RESUMO
Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
Assuntos
DNA Mitocondrial/genética , Doenças do Cão/genética , Haplótipos , Tumores Venéreos Veterinários/genética , Animais , Cães , Transferência Genética Horizontal , Filogenia , Polimorfismo Genético , Recidiva , Seleção GenéticaRESUMO
The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by "metastasizing" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.
Assuntos
Evolução Clonal/genética , Doenças do Cão/classificação , Doenças do Cão/genética , Tumores Venéreos Veterinários/classificação , Tumores Venéreos Veterinários/genética , Animais , Doenças do Cão/epidemiologia , Cães , Exossomos , Expressão Gênica , Mutagênese , Filogenia , Seleção Genética , Tumores Venéreos Veterinários/epidemiologiaRESUMO
Thirty-six West African Dwarf (WAD) goats were used to assess the effects of an experimental Trypanosoma congolense infection on their reproductive system. Estrous cycles were synchronised and when confirmed pregnant (n = 31), the does were randomly allocated into control and trypanosome-infected groups. After infection, the animals were carefully observed till parturition. Trypanosome infection caused an increase of rectal temperature, a significant drop in PCV (infected: 23.3 +/- 0.3%; control: 28.5 +/- 0.4%; P < 0.0001) and abortions in 27.8% of the infected does. Kids born from infected does had a lower birth weight than kids born from control goats (0.9 +/- 0.1 kg versus 1.6 +/- 0.1 kg; P < 0.0001). Eight out of 13 kids (61.5%) that were born alive from infected does died during their first week of life. Plasma pregnancy-associated glycoprotein (PAG) and progesterone concentrations were lower in the infected animals than in the controls. In general, PAG concentration in does which aborted dropped before abortion. Our results revealed that artificial T. congolense infection affected reproductive performance of WAD goats with abortions, premature births and perinatal losses being observed. Neither transplacental transmission of T. congolense nor histopathological lesions of the placenta could be demonstrated.