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.

A third of the world rabies burden is in India. The Sikkim Anti-Rabies and Animal Health (SARAH) program is the first state-wide rabies program in India and demonstrates a successful One Health model of dog-mediated rabies elimination. The SARAH program was created in 2006 as a collaboration between the Government of Sikkim and international non-government organizations—Vets Beyond Borders and Fondation Brigitte Bardot. Activities are directed to canine rabies vaccination, humane dog population control, community education, and treatment of sick and injured animals. In 2005, there were 0.74 human rabies deaths per 100,000 (4 deaths) within Sikkim, and from 2006 to 2015, there were no human rabies deaths. In 2016, two human rabies deaths were reported near the West Bengal border region. From 2005 to 2010, the incidence of animal rabies is unknown; from 2010 to 2016, eight cases of animal rabies were reported. Major challenges for the program are continued commitment to rabies control in the face of 0 to low human rabies incidence and the risk of rabies incursions. Effective intersectoral communication between Health, Veterinary, Forestry, and Police officers is essential to enable rapid response to animal bite incidents and possible rabies incursions. An integrated One Health approach needs to be maintained with enhanced active rabies surveillance. Other states must establish similar programs if India is ever to achieve a goal of eliminating dog-mediated human rabies.

The ICC estimates presented in this study will aid in designing cluster-based studies evaluating educational interventions as part of disease control programs. This study demonstrates the likely benefits of educational intervention incorporating bite prevention and rabies education.

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.