Genetic diversity in two leading Plasmodium vivax malaria vaccine candidates AMA1 and MSP119 at three sites in India

Plasmodium vivax, a major contributor to the malaria burden in India, has the broadest geographic distribution and shows higher genetic diversity than P. falciparum. Here, we investigated the genetic diversity of two leading P. vivax vaccine candidate antigens, at three geographically diverse malaria-endemic regions in India. Pvama1 and Pvmsp119 partial coding sequences were generated from one hundred P. vivax isolates in India (Chennai n = 28, Nadiad n = 50 and Rourkela n = 22) and ~1100 published sequences from Asia, South America, North America, and Oceania regions included. These data were used to assess the genetic diversity and potential for vaccine candidacy of both antigens on a global scale. A total of 44 single nucleotide polymorphism (SNPs) were identified among 100 Indian Pvama1 sequences, including 10 synonymous and 34 nonsynonymous mutations. Nucleotide diversity was higher in Rourkela and Nadiad as compared to Chennai. Nucleotide diversity measures showed a strong balancing selection in Indian and global population for domain I of Pvama1, which suggests that it is a dominant target of the protective immune response. In contrast, the Pvmsp119 region showed highly conserved sequences in India and across the Oceania, South America, North America and Asia, demonstrating low genetic diversity in the global population when compared to Pvama1. Results suggest the possibility of including Pvmsp119 in a multivalent vaccine formulation against P. vivax infections. However, the high genetic diversity seen in Pvama1 would be more challenging for vaccine development.

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Genetic Diversity of Plasmodium vivax Reticulocyte Binding Protein 2b in Global Parasite Populations

10.21203/rs.3.rs-1023914/v1 ◽

2021 ◽

Author(s):

xuexing zhang ◽

Haichao Wei ◽

Yangminghui Zhang ◽

Yan Zhao ◽

Lin Wang ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Vaccine Development ◽

Balancing Selection ◽

Binding Protein ◽

Critical Role ◽

Binding Region ◽

Geographical Separation ◽

Antibody Titers ◽

Parasite Populations

Abstract BackgroundPlasmodium vivax reticulocyte binding protein 2b (PvRBP2b) plays a critical role in parasite invasion of reticulocytes by binding the transferring receptor 1. PvRBP2b is a vaccine candidate since the antibody titers against PvRBP2b recombinant proteins are negatively correlated with the parasitemia and risk of vivax malaria. This study aims to analyze the genetic diversity of the PvRBP2b gene in the global P. vivax populations. MethodsThe near full-length PvRBP2b nucleotide sequences (190-8349 bp) were obtained from 88 P. vivax isolates collected from the China–Myanmar border (n=44) and Thailand (n=44). Additional 224 sequences of PvRBP2b were retrieved from genome sequences from the global parasite populations. The genetic diversity, neutral selections, haplotypes distribution and genetic differentiation of PvRBP2b were examined. ResultsThe genetic diversity of PvRBP2b was distributed unevenly with the peak in the reticulocyte binding region in the N-terminus and subjected to the balancing selection. Several amino acid variants were found in all or nearly all endemic fields. However, the critical residues responsible for reticulocyte binding were highly conserved. There was substantial population differentiation according to the geographical separation. The distribution of haplotypes in the reticulocyte binding region varied among regions; even the two major haplotypes Hap_6 and Hap_8 were found in only five populations. ConclusionsOur data showed considerable genetic variations of PvRBPb in global parasite populations, and the geographic divergence may pose a challenge to PvRBP2b-based vaccine development.

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Contrasting epidemiology and population genetics of COVID-19 infections defined with 74 polymorphic loci in SARS-CoV-2 genomes sampled globally.

10.1101/2021.04.25.21255897 ◽

2021 ◽

Author(s):

Felicia Chan ◽

Ricardo Ataide ◽

Jack S Richards ◽

Charles Akugbey Narh

Keyword(s):

Genetic Diversity ◽

Population Genetics ◽

North America ◽

South America ◽

Age Groups ◽

Geographic Region ◽

Polymorphic Loci ◽

Geographical Regions ◽

Global Population ◽

Close Relatedness

SARS-CoV-2, the coronavirus causing COVID-19, has infected and killed several millions of people worldwide. Since the first COVID-19 outbreak in December 2019, SARS-CoV-2 has evolved with a few genetic variants associated with higher infectivity. We aimed to identify polymorphic loci in SARS-CoV-2 that can be used to define and monitor the viral epidemiology and population genetics in different geographical regions. Between December 2019 and September 2020, we sampled 5,959 SARS-CoV-2 genomes. More than 80% of the genomes sampled in Africa, Asia, Europe, North America, Oceania and South America were reportedly isolated from clinical infections in older patients, ≥ 20 years. We used the first indexed genome (NC_045512.2) as a reference and constructed multilocus genotypes (MLGs) for each sampled genome based on amino acids detected at 74 polymorphic loci located in ORF1ab, ORF3a, ORF8, matrix (M), nucleocapsid (N) and spike (S) genes. Eight of the 74 loci were informative in estimating the risk of carrying infections with mutant alleles among different age groups, gender and geographical regions. Four mutant alleles - ORF1ab L4715, S G614, and N K203 and R204 reached 90% prevalence globally, coinciding with peaks in transmission but not COVID-19 severity, from March to August 2020. During this period, the MLG genetic diversity was moderate in Asia, Oceania and North America; in contrast to Africa, Europe and South America, where lower genetic diversity and absence of linkage disequilibrium indicated clonal SARS-CoV-2 transmission. Despite close relatedness to Asian MLGs, MLGs in the global population were genetically differentiated by geographic region, suggesting structure in SARS-CoV-2 populations. Our findings demonstrate the utility of the 74 loci as a genetic tool to study and monitor SARS-CoV-2 transmission dynamics and evolution, which can inform future control interventions.

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

Genes ◽

10.3390/genes12010029 ◽

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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High genetic diversity but low population structure in the frog Pseudopaludicola falcipes (Hensel, 1867) (Amphibia, Anura) from the Pampas of South America

Molecular Phylogenetics and Evolution ◽

10.1016/j.ympev.2015.11.012 ◽

2016 ◽

Vol 95 ◽

pp. 137-151 ◽

Cited By ~ 12

Author(s):

José A. Langone ◽

Arley Camargo ◽

Rafael O. de Sá

Keyword(s):

Genetic Diversity ◽

Population Structure ◽

South America ◽

High Genetic Diversity

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Molecular Typing Reveals High Genetic Diversity of Xanthomonas translucens Strains Infecting Small-Grain Cereals in Iran

Applied and Environmental Microbiology ◽

10.1128/aem.01518-19 ◽

2019 ◽

Vol 85 (20) ◽

Cited By ~ 2

Author(s):

Moein Khojasteh ◽

S. Mohsen Taghavi ◽

Pejman Khodaygan ◽

Habiballah Hamzehzarghani ◽

Gongyou Chen ◽

...

Keyword(s):

