Linkages between blood groups and malaria susceptibility

Blood typing has revolutionized the field of medical science since its discovery about a century ago. Besides its established role in life-saving blood transfusions, researchers have always been curious about the relationship between blood groups and human ailments. The effect of blood groups on disease outcomes, susceptibility, and mortality has been widely explored. According to a particular school of thought, the endemicity of diseases shapes the distribution of blood group frequency in human populations and exert selection pressure favoring one blood type over another. Here we discuss the scope and association of different blood groups in the context of malaria.

Variability of the EG95 antigen-coding gene of Echinococcus granulosus in animal and human origin: implications for vaccine development

In the present study, the genetic variability of the EG95 protein-coding gene in several animal and human isolates of Echinococcus granulosus was investigated. A total of 24 isolates collected from cattle, buffalo, sheep, goat, dog and man were amplified by Eg95-coding gene-specific primers. From the generated sequence information, a conceptual amino acid sequence was deduced. Phylogenetically, the Eg95 coding gene belongs to the Eg95-1/Eg95-2/Eg95-3/Eg95-4 cluster. Further confirmation on the maximum composite likelihood analysis revealed that the overall transition/transversion bias was 2.913. This finding indicated thatthere is bias towards transitional and transversional substitution. Using artificial neural networks, a B-cell epitope was predicted on primary sequence information. Stretches of amino acid residues varied between animal and human isolates when hydrophobicity was considered. Flexibility also varied between larval and adult stages of the organism. This observation is important to develop vaccines. However, cytotoxic T-lymphocyte epitopes on primary sequence data remained constant in all isolates. In this study, agretope identification started with hydrophobic amino acids. Amino acids with the same physico-chemical properties were present in the middle. The conformational propensity of the Eg95-coding gene of 156 amino acid residues had α-turns and β-turns, and α-amphipathic regions up to 129, 138–156 and 151–155 residues, respectively. The results indicated potential T-cell antigenic sites. The overall Tajima’s D value was negative (−2.404165), indicative of negative selection pressure.

Insights into the evolution of extracellular leucine-rich repeats in metazoans with special reference to Toll-like receptor 4

The importance of the widely spread leucine-rich repeat (LRR) motif was studied considering TLRs, the LRR-containingprotein involved in animal immune response. The protein connects intracellular signalling with a chain of molecularinteractions through the presence of LRRs in the ectodomain and TIR in the endodomain. Domain analyses with humanTLR1-9 reported ectodomain with tandem repeats, transmembrane domain and TIR domain. The repeat number variedacross members of TLR and remained characteristic to a particular member. Analysis of gene structure revealed absence ofcodon interruption with TLR3 and TLR4 as exceptions. Extensive study with TLR4 from metazoans confirmed thepresence of 23 LRRs in tandem. Distinct clade formation using coding and amino acid sequence of individual repeatsillustrated independent evolution. Although ectodomain and endodomain exhibited differential selection pressure, withinthe ectodomain, however, the individual repeats displayed positive, negative and neutral selection pressure depending ontheir structural and functional significance.

Identifying signatures of recent selection in Holstein cattle in the Tropic / Identificación de señales de selección reciente en ganado Holstein en el trópico / Identificação de sinais de seleção recente no gado Holandês no trópico

Abstract Background: Holstein cattle have undergone strong selection processes in the world. These selection signatures can be recognized and utilized to identify regions of the genome that are important for milk yield. Objective: To identify recent selection signatures in Holstein from the Province of Antioquia (Colombia), using the integrated haplotype score (iHS) methodology. Methods: Blood or semen was extracted from 150 animals with a commercial kit. The animals were genotyped with the BovineLD chip (6909 SNPs). The editing process was carried out while preserving the loci whose minor allele frequency (MAF) was greater than 0.05. In addition, genotypes with Mendelian errors were discarded using R and PLINK v1.07 software programs. Furthermore, the extended haplotype homozygosity (EHH), iHS and the p-value were determined with the "rehh" package of R language. Results: The minor allele frequencies showed a tendency toward intermediate frequency alleles. In total, 144 focal markers were significant (p<0.001) for selection signatures. Some chromosomes showed a greater number of signatures than others. Many of the variants were found inside genes, although they were in intronic regions. Some important regions were associated with genes TRAPPC12, PANK3, ZNF16, OPLA and DPYSL4, which are related with cellular transport, excretion or metabolism. Conclusion: Identifying signatures of selection using the iHS method made it possible to determine some important regions for selection in Holstein cattle in the high tropics, some of which had been previously reported to be associated with quantitative traits loci (QTLs).

