Whole genome sequencing of field isolates reveals extensive genetic diversity in Plasmodium vivax from Colombia

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations is affects. Its control and eventual elimination are a global health priority. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission. Here we analyze whole genome data from eight field samples from a region in Cord ́ oba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this parasite. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 microsatellite loci that are polymorphic and easy to score and can thus be used in epidemiological investigations in South America.

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Population-level genome-wide STR typing in Plasmodium species reveals higher resolution population structure and genetic diversity relative to SNP typing

10.1101/2021.05.19.444768 ◽

2021 ◽

Author(s):

Jiru Han ◽

Jacob E Munro ◽

Anthony Kocoski ◽

Alyssa E Barry ◽

Melanie Bahlo

Keyword(s):

Genetic Diversity ◽

Large Scale ◽

Tandem Repeats ◽

Plasmodium Species ◽

Whole Genome Sequence ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Genome Wide ◽

Field Samples

Short tandem repeats (STRs) are highly informative genetic markers that have been used extensively in population genetics analysis. They are an important source of genetic diversity and can also have functional impact. Despite the availability of bioinformatic methods that permit large-scale genome-wide genotyping of STRs from whole genome sequencing data, they have not previously been applied to sequencing data from large collections of malaria parasite field samples. Here, we have genotyped STRs using HipSTR in more than 3,000 Plasmodium falciparum and 174 Plasmodium vivax published whole-genome sequence data from samples collected across the globe. High levels of noise and variability in the resultant callset necessitated the development of a novel method for quality control of STR genotype calls. A set of high-quality STR loci (6,768 from P. falciparum and 3,496 from P. vivax) were used to study Plasmodium genetic diversity, population structures and genomic signatures of selection and these were compared to genome-wide single nucleotide polymorphism (SNP) genotyping data. In addition, the genome-wide information about genetic variation and other characteristics of STRs in P. falciparum and P. vivax have been made available in an interactive web-based R Shiny application PlasmoSTR (https://github.com/bahlolab/PlasmoSTR).

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Population-level genome-wide STR discovery and validation for population structure and genetic diversity assessment of Plasmodium species

PLoS Genetics ◽

10.1371/journal.pgen.1009604 ◽

2022 ◽

Vol 18 (1) ◽

pp. e1009604

Author(s):

Jiru Han ◽

Jacob E. Munro ◽

Anthony Kocoski ◽

Alyssa E. Barry ◽

Melanie Bahlo

Keyword(s):

Genetic Diversity ◽

Tandem Repeats ◽

Plasmodium Species ◽

Whole Genome Sequence ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Genome Wide ◽

Diversity Assessment ◽

Field Samples

Short tandem repeats (STRs) are highly informative genetic markers that have been used extensively in population genetics analysis. They are an important source of genetic diversity and can also have functional impact. Despite the availability of bioinformatic methods that permit large-scale genome-wide genotyping of STRs from whole genome sequencing data, they have not previously been applied to sequencing data from large collections of malaria parasite field samples. Here, we have genotyped STRs using HipSTR in more than 3,000 Plasmodium falciparum and 174 Plasmodium vivax published whole-genome sequence data from samples collected across the globe. High levels of noise and variability in the resultant callset necessitated the development of a novel method for quality control of STR genotype calls. A set of high-quality STR loci (6,768 from P. falciparum and 3,496 from P. vivax) were used to study Plasmodium genetic diversity, population structures and genomic signatures of selection and these were compared to genome-wide single nucleotide polymorphism (SNP) genotyping data. In addition, the genome-wide information about genetic variation and other characteristics of STRs in P. falciparum and P. vivax have been available in an interactive web-based R Shiny application PlasmoSTR (https://github.com/bahlolab/PlasmoSTR).

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Whole-genome sequencing reveals the extent of heterozygosity in a preferentially self-fertilizing hermaphroditic vertebrate

Genome ◽

10.1139/gen-2017-0188 ◽

2018 ◽

Vol 61 (4) ◽

pp. 241-247 ◽

Cited By ~ 8

Author(s):

Luana S.F. Lins ◽

Shawn Trojahn ◽

Alexandra Sockell ◽

Muh-Ching Yee ◽

Andrey Tatarenkov ◽

...