Genetic Diversity ◽

Population Structure ◽

Global Scale ◽

Population Diversity ◽

Bacterial Leaf Streak ◽

High Genetic Diversity ◽

Center Of Origin ◽

Content Type ◽

Xanthomonas Translucens ◽

Insight Into

ABSTRACT This study provides a phylogeographic insight into the population diversity of Xanthomonas translucens strains causing bacterial leaf streak disease of small-grain cereals in Iran. Among the 65 bacterial strains isolated from wheat, barley, and gramineous weeds in eight Iranian provinces, multilocus sequence analysis and typing (MLSA and MLST) of four housekeeping genes (dnaK, fyuA, gyrB, and rpoD), identified 57 strains as X. translucens pv. undulosa, while eight strains were identified as X. translucens pv. translucens. Although the pathogenicity patterns on oat and ryegrass weed species varied among the strains, all X. translucens pv. undulosa strains were pathogenic on barley, Harding’s grass, rye (except for XtKm35) and wheat, and all X. translucens pv. translucens strains were pathogenic on barley and Harding’s grass, while none of the latter group was pathogenic on rye or wheat (except for XtKm18). MLST using the 65 strains isolated in Iran, as well as the sequences of the four genes from 112 strains of worldwide origin retrieved from the GenBank database, revealed higher genetic diversity (i.e., haplotype frequency, haplotype diversity, and percentage of polymorphic sites) among the Iranian population of X. translucens than among the North American strains of the pathogen. High genetic diversity of the BLS pathogen in Iran was in congruence with the fact that the Iranian Plateau is considered the center of origin of cultivated wheat. However, further studies using larger collections of strains are warranted to precisely elucidate the global population diversity and center of origin of the pathogen. IMPORTANCE Bacterial leaf streak (BLS) of small-grain cereals (i.e., wheat and barley) is one of the economically important diseases of gramineous crops worldwide. The disease occurs in many countries across the globe, with particular importance in regions characterized by high levels of precipitation. Two genetically distinct xanthomonads—namely, Xanthomonas translucens pv. undulosa and X. translucens pv. translucens—have been reported to cause BLS disease on small-grain cereals. As seed-borne pathogens, the causal agents are included in the A2 list of quarantine pathogens by the European and Mediterranean Plant Protection Organization (EPPO). Despite its global distribution and high economic importance, the population structure, genetic diversity, and phylogeography of X. translucens remain undetermined. This study, using MLSA and MLST, provides a global-scale phylogeography of X. translucens strains infecting small-grain cereals. Based on the diversity parameters, neutrality indices, and population structure, we observe higher genetic diversity of the BLS pathogen in Iran, which is geographically close to the center of origin of common wheat, than has so far been observed in other areas of the world, including North America. The results obtained in this study provide a novel insight into the genetic diversity and population structure of the BLS pathogen of small-grain cereals on a global scale.

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The Sri Lankan paradox: high genetic diversity in Plasmodium vivax populations despite decreasing levels of malaria transmission – ERRATUM

Parasitology ◽

10.1017/s0031182014000444 ◽

2014 ◽

Vol 141 (7) ◽

pp. 891-891

Keyword(s):

Genetic Diversity ◽

Plasmodium Vivax ◽

Malaria Transmission ◽

Sri Lankan ◽

High Genetic Diversity

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The Sri Lankan paradox: high genetic diversity in Plasmodium vivax populations despite decreasing levels of malaria transmission

Parasitology ◽

10.1017/s0031182013002278 ◽

2014 ◽

Vol 141 (7) ◽

pp. 880-890 ◽

Cited By ~ 39

Author(s):

SHARMINI GUNAWARDENA ◽

MARCELO U. FERREIRA ◽

G. M. G. KAPILANANDA ◽

DYANN F. WIRTH ◽

NADIRA D. KARUNAWEERA

Keyword(s):

Genetic Diversity ◽

Sri Lanka ◽

Plasmodium Vivax ◽

Malaria Transmission ◽

Population Size ◽

Effective Population Size ◽

Allele Frequency Distribution ◽

Effective Population ◽

High Genetic Diversity ◽

Mode Shift

SUMMARYHere we examined whether the recent dramatic decline in malaria transmission in Sri Lanka led to a major bottleneck in the local Plasmodium vivax population, with a substantial decrease in the effective population size. To this end, we typed 14 highly polymorphic microsatellite markers in 185 P. vivax patient isolates collected from 13 districts in Sri Lanka over a period of 5 years (2003–2007). Overall, we found a high degree of polymorphism, with 184 unique haplotypes (12–46 alleles per locus) and average genetic diversity (expected heterozygosity) of 0·8744. Almost 69% (n = 127) isolates had multiple-clone infections (MCI). Significant spatial and temporal differentiation (FST = 0·04–0·25; P⩽0·0009) between populations was observed. The effective population size was relatively high but showed a decline from 2003–4 to 2006–7 periods (estimated as 45 661 to 22 896 or 10 513 to 7057, depending on the underlying model used). We used three approaches – namely, mode-shift in allele frequency distribution, detection of heterozygote excess and the M-ratio statistics – to test for evidence of a recent population bottleneck but only the low values of M-ratio statistics (ranging between 0·15–0·33, mean 0·26) were suggestive of such a bottleneck. The persistence of high genetic diversity and high proportion of MCI, with little change in effective population size, despite the collapse in demographic population size of P. vivax in Sri Lanka indicates the importance of maintaining stringent control and surveillance measures to prevent resurgence.

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Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders

Parasites & Vectors ◽

10.1186/s13071-019-3803-2 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Yubing Hu ◽

Lin Wang ◽

Huguette Gaelle Ngassa Mbenda ◽

Myat Thu Soe ◽

Chunyun Yu ◽

...

