Genome-wide stochastic adaptive DNA amplification at direct and inverted DNA repeats in the parasite Leishmania

• Published in: PLoS biology Vol. 12; no. 5; p. e1001868
• Main Authors: Ubeda, Jean-Michel, Raymond, Frédéric, Mukherjee, Angana, Plourde, Marie, Gingras, Hélène, Roy, Gaétan, Lapointe, Andréanne, Leprohon, Philippe, Papadopoulou, Barbara, Corbeil, Jacques, Ouellette, Marc
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2014; Public Library of Science (PLoS)
• Subjects: Adaptation, Physiological - genetics; Bioinformatics; Biology and Life Sciences; Cloning; Computational Biology; Deoxyribonucleic acid; DNA; DNA Copy Number Variations; DNA sequencing; Experiments; Gene Amplification; Genetic aspects; Genetic research; Genome, Protozoan; Genome-wide association studies; Genomes; Inverted Repeat Sequences; Leishmania; Leishmania braziliensis - genetics; Leishmania braziliensis - metabolism; Leishmania infantum - genetics; Leishmania infantum - metabolism; Leishmania major - genetics; Leishmania major - metabolism; Medicine and Health Sciences; Microbiological research; Molecular weight; Nucleotide sequencing; Parasites; Population; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; Repetitive Sequences, Nucleic Acid; Species Specificity; Stochastic Processes
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1001868

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.