Dataset Information

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

ABSTRACT: Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.

SUBMITTER: Strakova A

PROVIDER: S-EPMC4869914 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Strakova Andrea A Ní Leathlobhair Máire M Wang Guo-Dong GD Yin Ting-Ting TT Airikkala-Otter Ilona I Allen Janice L JL Allum Karen M KM Bansse-Issa Leontine L Bisson Jocelyn L JL Castillo Domracheva Artemio A de Castro Karina F KF Corrigan Anne M AM Cran Hugh R HR Crawford Jane T JT Cutter Stephen M SM Delgadillo Keenan Laura L Donelan Edward M EM Faramade Ibikunle A IA Flores Reynoso Erika E Fotopoulou Eleni E Fruean Skye N SN Gallardo-Arrieta Fanny F Glebova Olga O Häfelin Manrique Rodrigo F RF Henriques Joaquim Jgp JJ Ignatenko Natalia N Koenig Debbie D Lanza-Perea Marta M Lobetti Remo R Lopez Quintana Adriana M AM Losfelt Thibault T Marino Gabriele G Martincorena Inigo I Martínez Castañeda Simón S Martínez-López Mayra F MF Meyer Michael M Nakanwagi Berna B De Nardi Andrigo B AB Neunzig Winifred W Nixon Sally J SJ Onsare Marsden M MM Ortega-Pacheco Antonio A Peleteiro Maria C MC Pye Ruth J RJ Reece John F JF Rojas Gutierrez Jose J Sadia Haleema H Schmeling Sheila K SK Shamanova Olga O Ssuna Richard K RK Steenland-Smit Audrey E AE Svitich Alla A Thoya Ngoka Ismail I Vițălaru Bogdan A BA de Vos Anna P AP de Vos Johan P JP Walkinton Oliver O Wedge David C DC Wehrle-Martinez Alvaro S AS van der Wel Mirjam G MG Widdowson Sophie Ae SA Murchison Elizabeth P EP

eLife 20160517

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions tr ...[more]

PMID: 27185408

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Project description:BackgroundEvolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations.ResultsWe sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47%) of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently.ConclusionOur demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of these genes is not? This phenomenon may be related to the nature of their ligands and their importance in everyday life.

Project description:To achieve proper diagnosis of dogs based on acute clinical symptoms and poorly preserved field samples taken from animals that died due to canine distemper (CD), a new differential diagnostic test has been developed based on polymerase chain reaction (PCR). In this study, more than 150 samples collected from dogs showing respiratory, gastrointestinal and neurological signs suggesting canine distemper virus (CDV) infection were examined. The samples consisted of urine, blood and nasal swabs collected from clinically ill patients, sent to our laboratory by clinicians from various veterinary clinics throughout Hungary. Various organs collected during the necropsy of dogs with pathological changes that suggested CDV infection were also included. Three distinct PCRs were designed. For diagnostic purposes, a primer pair specific to a 409 bases-long segment within the conservative part of the large polymerase region (L) of the CDV genome was designed. Using this test, out of the 150 analyzed samples, 46 (30.66%) proved to be positive for CDV, indicating that CDV still represents a high risk to the canine population in Hungary. For the phylogenetical analysis, a primer pair that completely encompasses the hemagglutinin (H) gene of the CDV genome was designed. The amplicons of this region were sequenced in both directions using the appropriate primers. Our results indicate that several different CDV genotypes are currently present in Hungary. Nine of the analyzed Hungarian strains turned out to belong to the so-called Arctic group of CDVs, and were most closely related to non-European strains from North America, China and Greenland, as well as to the phocine distemper virus 2 (PDV-2) isolated from Baikal seals (Phoca sibirica). One of the Hungarian strains showed high similarity to other European isolates from Denmark, Germany, Italy and Turkey, as well as to other isolates from geographically more distant regions, such as the USA. Three Hungarian strains seem to join a new cluster that is formed by only a couple of strains, one isolated from a mink in Denmark, and another from a dog in North America. Using a third set of primers, a restriction fragment length polymorphism (RFLP) assay has also been designed for the fast and reliable differentiation of the wild-type CDVs from the vaccine strains.

Dataset Information

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Publications

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

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