Genetic diversity in the IZUMO1-JUNO protein-receptor pair involved in human reproduction

Fertilization in mammals begins with the union of egg and sperm, an event that starts a cascade of cellular processes. The molecular-level understanding of these processes can guide the development of new strategies for controlling and/or promoting fertilization, and inform researchers and medical professional on the best choice of interventions. The proteins encoded by the IZUMO1 and JUNO genes form a ligand-receptor protein pair involved in the recognition of sperm and egg. Due to their role in the fertilization process, these proteins are potential targets for the development of novel anti-contraceptive, as well as infertility treatments. Here we present a comprehensive analysis of these gene sequences, with the objective of identifying evolutionary patterns that may support their relevance as targets for preventing or improving fertility among humans. JUNO and IZUMO1 gene sequences were identified within the genomes of over 2,000 humans sequenced in the 1000 Genomes Project. The human sequences were subjected to analyses of nucleotide diversity, deviation from neutrality of genetic variation, population-based differentiation (FST), haplotype inference, and whole chromosome scanning for signals of positive or of balancing selection. Derived alleles were determined by comparison to archaic hominin and other primate genomes. The potential effect of common non-synonymous variants on protein-protein interaction was also assessed. IZUMO1 displays higher variability among human individuals than JUNO. Genetic differentiation between continental population pairs was within whole-genome estimates for all but the JUNO gene in the African population group with respect to the other 4 population groups (American, East Asian, South Asian, and European). Tajima’s D values demonstrated deviation from neutrality for both genes in comparison to a group of genes identified in the literature as under balancing or positive selection. Tajima’s D for IZUMO1 aligns with values calculated for genes presumed to be under balancing selection, whereas JUNO’s value aligned with genes presumed to be under positive selection. These inferences on selection are both supported by SNP density, nucleotide diversity and haplotype analysis. A JUNO haplotype carrying 3 derived alleles out of 5, one of which is a missense mutation implicated in polyspermy, was found to be significant in a population of African ancestry. Polyspermy has a disadvantageous impact on fertility and its presence in approximately 30% of the population of African ancestry may be associated to a potentially beneficial role of this haplotype. This role has not been established and may be related to a non-reproductive role of JUNO. The high degree of conservation of the JUNO sequence combined with a dominant haplotype across multiple population groups supports JUNO as a potential target for the development of contraceptive treatments. In addition to providing a detailed account of human genetic diversity across these 2 important and related genes, this study also provides a framework for large population-based studies investigating protein-protein interactions at the genome level.

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Genetic Diversity in the IZUMO1-JUNO Protein-Receptor Pair Involved in Human Reproduction

10.1101/2021.08.08.455586 ◽

2021 ◽

Author(s):

Wely B Floriano ◽

Jessica Allingham

Keyword(s):

Genetic Diversity ◽

Positive Selection ◽

Nucleotide Diversity ◽

Balancing Selection ◽

African Ancestry ◽

Population Based ◽

Gene Sequences ◽

Population Groups ◽

Tajima’S D

Fertilization in mammals begins with the union of egg and sperm, an event that starts a cascade of cellular processes. The molecular-level understanding of these processes can guide the development of new strategies for controlling and/or promoting fertilization, and inform researchers and medical professional on the best choice of interventions. The proteins encoded by the IZUMO1 and JUNO genes form a ligand-receptor protein pair involved in the recognition of sperm and egg. Due to their role in the fertilization process, these proteins are potential targets for the development of novel anti-contraceptive, as well as infertility treatments. Here we present a comprehensive analysis of these gene sequences, with the objective of identifying evolutionary patterns that may support their relevance as targets for preventing or improving fertility among humans. JUNO and IZUMO1 gene sequences were identified within the genomes of over 2000 humans sequenced in the 1000 Genomes Project. The human sequences were subjected to analyses of nucleotide diversity, selection neutrality, population-based differentiation (FST), haplotype inference, and whole chromosome scanning for signals of positive or of balancing selection. Derived alleles were determined by comparison to archaic hominin and other primate genomes. The potential effect of common non-synonymous variants on protein-protein interaction was also assessed. IZUMO1 displays higher variability among human individuals than JUNO. Genetic differentiation between continental population pairs was within whole-genome estimates for all but the JUNO gene in the African population group with respect to the other 4 population groups (American, East Asian, South Asian, and European). Tajima's D values demonstrated deviation from neutrality for both genes in comparison to a group of genes identified in the literature as under balancing or positive selection. Tajima's D for IZUMO1 aligns with values calculated for genes presumed to be under balancing selection, whereas JUNO's value aligned with genes presumed to be under positive selection. These inferences on selection are both supported by SNP density, nucleotide diversity and haplotype analysis. A JUNO haplotype carrying 3 derived alleles out of 5, one of which is a missense mutation implicated in polyspermy, was found to be significant in a population of African ancestry. Polyspermy has a disadvantageous impact on fertility and its presence in approximately 30% of the population of African ancestry may be associated to a potentially beneficial role of this haplotype. This role has not been established and may be related to a non-reproductive role of JUNO. The high degree of conservation of the JUNO sequence combined with a dominant haplotype across multiple population groups supports JUNO as a potential target for the development of contraceptive treatments. In addition to providing a detailed account of human genetic diversity across these 2 important and related genes, this study also provides a framework for large population-based studies investigating protein-protein interactions at the genome level.