Resumen Antecedentes: El ganado Holstein ha sido sometido a procesos fuertes de selección en el mundo. Estas señales de selección pueden ser reconocidas y utilizadas para identificar regiones del genoma importantes para la producción de leche. Objetivo: Identificar señales de selección recientes en ganado Holstein de la Provincia de Antioquia (Colombia), mediante la metodología de puntaje haplotípico integrado (iHS). Métodos: A 150 animales se les extrajo DNA de sangre o semen mediante un kit comercial y posteriormente se genotiparon los animales con el chip BovineLD (6909 SNPs). Se realizó edición conservando los loci con frecuencia del alelo menor (MAF) superior a 0,05. Además, se descartaron los genotipos con errores mendelianos, usando el software R y PLINK v1.07. La determinación de la homocigosidad haplotípica extendida (EHH), iHS y el valor p se realizó utilizando el paquete "rehh" de R. Resultados: Las frecuencias del alelo menor mostraron una tendencia hacia alelos de frecuencias intermedias. En total, 144 marcadores focales fueron significativos (p<0,001) para las señales de selección. Algunos cromosomas presentaron mayor número de señales de selección que otros. Muchas de las variantes focales se encontraron al interior de genes, aunque comúnmente en regiones intrónicas. Algunas de las regiones importantes estuvieron asociadas con genes como TRAPPC12, PANK3, ZNF16, OPLA y DPYSL4 que en general se encuentran asociados con funciones relacionadas con el transporte, excreción o metabolismo celular. Conclusión: La identificación de señales de selección usando el método iHS permitió determinar algunas regiones importantes para la selección en ganado Holstein del trópico alto, algunas de las cuales han sido previamente reportadas por su asociación a loci de características cuantitativas (QTLs).

Resumo Antecedentes: O gado holandês tem sido objeto de processos de seleção fortes no mundo. Estes sinais de seleção podem ser reconhecidos e utilizados para identificar regiões do genoma importantes para a produção de leite. Objetivo: Identificar sinais de seleção recente em gado Holandês de la Província de Antioquia (Colômbia), através da metodologia de pontuação haplotípica integrada (iHS). Métodos: Foram usados 150 animais para a extração de DNA a partir de sangre ou sêmen usando kit comercial, os animais foram posteriormente genotipados com o chip BovineLD (6909 SNPs). A edição foi feita mantendo os loci com frequência do alelo menor (MAF) de 0,05; além disso, genótipos com erros mendelianos foram descartados usando o programa R e PLINK v1.07. A determinação da homozigosidade haplotípica estendida (EHH), iHS e valor p foi realizada utilizando o pacote estatístico R "reeh". Resultados: As frequências do alelo menor mostraram uma tendência inclinada a frequências intermédias. No total, 144 marcadores focais foram significativos (p<0,001) para os sinais de seleção. Alguns cromossomos apresentaram mais numero de sinais de seleção que outros. Muitas dos variantes focais foram encontradas dentro dos genes, embora comumente em regiões intrônicas. Algumas das regiões importantes foram associadas com genes como TRAPPC12, PANK3, ZNF16, OPLA e DPYSL4 que geralmente estão associadas a funções relacionadas com o transporte, a excreção ou metabolismo celular. Conclusão: A identificação de sinais de seleção usando o método iHS permitiu determinar algumas regiões importantes para a seleção no gado holandês do tropico alto, algumas destas regiões foram previamente relatados por sua associação com loci de características quantitativas (QTLs).