Keyword(s):

Genetic Diversity ◽

Natural Selection ◽

Genetic Differentiation ◽

Plasmodium Vivax ◽

Binding Protein ◽

Duffy Binding Protein ◽

High Genetic Diversity ◽

Low Level ◽

Malaria Epidemiology ◽

Greater Mekong Subregion

Abstract Background Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology with Plasmodium vivax becoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity of P. vivax Duffy-binding protein gene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from global P. vivax populations. Methods pvdbp-II sequences were obtained from 85 and 82 clinical P. vivax isolates from the eastern and western Myanmar borders, respectively. In addition, 504 pvdbp-II sequences from nine P. vivax populations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population. Results The nucleotide diversity of the pvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected in pvdbp-II gene in P. vivax isolates from the eastern Myanmar area. P. vivax parasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000–0.099). Population genetic structure analysis of the pvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) in P. vivax populations from the eastern and western borders of Myanmar. Conclusions The pvdbp-II gene is genetically diverse in the eastern and western Myanmar border P. vivax populations. Positive natural selection and recombination occurred in pvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of the P. vivax populations in the GMS. These results can help understand the evolution of the P. vivax populations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.

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Polymorphism in the major histocompatibility complex (MHC class II B) genes of the Rufous-backed Bunting (Emberiza jankowskii)

PeerJ ◽

10.7717/peerj.2917 ◽

2017 ◽

Vol 5 ◽

pp. e2917 ◽

Cited By ~ 2

Author(s):

Dan Li ◽

Keping Sun ◽

Yunjiao Zhao ◽

Aiqing Lin ◽

Shi Li ◽

...

Keyword(s):

Genetic Diversity ◽

Major Histocompatibility Complex ◽

Mhc Class Ii ◽

Nucleotide Diversity ◽

Environmental Changes ◽

Major Histocompatibility ◽

High Genetic Diversity ◽

Exon 2 ◽

Histocompatibility Complex ◽

Segregating Sites

Genetic diversity is one of the pillars of conservation biology research. High genetic diversity and abundant genetic variation in an organism may be suggestive of capacity to adapt to various environmental changes. The major histocompatibility complex (MHC) is known to be highly polymorphic and plays an important role in immune function. It is also considered an ideal model system to investigate genetic diversity in wildlife populations. The Rufous-backed Bunting (Emberiza jankowskii) is an endangered species that has experienced a sharp decline in both population and habitat size. Many historically significant populations are no longer present in previously populated regions, with only three breeding populations present in Inner Mongolia (i.e., the Aolunhua, Gahaitu and Lubei557 populations). Efforts focused on facilitating the conservation of the Rufous-backed Bunting (Emberiza jankowskii) are becoming increasingly important. However, the genetic diversity ofE. jankowskiihas not been investigated. In the present study, polymorphism in exon 2 of the MHCIIB ofE. jankowskiiwas investigated. This polymorphism was subsequently compared with a related species, the Meadow Bunting (Emberiza cioides). A total of 1.59 alleles/individual were detected inE. jankowskiiand 1.73 alleles/individual were identified inE.cioides. The maximum number of alleles per individual from the threeE. jankowskiipopulations suggest the existence of at least three functional loci, while the maximum number of alleles per individual from the threeE. cioidespopulations suggest the presence of at least four functional loci. Two of the alleles were shared between theE. jankowskiiandE. cioides. Among the 12 unique alleles identified inE. jankowskii, 10.17 segregating sites per allele were detected, and the nucleotide diversity was 0.1865. Among the 17 unique alleles identified inE. cioides, eight segregating sites per allele were detected, and the nucleotide diversity was 0.1667. Overall, compared to other passerine birds, a relatively low level of MHC polymorphism was revealed inE. jankowskii, which was similar to that inE. cioides. Positive selection was detected by PAML/SLAC/FEL analyses in the region encoding the peptide-binding region in both species, and no recombination was detected. Phylogenetic analysis showed that the alleles fromE. jankowskiiandE. cioidesbelong to the same clade and the two species shared similar alleles, suggesting the occurrence of a trans-species polymorphism between the twoEmberizaspecies.

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