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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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Population genetic analysis of the Plasmodium falciparum circumsporozoite protein in two distinct ecological regions in Ghana

Malaria Journal ◽

10.1186/s12936-020-03510-3 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Elikplim A. Amegashie ◽

Lucas Amenga-Etego ◽

Courage Adobor ◽

Peter Ogoti ◽

Kevin Mbogo ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Sequence Data ◽

Balancing Selection ◽

Population Expansion ◽

Circumsporozoite Protein ◽

Cape Coast ◽

Population Genetic Analysis ◽

Coastal Belt ◽

Tajima’S D

Abstract Background Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6–59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. Results Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. Conclusion The low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.

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Short Communication: Genetic diversity and phylogenetic analysis of two Indonesian local cattle breeds based on cytochrome b gene sequences

Biodiversitas Journal of Biological Diversity ◽

10.13057/biodiv/d200103 ◽

2018 ◽

Vol 20 (1) ◽

pp. 17-22

Author(s):

TETY HARTATIK ◽

DWI NUR HAPPY HARIYONO ◽

YUDI ADINATA

Keyword(s):

Genetic Diversity ◽

Phylogenetic Analysis ◽

Cytochrome B ◽

Nucleotide Diversity ◽

Haplotype Diversity ◽

Cytochrome B Gene ◽

Cyt B ◽

Gene Sequences ◽

Cattle Breeds ◽

Cyt B Gene

Hartatik T, Hariyono DNH, Adinata Y. 2019. Genetic diversity and phylogenetic analysis of two Indonesian local cattle breeds based on cytochrome b gene sequences. Biodiversitas 20: 17-22. Genetic diversity and phylogenetic relationships of two Indonesian local cattle breeds (Pasundan and Pacitan cattle) were investigated using mitochondrial DNA (mtDNA) cytochrome b (cyt b) gene analysis. Partial sequences of cyt b gene, 404 bp in length, were determined for 21 individuals from the two breeds. Genetic diversity of the breeds was assessed based on the number of polymorphic sites, number of haplotypes, haplotype diversity, nucleotide diversity and average number of differences. In addition, a neighbour-joining (NJ) haplotype tree was constructed based on Kimura’s two-parameter model. Among the two breeds, haplotype and nucleotide diversity of Pacitan cattle were the highest with values of 0.3778 and 0.00099, respectively. In contrast, Pasundan cattle had the lowest value for haplotype (0.1818) and nucleotide (0.00045) diversity. Four haplotypes (Hap_16, Hap_17, Hap_18 and Hap_19) were found across the two breeds and around 85.71% of investigated individuals were classified as Hap_16. Phylogenetic analysis with the inclusion of the cyt b sequences from 39 cattle breeds from Genbank database, showed that Indonesian cattle made a separated lineage together with Bos javanicus, B. bison, and B. bonasus. Pasundan and Pacitan cattle were considered from the same lineage based on haplotype distribution as well as phylogenetic analysis. This study may help the future researchers and livestock breeders for designing a breeding program based on a better understanding of the genetic diversity and history of local breeds.

