title: Comparative genomic analysis of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis.
abstract: BACKGROUND
  The Leishmania (Viannia) braziliensis complex is responsible for most cases of New World tegumentary leishmaniasis. This complex includes two closely related species but with different geographic distribution and disease phenotypes, L. (V.) peruviana and L. (V.) braziliensis. However, the genetic basis of these differences is not well understood and the status of L. (V.) peruviana as distinct species has been questioned by some. Here we sequenced the genomes of two L. (V.) peruviana isolates (LEM1537 and PAB-4377) using Illumina high throughput sequencing and performed comparative analyses against the L. (V.) braziliensis M2904 reference genome. Comparisons were focused on the detection of Single Nucleotide Polymorphisms (SNPs), insertions and deletions (INDELs), aneuploidy and gene copy number variations.
  
  
  RESULTS
  We found 94,070 variants shared by both L. (V.) peruviana isolates (144,079 in PAB-4377 and 136,946 in LEM1537) against the L. (V.) braziliensis M2904 reference genome while only 26,853 variants separated both L. (V.) peruviana genomes. Analysis in coding sequences detected 26,750 SNPs and 1,513 indels shared by both L. (V.) peruviana isolates against L. (V.) braziliensis M2904 and revealed two L. (V.) braziliensis pseudogenes that are likely to have coding potential in L. (V.) peruviana. Chromosomal read density and allele frequency profiling showed a heterogeneous pattern of aneuploidy with an overall disomic tendency in both L. (V.) peruviana isolates, in contrast with a trisomic pattern in the L. (V.) braziliensis M2904 reference. Read depth analysis allowed us to detect more than 368 gene expansions and 14 expanded gene arrays in L. (V.) peruviana, and the likely absence of expanded amastin gene arrays.
  
  
  CONCLUSIONS
  The greater numbers of interspecific SNP/indel differences between L. (V.) peruviana and L. (V.) braziliensis and the presence of different gene and chromosome copy number variations support the classification of both organisms as closely related but distinct species. The extensive nucleotide polymorphisms and differences in gene and chromosome copy numbers in L. (V.) peruviana suggests the possibility that these may contribute to some of the unique features of its biology, including a lower pathology and lack of mucosal development.
authors.affiliation: Laboratório de Imunologia e Genômica de Parasitos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. hvalrod@hotmail.com.|Department of Parasitology, U.S. Naval Medical Research Unit No. 6, Lima, Peru. hvalrod@hotmail.com.
authors.forename: Hugo O
authors.initials: HO
authors.lastname: Valdivia
authors.affiliation: Laboratório de Imunologia e Genômica de Parasitos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. jaumlrc@yahoo.com.br.
authors.forename: João L
authors.initials: JL
authors.lastname: Reis-Cunha
authors.affiliation: Laboratório de Imunologia e Genômica de Parasitos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. gab.luiz@gmail.com.
authors.forename: Gabriela F
authors.initials: GF
authors.lastname: Rodrigues-Luiz
authors.affiliation: Laboratório de Imunologia e Genômica de Parasitos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. rodrigopbaptista@gmail.com.
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Baptista
authors.affiliation: Department of Parasitology, U.S. Naval Medical Research Unit No. 6, Lima, Peru. christian.baldeviano@med.navy.mil.
authors.forename: G Christian
authors.initials: GC
authors.lastname: Baldeviano
authors.affiliation: Department of Parasitology, U.S. Naval Medical Research Unit No. 6, Lima, Peru. robert.gerbassi@med.navy.mil.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gerbasi
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA. ddobson@wusm.wustl.edu.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Dobson
authors.affiliation: Centre Hospitalier Universitaire de Montpellier, Departement de Parasitologie-Mycologie, Centre National de Reference des Leishmanioses, Montpellier, France. f-pratlong@chu-montpellier.fr.
authors.forename: Francine
authors.initials: F
authors.lastname: Pratlong
authors.affiliation: Centre Hospitalier Universitaire de Montpellier, Departement de Parasitologie-Mycologie, Centre National de Reference des Leishmanioses, Montpellier, France. p-bastien@chu-montpellier.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bastien
authors.affiliation: Department of Parasitology, U.S. Naval Medical Research Unit No. 6, Lima, Peru. willy.lescano@med.navy.mil.|Universidad Peruana Cayetano Heredia, School of Public Health and Management, Lima, Peru. willy.lescano@med.navy.mil.
authors.forename: Andrés G
authors.initials: AG
authors.lastname: Lescano
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA. beverley@wusm.wustl.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley
authors.affiliation: Laboratório de Imunologia e Genômica de Parasitos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. daniella@icb.ufmg.br.
authors.forename: Daniella C
authors.initials: DC
authors.lastname: Bartholomeu
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics; D023281:Genomics; D007891:Leishmania / Q000235:genetics*; D007892:Leishmania braziliensis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics