Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania

Abstract

Leishmania parasites cause a spectrum of clinical pathology in humans ranging from disfiguring cutaneous lesions to fatal visceral leishmaniasis. We have generated a reference genome for Leishmania mexicana and refined the reference genomes for Leishmania major, Leishmania infantum, and Leishmania braziliensis. This has allowed the identification of a remarkably low number of genes or paralog groups (2, 14, 19, and 67, respectively) unique to one species. These were found to be conserved in additional isolates of the same species. We have predicted allelic variation and find that in these isolates, L. major and L. infantum have a surprisingly low number of predicted heterozygous SNPs compared with L. braziliensis and L. mexicana. We used short read coverage to infer ploidy and gene copy numbers, identifying large copy number variations between species, with 200 tandem gene arrays in L. major and 132 in L. mexicana. Chromosome copy number also varied significantly between species, with nine supernumerary chromosomes in L. infantum, four in L. mexicana, two in L. braziliensis, and one in L. major. A significant bias against gene arrays on supernumerary chromosomes was shown to exist, indicating that duplication events occur more frequently on disomic chromosomes. Taken together, our data demonstrate that there is little variation in unique gene content across Leishmania species, but large-scale genetic heterogeneity can result through gene amplification on disomic chromosomes and variation in chromosome number. Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression in response to environmental conditions in the host, providing a genetic basis for disease tropism.

Adaptive mechanisms in pathogens: universal aneuploidy in Leishmania

“…The number of homologous chromosomes is also polymorphic. For example, although trisomy was observed at chromosome 1 in L. major strain Friedlin [23,25], this was not always found in other studies [17].…”

“…Although Leishmania is considered to be a diploid organism, supporting evidence is not abundant [22]. Several lines of evidence suggest that all Leishmania species are naturally aneuploid [16,17,26].…”

“…The chromosome copy numbers of two strains of L. major, L. mexicana, L. donovani, and one strain of L. braziliensis and L. infantum, were computed from genome-wide read depth coverage and showed the presence of supernumerary chromosomes in all samples: a mere twelve chromosomes were disomic in all samples [17]. L. braziliensis was predominantly triploid with some tetrasomies and one hexasomic chromosome, whereas the other strains and species had a more variable ploidy.…”

“…Recent advances in next-generation sequencing technologies boosted this research and provided a reference genome for other Leishmania species: a Nepalese Leishmania donovani [16], a Leishmania mexicana strain from Guatemala [17], as well as an African lizard-infecting sample, Leishmania tarentolae [18]. Data for Leishmania panamensis and Leishmania tropica and close relatives of Leishmania, Endotrypanum and Crithidia, are also available (www.ncbi.nlm.nih.gov/sra; www.tritrypdb.org).…”

Constitutive aneuploidy and genomic instability in the single‐celled eukaryote Giardia intestinalis

“…2011; Rogers et al. 2011). We applied a single‐cell‐oriented approach by evaluating the karyotypes of individual cells and individual nuclei within one cell.…”