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Population Genetic Analysis of Plasmodium falciparum Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana

10.21203/rs.3.rs-52164/v3 ◽

2020 ◽

Author(s):

Elikplim A Amegashie ◽

Lucas Amenga-Etego ◽

Courage Adobor ◽

Peter Ogoti ◽

Kevin Mbogo ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Sequence Data ◽

Balancing Selection ◽

Population Expansion ◽

Circumsporozoite Protein ◽

Cape Coast ◽

Population Genetic Analysis ◽

Coastal Belt ◽

Tajima’S D

Abstract Background Extensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. The transmission intensity and rates of recombination within and between populations influence the extent of its genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria-endemic areas such as Ghana. Methods Pfcsp sequences were retrieved from the Illumina-generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6-59 months presenting with clinical malaria at health facilities in Cape Coast (in the coastal belt) and Navrongo (Guinea savannah region), respectively, in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analysed for the allele frequency spectrum, genetic diversity both within the host and between populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. Results Pfcsp showed extensive diversity at the two sites, with the higher transmission site, Navrongo, exhibiting higher within-host and population-level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences, respectively. Between 1 and 6 amino acid variations were observed in the TH2R and TH3R epitope regions of PfCSP. Tajima’s D was negatively skewed, especially for the population from Cape Coast, given the expected historical population expansion. In contrast, a positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. Conclusion The low frequencies of the Pfcsp vaccine haplotype in the analysed populations indicate a need for additional molecular and immuno-epidemiological studies with broader temporal and geographic sampling in endemic populations targeted for RTS,S application. These results have implications for the efficacy of the vaccine in Ghana and will inform the choice of alleles to be included in future multivalent or chimeric vaccines.

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Study on Genetic Diversity of Phellodendron amurense based on cpDNA

E3S Web of Conferences ◽

10.1051/e3sconf/202127103059 ◽

2021 ◽

Vol 271 ◽

pp. 03059

Author(s):

Hongsheng Yang ◽

Donghong Yang ◽

Xuewen Yang ◽

Qingbo Zhou ◽

Haitao Cheng ◽

...

Keyword(s):

Genetic Diversity ◽

Northeast China ◽

Mismatch Distribution ◽

Nucleotide Diversity ◽

North China ◽

Haplotype Diversity ◽

Common Origin ◽

Ancestral Haplotype ◽

Phellodendron Amurense ◽

Tajima’S D

In this study, 3 haplotypes were found in populations of Phellodendron amurense based on two combined cpDNA regions (psbA-trnH and trnT-trnL). Nucleotide diversity and haplotype diversity were 0.43×10-3 and 0.41, respectively at the level of species. The AMOVA revealed that only 8.53% of the variation was explained by differences among geographical groups, whereas inter-population and intrapopulation differences explained 18.32% and 71.35% of the variation, respectively. Phylogeographical relationships showed that all haplotypes were clustered into two lineages. Haplotype H1 and H2 cluster together, and Haplotype H3 composed a group. TCS network of haplotypes showed that haplotype H1 located in the center of the lineage, and it appears to be an ancestral haplotype. So we hypothesized that Northeast China populations and North China populations had a common origin. The mismatch distribution of this species suggested that all populations and populations in North China had not undergone recent expansion, but populations in Northeast China had undergone recent expansion. The results were consistent with the results of Tajima’s D and Fu’s and Li’s D test.

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Population structure in the MHC region

10.1101/2021.10.25.465726 ◽

2021 ◽

Author(s):

Andre S Marostica ◽

Kelly Nunes ◽

Erick C Castelli ◽

Nayara SB Silva ◽

Bruce Weir ◽

...

Keyword(s):

Genetic Diversity ◽

Bone Marrow ◽

Population Structure ◽

Balancing Selection ◽

African Ancestry ◽

Human Diversity ◽

Hla Alleles ◽

Hla Genes ◽

Geographic Regions ◽

Genomic Regions

In his 1972 "The apportionment of human diversity", Richard Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection on specific genes and genomic regions can alter the apportionment of diversity. We examine genetic diversity at the HLA loci, located within the MHC region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The SNPs within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, with low FST values. However, when we analyze haplotypes defined by these SNPs (i.e., which define "HLA alleles"), we find marked differences in frequencies between geographic regions. These differences are not reflected in the FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We explore the case of Brazil's bone-marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry.

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Genome-wide scans for signatures of selection in Mangalarga Marchador horses using high-throughput SNP genotyping

BMC Genomics ◽

10.1186/s12864-021-08053-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wellington B. Santos ◽

Gustavo P. Schettini ◽

Amanda M. Maiorano ◽

Fernando O. Bussiman ◽

Júlio C. C. Balieiro ◽

...

Keyword(s):

Positive Selection ◽

Candidate Genes ◽

Limb Development ◽

Balancing Selection ◽

Phenotypic Traits ◽

Nadh Regeneration ◽

Recent Positive Selection ◽

Signatures Of Selection ◽

Genomic Regions ◽

Tajima’S D

Abstract Background The detection of signatures of selection in genomic regions provides insights into the evolutionary process, enabling discoveries regarding complex phenotypic traits. In this research, we focused on identifying genomic regions affected by different selection pressures, mainly highlighting the recent positive selection, as well as understanding the candidate genes and functional pathways associated with the signatures of selection in the Mangalarga Marchador genome. Besides, we seek to direct the discussion about genes and traits of importance in this breed, especially traits related to the type and quality of gait, temperament, conformation, and locomotor system. Results Three different methods were used to search for signals of selection: Tajima’s D (TD), the integrated haplotype score (iHS), and runs of homozygosity (ROH). The samples were composed of males (n = 62) and females (n = 130) that were initially chosen considering well-defined phenotypes for gait: picada (n = 86) and batida (n = 106). All horses were genotyped using a 670 k Axiom® Equine Genotyping Array (Axiom MNEC670). In total, 27, 104 (chosen), and 38 candidate genes were observed within the signatures of selection identified in TD, iHS, and ROH analyses, respectively. The genes are acting in essential biological processes. The enrichment analysis highlighted the following functions: anterior/posterior pattern for the set of genes (GLI3, HOXC9, HOXC6, HOXC5, HOXC4, HOXC13, HOXC11, and HOXC10); limb morphogenesis, skeletal system, proximal/distal pattern formation, JUN kinase activity (CCL19 and MAP3K6); and muscle stretch response (MAPK14). Other candidate genes were associated with energy metabolism, bronchodilator response, NADH regeneration, reproduction, keratinization, and the immunological system. Conclusions Our findings revealed evidence of signatures of selection in the MM breed that encompass genes acting on athletic performance, limb development, and energy to muscle activity, with the particular involvement of the HOX family genes. The genome of MM is marked by recent positive selection. However, Tajima’s D and iHS results point also to the presence of balancing selection in specific regions of the genome.

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Population Genetic Analysis of Plasmodium Falciparum Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana

10.21203/rs.3.rs-52164/v1 ◽

2020 ◽

Author(s):

Elikplim A Amegashie ◽

Lucas Amenga-Etego ◽

Courage Adobor ◽

Peter Ogoti ◽

Kevin Mbogo ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Sequence Data ◽

Balancing Selection ◽

Population Expansion ◽

Circumsporozoite Protein ◽

Cape Coast ◽

Population Genetic Analysis ◽

Coastal Belt ◽

Tajima’S D

Abstract BackgroundExtensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/ASO1 vaccine. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria endemic areas such as Ghana. MethodsPfcsp sequences were retrieved from Illumina generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6-59 months with clinical malaria presenting at health facilities in Cape Coast (on the coastal belt) and Navrongo (Guinea savannah region) respectively in Ghana. The sequences were mapped to the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analyzed for allele frequency spectrum, genetic diversity both within host and between the populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. ResultsPfcsp was extensively diverse at the two sites with higher transmission site, Navrongo, recording both higher within host and population level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences respectively. Amino acid variations ranging between 1 and 6 were observed in the TH2R and TH3R epitope regions of the PfCSP. Tajima’s D was negatively skewed especially for the population from Cape Coast given expected historical population expansion. On the contrary, positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. ConclusionThe low frequencies of Pfcsp vaccine haplotype in the populations analyzed calls for additional molecular and immuno-epidemiological studies with temporal and wider geographic sampling in endemic populations targeted for RTS,S application. These results have implications on the efficacy of the vaccine in Ghana and will inform the choice of alleles to include in future multivalent or chimeric vaccines.

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

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009652 ◽

2021 ◽

Vol 15 (8) ◽

pp. e0009652

Author(s):

Sonal Kale ◽

Veena Pande ◽

Om P. Singh ◽

Jane M. Carlton ◽

Prashant K. Mallick

Keyword(s):

Genetic Diversity ◽

North America ◽

South America ◽

Plasmodium Vivax ◽

Nucleotide Diversity ◽

Vaccine Development ◽

Balancing Selection ◽

Global Scale ◽

High Genetic Diversity ◽

Global Population

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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