Genome-wide stochastic adaptive DNA amplification at direct and inverted DNA repeats in the parasite Leishmania.
Gene amplification of specific loci has been described in all kingdoms of life. In the protozoan parasite Leishmania, the product of amplification is usually part of extrachromosomal circular or linear amplicons that are formed at the level of direct or inverted repeated sequences. A bioinformatics screen revealed that repeated sequences are widely distributed in the Leishmania genome and the repeats are chromosome-specific, conserved among species, and generally present in low copy number. Using sensitive PCR assays, we provide evidence that the Leishmania genome is continuously being rearranged at the level of these repeated sequences, which serve as a functional platform for constitutive and stochastic amplification (and deletion) of genomic segments in the population. This process is adaptive as the copy number of advantageous extrachromosomal circular or linear elements increases upon selective pressure and is reversible when selection is removed. We also provide mechanistic insights on the formation of circular and linear amplicons through RAD51 recombinase-dependent and -independent mechanisms, respectively. The whole genome of Leishmania is thus stochastically rearranged at the level of repeated sequences, and the selection of parasite subpopulations with changes in the copy number of specific loci is used as a strategy to respond to a changing environment.
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Jean-Michel
JM
Ubeda
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Frédéric
F
Raymond
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Angana
A
Mukherjee
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Marie
M
Plourde
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Hélène
H
Gingras
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Gaétan
G
Roy
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Andréanne
A
Lapointe
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Philippe
P
Leprohon
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Barbara
B
Papadopoulou
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Jacques
J
Corbeil
Centre de Recherche en Infectiologie, Centre de Recherche du CHU de Québec, Québec, Canada.
Marc
M
Ouellette
D000222:Adaptation, Physiological / Q000235:genetics; D019295:Computational Biology; D056915:DNA Copy Number Variations; D005784:Gene Amplification; D018503:Genome, Protozoan; D055029:Inverted Repeat Sequences; D007892:Leishmania braziliensis / Q000235:genetics* / Q000378:metabolism; D018314:Leishmania infantum / Q000235:genetics* / Q000378:metabolism; D018320:Leishmania major / Q000235:genetics* / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D013045:Species Specificity; D013269:Stochastic Processes
C435911:RAD51 protein, Leishmania major; D051135:Rad51 Recombinase