Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer

Elizabeth P Murchison ,John Marshall,Alexandre Kreiss,Fengtang Yang,Niall Gormley,Beiyuan Fu,Irina Khrebtukova,Zhihao Ding,Zoya Kingsbury,Zemin Ning,Sergii Ivakhno,Jennifer Becq,Geoffrey Smith,Simon White,Philip Tedder,Anne-Maree Pearse,Shujun Luo,William Cheng,Bronwen Aken,Isabelle Rasolonjatovo,Yong Gu,Lisa Murray,Mark Kowarsky,Carolyn Tregidgo,Sean Humphray,Keiran Raine,Anthony T Papenfuss ,Anthony J Cox ,Zhiping Feng ,Ludmil B Alexandrov ,Kevin P Hall ,Russell Grocock ,Thomas R Connor ,P Andrew Futreal ,Dirk Evers ,Matthew M Hims ,Ole Schulz-Trieglaff ,Graham R Bignell ,Caitlin M Stewart ,Bee Ling Ng ,Simon R Harris ,David J Mcbride ,Nigel P Carter ,Wendy S W Wong ,David Bentley ,Amber E Alsop ,R Keira Cheetham ,Richard J Shaw ,Peter J Campbell ,Gregory M Woods ,Albert J Vilella ,Gary P Schroth ,Markus Bauer ,David C Wedge ,Stephen M J Searle ,Michael R Stratton

doi:10.1016/j.cell.2011.11.065

Abstract

SummaryThe Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.PaperClip

Highlights

Cancers are clonal cell lineages that arise due to somatic changes that promote cell proliferation and survival
Tasmanian devil facial tumor disease (DFTD) is an unusual cancer that has survived beyond the death of the individual that spawned it by acquiring adaptations for transmission between hosts
The genomes of the Tasmanian devil and its transmissible cancer, DFTD, are of interest both from the perspective of conservation of a threatened species as well as for the insights they may provide into the origins, somatic evolution and population genetics of an extraordinarily divergent neoplastic clonal lineage

Summary

Introduction

Cancers are clonal cell lineages that arise due to somatic changes that promote cell proliferation and survival. Tasmanian devil facial tumor disease (DFTD) is an unusual cancer that has survived beyond the death of the individual that spawned it by acquiring adaptations for transmission between hosts. This cancer has spread through the Tasmanian devil population and is threatening the species with extinction (Hawkins et al, 2006; McCallum et al, 2009). The genomes of the Tasmanian devil and its transmissible cancer, DFTD, are of interest both from the perspective of conservation of a threatened species as well as for the insights they may provide into the origins, somatic evolution and population genetics of an extraordinarily divergent neoplastic clonal lineage. The species has limited genetic diversity, three genetically distinct geographically defined subpopulations have been described (Jones et al, 2004; Miller et al, 2011)

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Discussion

Conclusion