Keyword(s):

Genetic Diversity ◽

Genome Sequencing ◽

Phylogenetic Relationships ◽

Whole Genome ◽

Mangrove Forests ◽

Nucleotide Polymorphisms ◽

Sequencing Data ◽

Full Genome Sequencing ◽

Genome Data ◽

Mangrove Rivulus

The mangrove rivulus, Kryptolebias marmoratus, is one of only two self-fertilizing hermaphroditic fish species and inhabits mangrove forests. While selfing can be advantageous, it reduces heterozygosity and decreases genetic diversity. Studies using microsatellites found that there are variable levels of selfing among populations of K. marmoratus, but overall, there is a low rate of outcrossing and, therefore, low heterozygosity. In this study, we used whole-genome data to assess the levels of heterozygosity in different lineages of the mangrove rivulus and infer the phylogenetic relationships among those lineages. We sequenced whole genomes from 15 lineages that were completely homozygous at microsatellite loci and used single nucleotide polymorphisms (SNPs) to determine heterozygosity levels. More variation was uncovered than in studies using microsatellite data because of the resolution of full genome sequencing data. Moreover, missense polymorphisms were found most often in genes associated with immune function and reproduction. Inferred phylogenetic relationships suggest that lineages largely group by their geographic distribution. The use of whole-genome data provided further insight into genetic diversity in this unique species. Although this study was limited by the number of lineages that were available, these data suggest that there is previously undescribed variation within lineages of K. marmoratus that could have functional consequences and (or) inform us about the limits to selfing (e.g., genetic load, accumulation of deleterious mutations) and selection that might favor the maintenance of heterozygosity. These results highlight the need to sequence additional individuals within and among lineages.

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Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America

Malaria Journal ◽

10.1186/1475-2875-13-392 ◽

2014 ◽

Vol 13 (1) ◽

pp. 392 ◽

Cited By ~ 9

Author(s):

Mette L Schousboe ◽

Samir Ranjitkar ◽

Rupika S Rajakaruna ◽

Priyanie H Amerasinghe ◽

Flemming Konradsen ◽

...

Keyword(s):

Genetic Diversity ◽

South America ◽

Plasmodium Vivax ◽

Microsatellite Loci ◽

Global And Local

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Genomic Uniqueness of Local Sheep Breeds From Morocco

Frontiers in Genetics ◽

10.3389/fgene.2021.723599 ◽

2021 ◽

Vol 12 ◽

Author(s):

Abdessamad Ouhrouch ◽

Simon Boitard ◽

Frédéric Boyer ◽

Bertrand Servin ◽

Anne Da Silva ◽

...

Keyword(s):

Genetic Diversity ◽

Demographic History ◽

Large Set ◽

Whole Genome ◽

Selection Signatures ◽

Effective Population ◽

High Genetic Diversity ◽

Sheep Breeds ◽

Genome Data ◽

Genomic Regions

Sheep farming is a major source of meat in Morocco and plays a key role in the country’s agriculture. This study aims at characterizing the whole-genome diversity and demographic history of the main Moroccan sheep breeds, as well as to identify selection signatures within and between breeds. Whole genome data from 87 individuals representing the five predominant local breeds were used to estimate their level of neutral genetic diversity and to infer the variation of their effective population size over time. In addition, we used two methods to detect selection signatures: either for detecting selective sweeps within each breed separately or by detecting differentially selected regions by contrasting different breeds. We identified hundreds of genomic regions putatively under selection, which related to several biological terms involved in local adaptation or the expression of zootechnical performances such as Growth, UV protection, Cell maturation or Feeding behavior. The results of this study revealed selection signatures in genes that have an important role in traits of interest and increased our understanding of how genetic diversity is distributed in these local breeds. Thus, Moroccan local sheep breeds exhibit both a high genetic diversity and a large set of adaptive variations, and therefore, represent a valuable genetic resource for the conservation of sheep in the context of climate change.

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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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