ESTABLECIMIENTO DE UN SISTEMA DE SELECCIÓN IN VITRO DE VARIEDADES VENEZOLANAS DE ARROZ (Oryza sativa L.) RESISTENTES AL HONGO Pyricularia grisea / Establishment of an in vitro Selection of Venezuelan Cultivars of Rice (Oryza sativa L.) Resistant to the Fungus Pyricularia grisea

RESUMEN. El arroz, luego del trigo, es el cereal más importante del mundo, sin embargo, es susceptible al ataque de numerosos patógenos, siendo Pyricularia grisea, el más dañino. Este trabajo estableció un sistema de selección in vitro de variedades venezolanas a P. grisea, optimizando el sistema de regeneración por embriogénesis somática (inducción, regeneración y estrés por desecación), sometiendo el callo embriogénico (E) a presión de selección del filtrado crudo "FC" a través de cambios a la misma concentración "MC" o por incrementos progresivos en la concentración "IPC", obteniendo plantas tolerantes al fitopatógeno. El máximo porcentaje de inducción de callo embriogénico oscilo entre 30-65 %, en las cuatro variedades (Araure-4 y Venezuela 21: 1 mg.L-1 + 2 mg.L-1 K; Cimarrón: 3 mg.L-1 + 2 mg.L-1 K; Centauro: 1 mg.L-1 + 2 mg.L-1 BAP), mientras que la regeneración estuvo entre 44 y 52 % con 0.5 mg.L-1 + 2 mg.L-1 BAP a 48 h de desecación para Centauro y 24 h para las otras tres variedades. La frecuencia regenerativa de los callos E disminuyo a medida que se incrementó la concentración del FC, independientemente del método de presión selectiva. El promedio de plantas diferenciada por variedad, dependió del método de presión usado, siendo el sistema IPC (25 % para Centauro y 50 % para las otras tres variedades) el que mostro los resultados más favorables, evidenciándose que para las condiciones de los sistemas selectivos de FC evaluados, la resistencia expresada a nivel de planta in vivo no corresponde a la encontrada in vitro.

ABSTRACT. Rice after wheat is the most important cereal in the world, however, it is susceptible to attack by many pathogens, which Pyricularia grisea being the most harmful. In the current study we established an in-vitro selection system of P. grisea on Venezuelan rice varieties. A somatic embryogenesis regeneration system was optimized (induction, regeneration and desiccation) to expose embryogenic callus (E) to crude filtrate "CF" selection pressure through changes at the same concentration "SC" or progressive concentration increments " PIC "of P. grisea, and thus obtain plants tolerant to the pathogen. The maximum percentage of embryogenic callus induction ranged between 30-65 % in the four varieties (Araure-4 and Venezuela- 21: 1 mg.L-1 + 2 mg.L-1 K; Cimarron: 3 mg.L-1 mg.L-1 + 2 K; Centauro: 1 mg.L-1 + 2 mg.L-1 BAP) while regeneration was between 44 and 52 % with 0.5 mg.L-1 + 2 mg.L- 1 BAP 48 h of desiccation for Centauro and 24 h for the other three varieties. The regeneration frequency of embryogenic callus decreased as the concentration of FC increased, regardless of the method of selective pressure. The average differentiated plants per variety, depended on the pressure method used, with the PIC system being the most favorable (25 % for Centauro and 50 % for the other three varieties). The result demonstrated, to resistance expressed for plants in vivo does not correspond to the in vitro conditions

