Mosaic aneuploidy in Leishmania: the perspective of whole genome sequencing

Dujardin, Jean‐Claude; Mannaert, An; Durrant, Caroline; Cotton, James A.

doi:10.1016/j.pt.2014.09.004

Cited by 20 publications

(19 citation statements)

References 12 publications

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“…Here, relative somy between chromosomes is inferred from the coverage depth of reads mapped to each chromosome, while the baseline somy is determined from the allele frequency distribution. In principle, this could be misleading if the samples sequenced were mixtures of clones with many different somy levels, and single cell approaches such as FISH or single cell sequencing would be needed to fully disentangle this [53]. However, the differences in allele frequency distributions between DM62 and DM299 for many chromosomes is particularly striking (Fig 2B), so there are at least genuine differences in the complement of chromosomes between the sequenced isolates.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Genomic analysis of natural intra-specific hybrids among Ethiopian isolates of Leishmania donovani

et al. 2020

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Parasites of the genus Leishmania (Kinetoplastida: Trypanosomatidae) cause widespread and devastating human diseases. Visceral leishmaniasis due to Leishmania donovani is endemic in Ethiopia where it has also been responsible for major epidemics. The presence of hybrid genotypes has been widely reported in surveys of natural populations, genetic variation reported in a number of Leishmania species, and the extant capacity for genetic exchange demonstrated in laboratory experiments. However, patterns of recombination and the evolutionary history of admixture that produced these hybrid populations remain unclear. Here, we use whole-genome sequence data to investigate Ethiopian L. donovani isolates previously characterized as hybrids by microsatellite and multi-locus sequencing. To date there is only one previous study on a natural population of Leishmania hybrids based on whole-genome sequences. We propose that these hybrids originate from recombination between two different lineages of Ethiopian L. donovani occurring in the same region. Patterns of inheritance are more complex than previously reported with multiple, apparently independent, origins from similar parents that include backcrossing with parental types. Analysis indicates that hybrids are representative of at least three different histories. Furthermore, isolates were highly polysomic at the level of chromosomes with differences between parasites recovered from a recrudescent infection from a previously treated individual. The results demonstrate that recombination is a significant feature of natural populations and contributes to the growing body of data that shows how recombination, and gene flow, shape natural populations of Leishmania.

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Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Genomic analysis of natural intra-specific hybrids among Ethiopian isolates of Leishmania donovani

et al. 2020

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“…However, the underlying genetic mechanisms that drive short-term Leishmania evolution are still largely unknown. In the absence of classical transcriptional gene regulation, these early-branching eukaryotes often control protein abundance via gene and chromosome amplification 10,16 .…”

Section: Introductionmentioning

confidence: 99%

Haplotype selection as an adaptive mechanism in the protozoan pathogen Leishmania donovani

et al. 2017

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The parasite Leishmania donovani causes a fatal disease termed visceral leishmaniasis. The process through which the parasite adapts to environmental change remains largely unknown. Here we show that aneuploidy is integral for parasite adaptation and that karyotypic fluctuations allow for selection of beneficial haplotypes, which impact transcriptomic output and correlate with phenotypic variations in proliferation and infectivity. To avoid loss of diversity following karyotype and haplotype selection, L. donovani utilizes two mechanisms: polyclonal selection of beneficial haplotypes to create coexisting subpopulations that preserve the original diversity, and generation of new diversity as aneuploidy-prone chromosomes tolerate higher mutation rates. Our results reveal high aneuploidy turnover and haplotype selection as a unique evolutionary adaptation mechanism that L. donovani uses to preserve genetic diversity under strong selection. This unexplored process may function in other human diseases, including fungal infection and cancer, and stimulate innovative treatment options.

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“…multiple chromosome are found that deviate from the expected diploid configuration(66, 67); most frequently, the chromosomes are >diploid(3-5 N) but also occasionally haploid(68,69), and fluorescent in situ hybridisation suggests that individual chromosome ploidy changes with growth(70). Very recently, similar genome-wide aneuploidy has been described in T. cruzi(71), indicating it is not limited to Leishmania.…”

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confidence: 87%

The protozoan nucleus

McCulloch

Navarro

2016

Molecular and Biochemical Parasitology

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The nucleus is arguably the defining characteristic of eukaryotes, distinguishing their cell organisation from both bacteria and archaea. Though the evolutionary history of the nucleus remains the subject of debate, its emergence differs from several other eukaryotic organelles in that it appears not to have evolved through symbiosis, but by cell membrane elaboration from an archaeal ancestor. Evolution of the nucleus has been accompanied by elaboration of nuclear structures that are intimately linked with most aspects of nuclear genome function, including chromosome organisation, DNA maintenance, replication and segregation, and gene expression controls. Here we discuss the complexity of the nucleus and its substructures in protozoan eukaryotes, with a particular emphasis on divergent aspects in eukaryotic parasites, which shed light on nuclear function throughout eukaryotes and reveal specialisations that underpin pathogen biology.

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Mosaic aneuploidy in Leishmania: the perspective of whole genome sequencing

Cited by 20 publications

References 12 publications

Genomic analysis of natural intra-specific hybrids among Ethiopian isolates of Leishmania donovani

Genomic analysis of natural intra-specific hybrids among Ethiopian isolates of Leishmania donovani

Haplotype selection as an adaptive mechanism in the protozoan pathogen Leishmania donovani

The protozoan nucleus

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