholarly journals Haplotype Diversity at the Pi-ta Locus in Cultivated Rice and Its Wild Relatives

2008 ◽  
Vol 98 (12) ◽  
pp. 1305-1311 ◽  
Author(s):  
X. Wang ◽  
Y. Jia ◽  
Q. Y. Shu ◽  
D. Wu
Keyword(s):  
Dna Sequences ◽  
Haplotype Diversity ◽  
Polymerase Chain Reaction Analysis ◽  
Single Amino Acid ◽  
Receptor Protein ◽  
Coding Region ◽  
Cultivated Rice ◽  
Genome Species ◽  
Rich Domain ◽  
Resistance Specificity

The Pi-ta gene in rice confers resistance to races of Magnaporthe oryzae that contain AVR-Pita. Pi-ta encodes a predicted cytoplasmic receptor protein with a nucleotide-binding site and a leucine-rich domain. A panel of 51 Oryza accessions of AA genome species Oryza sativa, O. glaberrima, O. rufipogon, O. nivara, and O. barthii, and CC genome species O. officinalis were sequenced to investigate the diversity present in the exon and intron regions of the Pi-ta gene. Two major clades were identified, consisting of 16 different sequences with numerous insertion and deletions. Only one Pi-ta resistance allele was identified despite DNA sequences revealing 16 Pi-ta variants. Most differences were identified in the intron region, and obvious selection of any motif was not observed in the coding region of Pi-ta variants. Reverse-transcription polymerase chain reaction analysis of seedlings revealed that all Pi-ta variants were expressed with or without pathogen inoculation. The 15 Pi-ta variants can be translated into nine proteins highly similar to the Pi-ta protein. Resistance to M. oryzae expressing AVR-Pita correlates with alanine and susceptibility correlates with serine at position 918 of Pi-ta in most accessions examined. These data confirm that a single amino acid controlling resistance specificity underlies the evolution of resistance of Pi-ta genes in rice.

scholarly journals cDNA Cloning, Sequence Analysis of the Porcine LIM and Cysteine-rich Domain 1 Gene

2005 ◽  
Vol 37 (12) ◽  
pp. 843-850 ◽  
Author(s):  
Jun Wang ◽  
Chang-Yan Deng ◽  
Yuan-Zhu Xiong ◽  
Bo Zuo ◽  
Lei Xing ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Fate ◽  
Phosphorylation Site ◽  
Amino Acid Sequences ◽  
Terminal Region ◽  
Polymorphism Analysis ◽  
Phosphorylation Sites ◽  
Lim Domain ◽  
Rich Domain ◽  
Cysteine Rich Domain

AbstractLIM domain proteins are important regulators in cell growth, cell fate determination, cell differentiation and remodeling of the cell cytoskeleton by their interaction with various structural proteins, kinases and transcriptional regulators. Using molecular biology combined with in silico cloning, we have cloned the complete coding sequence of pig LIM and the cysteine-rich domain 1 gene (LMCD1) which encodes a 363 amino acid protein. The estimated molecular weight of the LMCD1 protein is 40,788 Da with a pI of 8.39. It was found to be highly expressed in both skeletal muscle and cardiac muscle. Alignment analysis revealed that the deduced protein sequence shares 86%, 91% and 93% homology with that of its human, mouse and rat counterparts, respectively. The LMCD1 protein was predicted by bioinformatics software to contain a novel cysteine-rich domain in the N-terminal region, two LIM domains in the C-terminal region, nine potential protein kinase C phosphorylation sites, seven casein kinase II phosphorylation sites, a tyrosine kinase phosphorylation site, seven N-glycosylation and N-myristoylation sites and a single potential N-glycosylation site, which is similar to the protein's human counterpart. Phylogenetic tree was constructed by aligning the amino acid sequences of the LIM domain from different species. In addition, four base mutations were detected by comparing the sequences of Large White pigs with those of Chinese Meishan pigs. The G294A mutation site was confirmed by polymerase chain reaction-single-strand conformation polymorphism analysis. Its allele frequencies were studied in five pig breeds.

scholarly journals HLA-DRB1 Alleles Associated with Lower Leishmaniasis Susceptibility Share Common Amino Acid Polymorphisms and Epitope Binding Repertoires