Codon Usage Patterns of Tyrosinase Genes in Clonorchis sinensis

Codon usage bias (CUB) is a unique property of genomes and has contributed to the better understanding of the molecular features and the evolution processes of particular gene. In this study, genetic indices associated with CUB, including relative synonymous codon usage and effective numbers of codons, as well as the nucleotide composition, were investigated in the Clonorchis sinensis tyrosinase genes and their platyhelminth orthologs, which play an important role in the eggshell formation. The relative synonymous codon usage patterns substantially differed among tyrosinase genes examined. In a neutrality analysis, the correlation between GC₁₂ and GC₃ was statistically significant, and the regression line had a relatively gradual slope (0.218). NC-plot, i.e., GC₃ vs effective number of codons (ENC), showed that most of the tyrosinase genes were below the expected curve. The codon adaptation index (CAI) values of the platyhelminth tyrosinases had a narrow distribution between 0.685/0.714 and 0.797/0.837, and were negatively correlated with their ENC. Taken together, these results suggested that CUB in the tyrosinase genes seemed to be basically governed by selection pressures rather than mutational bias, although the latter factor provided an additional force in shaping CUB of the C. sinensis and Opisthorchis viverrini genes. It was also apparent that the equilibrium point between selection pressure and mutational bias is much more inclined to selection pressure in highly expressed C. sinensis genes, than in poorly expressed genes.

Serotypes of HFMD-associated HEV-B species and genetic characteristics of the VP1 gene in coxsack-ievirus B2 and B5 strains isolated in Anyang area from 2011 to 2015 / 中华微生物学和免疫学杂志

Objective To investigate the serotypes of human enterovirus B ( HEV-B) species cau-sing hand, foot and mouth disease ( HFMD) and to analyze the genetic characteristics of VP1 region in cox-sackievirus B2 ( CVB2 ) and coxsackievirus B5 ( CVB5 ) strains circulating in Anyang area during 2011 to 2015. Methods Real-time RT-PCR and semi-nested RT-PCR were performed to identify coxsackievirus A16 (CVA16), enterovirus 71 (EV71) and other serotypes of enterovirus in order to obtain the complete etiologic composition of HFMD. The numbers of HEV-B serotypes and the percentages of specimens positive for every serotype in all enterovirus-positive specimens were calculated. As CVB2 and CVB5 were the pre-dominant serotypes of HEV-B species, five pairs of primers targeting the VP1 regions of CVB2 and CVB5 were designed to obtain the complete nucleotide sequences of CVB2 and CVB5 VP1 regions. The phylogenet-ic trees were constructed based on the VP1 sequences obtained in this study and those submitted to GenBank by using MEGA7. 0 and BioEdit7. 2. The selection pressures on VP1 regions of CVB2 and CVB5 strains cir-culating in China in recent years were evaluated with the online program of DataMonkey. Results A total of 57 specimens that belonged to 14 serotypes of HEV-B species were detected in Anyang area from 2011 to 2015. The 14 serotypes of HEV-B species accounted for 56% of all serotypes of enterovirus and the speci-mens positive for HEV-B species accounted for 3. 06% of all enterovirus-positive specimens. The HFMD ca-ses caused by most of the HEV-B serotypes were sporadic cases. Small outbreaks of HFMD could also be caused by some serotypes of HEV-B such as CVB2 and CVB5. The complete sequences of VP1 region were obtained from 8 CVB2 strains and 9 CVB5 strains. The phylogenetic trees based on the VP1 sequences dem-onstrated that the CVB2 strains were classified into four genotypes ( A-D) . The mean evolutionary distances between different genotypes ranged from 0. 191 to 0. 208 and the similarities in nucleotide sequences ranged from 79. 7% to 85. 8%. The CVB5 strains were classified into 6 genotypes (A-F). The mean evolutionary distances and the similarities in nucleotide sequences between different genotypes of CVB5 strains ranged from 0. 170 to 0. 285 and 76. 0% to 86. 8%, respectively. Strains of different genotypes varied significantly in the residues on positons 157 and 263 in the VP1 region of CVB2 strains and on positions 75, 90 and 95 in the VP1 region of CVB5 strains. All of the CVB2 strains isolated in Anyang area belonged to D genotype and located intensively in one lineage. The CVB5 strains circulated in Anyang area belonged to F genotype and located in two lineages. The selection pressures on CVB2 strains of D genotype and CVB5 strains of F geno-type circulating in China in recent years were 0. 037 and 0. 036, respectively. Six positively selected amino acid sites were found in the VP1 region of CVB5 strains, but no positively selected amino acid site was found in the VP1 region of CVB2 strains. Conclusion HEV-B species was an essential component of the etiologic spectrum of HFMD in Anyang area during 2011 to 2015, of which CVB5 and CVB2 were the predominant se-rotypes. The VP1 region of CVB5 was more complex and active than that of CVB2 over the course of evolution.

Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity.

Human HYPK (Huntingtin Yeast-two-hybrid Protein K) is an intrinsically unstructured chaperone-like protein with no sequence homology to known chaperones. HYPK is also known to be a part of ribosome-associated protein complex and present in polysomes. The objective of the present study was to investigate the evolutionary influence on HYPK primary structure and its impact on the protein’s function. Amino acid sequence analysis revealed 105 orthologs of human HYPK from plants, lower invertebrates to mammals. C-terminal part of HYPK was found to be particularly conserved and to contain nascent polypeptide-associated alpha subunit (NPAA) domain. This region experiences highest selection pressure, signifying its importance in the structural and functional evolution. NPAA domain of human HYPK has unique amino acid composition preferring glutamic acid and happens to be more stable from a conformational point of view having higher content of α-helices than the rest. Cell biology studies indicate that overexpressed C-terminal human HYPK can interact with nascent proteins, co-localizes with huntingtin, increases cell viability and decreases caspase activities in Huntington’s disease (HD) cell culture model. This domain is found to be required for the chaperone-like activity of HYPK in vivo. Our study suggested that by virtue of its flexibility and nascent peptide binding activity, HYPK may play an important role in assisting protein (re)folding.

Development of physiological resistance and its stage specificity in Culex quinquefasciatus after selection with deltamethrin in Assam, India

The study investigated the development and stage specificity of physiological resistance to insecticides in a colony of Culex quinquefasciatus Say (Diptera: Culicidae) mosquitoes, which are vectors of bancroftian filariasis in India, after selection with deltamethrin. Resistance was selected by exposing the larvae to the concentration of deltamethrin that caused 50 percent mortality in the tested population (i.e., LC50). Under continuous selection pressure, the LC50 increased steadily in subsequent generations. The estimated LC50 for the F0 generation was 0.409 μg/L; the LC50 first displayed a substantial increase in the F5 generation (5.616 μg/L) and reached 121.902 μg/L in the F10 generation. The objective of this study was to establish a deltamethrin-resistant colony to develop a research programme that will study the evolution of physiological resistance patterns and stage-specific resistance responses in Cx. quinquefasciatus larvae and adults under laboratory conditions. An approximately 298-fold increase in resistance was recorded after 10 generations, as evidenced by the resistance ratio (RR50). The progress and effect of the selection pressure in the adult stage was monitored with the World Health Organisation (WHO) diagnostic test. The mortality, as observed using the WHO diagnostic test, declined significantly from the F5 generation (85 percent) onwards and the highest rate of survival (65 percent) was observed in the F10 generation.

Positive Selection Analysis of VP1 Genes of Worldwide Human Enterovirus 71 Viruses / 中国病毒学·英文版

Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.

Selection Pressure on Haemagglutinin Genes of H9N2 Influenza Viruses from Different Hosts / 中国病毒学·英文版

Positive selection and differential selective pressure analyses were carried out to study Haemagglutinin (HA) genes of H9N2 influenza viruses from different hosts in this paper. Results showed that, although most positions in HAs were under neutral or purifying evolution, a few positions located in the antigenic regions and receptor binding sites were subject to positive selection and some of them were even positively selected at the population level. In addition, there were always some positions differentially selected for viruses from different hosts. Both selection pressure working on HA codons and positions differentially selected might account for the extension of the host range and adaptations to different hosts of H9N2 influenza viruses.