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Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial

Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial
Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial
A fatal transmissible tumor spread between individuals by biting has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous marsupial. Here we provide genetic evidence establishing that the tumor is clonal and therefore foreign to host devils. Thus, the disease is highly unusual because it is not just a tumor but also a tissue graft, passed between individuals without invoking an immune response. The MHC plays a key role in immune responses to both tumors and grafts. The most common mechanism of immune evasion by tumors is down-regulation of classical cell surface MHC molecules. Here we show that this mode of immune escape does not occur. However, because the tumor is a graft, it should still be recognized and rejected by the host's immune system due to foreign cell surface antigens. Mixed lymphocyte responses showed a lack of alloreactivity between lymphocytes of different individuals in the affected population, indicating a paucity of MHC diversity. This result was verified by genotyping, providing a conclusive link between a loss of MHC diversity and spread of a disease through a wild population. This novel disease arose as a direct result of loss of genetic diversity and the aggressive behavior of the host species. The neoplastic clone continues to spread although the population, and, without active disease control by removal of affected animals and the isolation of disease-free animals, the Tasmanian devil faces extinction.
conservation genetics, tasmanian devil, wildlife disease, immune evasion
0027-8424
16221-16226
Siddle, Hannah V.
2f0c1307-55d3-4965-a8b0-495c4a799f27
Kreiss, Alexandre
860c2193-1683-44ce-8809-0ac0c8cee2c5
Eldridge, Mark D.B.
cbd54e1d-dd36-4108-91ab-bb9f7d770a3a
Noonan, Erin
1f94cd8e-8273-44f9-b6a3-0336af7a69af
Clarke, Candice J.
b5479bca-05a1-4e5f-8695-e765f414d42e
Pyecroft, Stephen
7a67b462-1c90-40f0-a4d1-881ea2a5b650
Woods, Gregory M.
968c4263-c4c2-49db-b1de-e0c758b88dab
Belov, Katherine
53f3bf11-757e-466d-bc93-8958b7a9dae1
Siddle, Hannah V.
2f0c1307-55d3-4965-a8b0-495c4a799f27
Kreiss, Alexandre
860c2193-1683-44ce-8809-0ac0c8cee2c5
Eldridge, Mark D.B.
cbd54e1d-dd36-4108-91ab-bb9f7d770a3a
Noonan, Erin
1f94cd8e-8273-44f9-b6a3-0336af7a69af
Clarke, Candice J.
b5479bca-05a1-4e5f-8695-e765f414d42e
Pyecroft, Stephen
7a67b462-1c90-40f0-a4d1-881ea2a5b650
Woods, Gregory M.
968c4263-c4c2-49db-b1de-e0c758b88dab
Belov, Katherine
53f3bf11-757e-466d-bc93-8958b7a9dae1

Siddle, Hannah V., Kreiss, Alexandre, Eldridge, Mark D.B., Noonan, Erin, Clarke, Candice J., Pyecroft, Stephen, Woods, Gregory M. and Belov, Katherine (2007) Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proceedings of the National Academy of Sciences, 104 (41), 16221-16226. (doi:10.1073/pnas.0704580104). (PMID:17911263)

Record type: Article

Abstract

A fatal transmissible tumor spread between individuals by biting has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous marsupial. Here we provide genetic evidence establishing that the tumor is clonal and therefore foreign to host devils. Thus, the disease is highly unusual because it is not just a tumor but also a tissue graft, passed between individuals without invoking an immune response. The MHC plays a key role in immune responses to both tumors and grafts. The most common mechanism of immune evasion by tumors is down-regulation of classical cell surface MHC molecules. Here we show that this mode of immune escape does not occur. However, because the tumor is a graft, it should still be recognized and rejected by the host's immune system due to foreign cell surface antigens. Mixed lymphocyte responses showed a lack of alloreactivity between lymphocytes of different individuals in the affected population, indicating a paucity of MHC diversity. This result was verified by genotyping, providing a conclusive link between a loss of MHC diversity and spread of a disease through a wild population. This novel disease arose as a direct result of loss of genetic diversity and the aggressive behavior of the host species. The neoplastic clone continues to spread although the population, and, without active disease control by removal of affected animals and the isolation of disease-free animals, the Tasmanian devil faces extinction.

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e-pub ahead of print date: 2 October 2007
Published date: 9 October 2007
Keywords: conservation genetics, tasmanian devil, wildlife disease, immune evasion
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 362982
URI: http://eprints.soton.ac.uk/id/eprint/362982
ISSN: 0027-8424
PURE UUID: 8d1337d7-89ac-4356-99fb-763fd8bdb4b8

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Date deposited: 18 Mar 2014 16:15
Last modified: 16 Jul 2019 21:10

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Contributors

Author: Alexandre Kreiss
Author: Mark D.B. Eldridge
Author: Erin Noonan
Author: Candice J. Clarke
Author: Stephen Pyecroft
Author: Gregory M. Woods
Author: Katherine Belov

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