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 270
Author(s):  
Nicky de Vrij ◽  
Pieter Meysman ◽  
Sofie Gielis ◽  
Wim Adriaensen ◽  
Kris Laukens ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Leishmania Species ◽  
Hla Polymorphism ◽  
Common Amino Acid ◽  
Binding Core ◽  
Epitope Discovery ◽  
Epitope Binding ◽  
The Impact

Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.

scholarly journals Comprehensive transcriptome and metabolome profiling reveal metabolic mechanisms of Nitraria sibirica Pall. to salt stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huanyong Li ◽  
Xiaoqian Tang ◽  
Xiuyan Yang ◽  
Huaxin Zhang
Keyword(s):  
Salt Stress ◽  
Amino Acid ◽  
Salt Tolerance ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sulfur Metabolism ◽  
Enrichment Analysis ◽  
Extracellular Region ◽  
Nitraria Sibirica

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

scholarly journals Evidence for Selection at the fused1 Locus of Drosophila americana

Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 279-290 ◽  
Author(s):  
Jorge Vieira ◽  
Bryant F McAllister ◽  
Brian Charlesworth
Keyword(s):  
Amino Acid ◽  
Sequence Variation ◽  
Amino Acid Replacement ◽  
Population Subdivision ◽  
Amino Acid Substitutions ◽  
Clinal Variation ◽  
Haplotype Structure ◽  
Common Amino Acid ◽  
Chromosome Arrangement ◽  
Dna Sequence Variation

Abstract We analyze genetic variation at fused1, a locus that is close to the centromere of the X chromosome-autosome (X/4) fusion in Drosophila americana. In contrast to other X-linked and autosomal genes, for which a lack of population subdivision in D. americana has been observed at the DNA level, we find strong haplotype structure associated with the alternative chromosomal arrangements. There are several derived fixed differences at fused1 (including one amino acid replacement) between two haplotype classes of this locus. From these results, we obtain an estimate of an age of ∼0.61 million years for the origin of the two haplotypes of the fused1 gene. Haplotypes associated with the X/4 fusion have less DNA sequence variation at fused1 than haplotypes associated with the ancestral chromosome arrangement. The X/4 haplotypes also exhibit clinal variation for the allele frequencies of the three most common amino acid replacement polymorphisms, but not for adjacent silent polymorphisms. These patterns of variation are best explained as a result of selection acting on amino acid substitutions, with geographic variation in selection pressures.

scholarly journals Plasmodium vivax Cysteine-Rich Protective Antigen Polymorphism at Exon-1 Shows Recombination and Signatures of Balancing Selection

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 29
Author(s):  
Lilia González-Cerón ◽  
José Cebrián-Carmona ◽  
Concepción M. Mesa-Valle ◽  
Federico García-Maroto ◽  
Frida Santillán-Valenzuela ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Plasmodium Vivax ◽  
Nucleotide Diversity ◽  
Protective Antigen ◽  
Balancing Selection ◽  
Southern Mexico ◽  
Exon 2 ◽  
Exon 1 ◽  
Tajima’S D

Plasmodium vivax Cysteine-Rich Protective Antigen (CyRPA) is a merozoite protein participating in the parasite invasion of human reticulocytes. During natural P. vivax infection, antibody responses against PvCyRPA have been detected. In children, low anti-CyRPA antibody titers correlated with clinical protection, which suggests this protein as a potential vaccine candidate. This work analyzed the genetic and amino acid diversity of pvcyrpa in Mexican and global parasites. Consensus coding sequences of pvcyrpa were obtained from seven isolates. Other sequences were extracted from a repository. Maximum likelihood phylogenetic trees, genetic diversity parameters, linkage disequilibrium (LD), and neutrality tests were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. In 22 sequences from Southern Mexico, two synonymous and 21 nonsynonymous mutations defined nine private haplotypes. These parasites had the highest LD-R2 index and the lowest nucleotide diversity compared to isolates from South America or Asia. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity and Rm values than those of exon-2. Exon-1 had significant positive values for Tajima’s D, β-α values, and for the Z (HA: dN > dS) and MK tests. These patterns were similar for parasites of different origin. The polymorphic amino acid residues at PvCyRPA resembled the conformational B-cell peptides reported in PfCyRPA. Diversity at pvcyrpa exon-1 is caused by mutation and recombination. This seems to be maintained by balancing selection, likely due to selective immune pressure, all of which merit further study.

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