Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania.
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.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, United Kingdom.
Matthew B
MB
Rogers
James D
JD
Hilley
Nicholas J
NJ
Dickens
Jon
J
Wilkes
Paul A
PA
Bates
Daniel P
DP
Depledge
David
D
Harris
Yerim
Y
Her
Pawel
P
Herzyk
Hideo
H
Imamura
Thomas D
TD
Otto
Mandy
M
Sanders
Kathy
K
Seeger
Jean-Claude
JC
Dujardin
Matthew
M
Berriman
Deborah F
DF
Smith
Christiane
C
Hertz-Fowler
Jeremy C
JC
Mottram
D001483:Base Sequence; D002875:Chromosomes / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D017125:Genes, Protozoan / Q000502:physiology*; D007891:Leishmania / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity