Comparative Cytogenetic Mapping and Telomere Analysis Provide Evolutionary Predictions for Devil Facial Tumour 2.

Emory D Ingles,Janine E Deakin

doi:10.3390/genes11050480

Abstract

The emergence of a second transmissible tumour in the Tasmanian devil population, devil facial tumour 2 (DFT2), has prompted questions on the origin and evolution of these transmissible tumours. We used a combination of cytogenetic mapping and telomere length measurements to predict the evolutionary trajectory of chromosome rearrangements in DFT2. Gene mapping by fluorescence in situ hybridization (FISH) provided insight into the chromosome rearrangements in DFT2 and identified the evolution of two distinct DFT2 lineages. A comparison of devil facial tumour 1 (DFT1) and DFT2 chromosome rearrangements indicated that both started with the fusion of a chromosome, with potentially critically short telomeres, to chromosome 1 to form dicentric chromosomes. In DFT1, the dicentric chromosome resulted in breakage–fusion–bridge cycles leading to highly rearranged chromosomes. In contrast, the silencing of a centromere on the dicentric chromosome in DFT2 stabilized the chromosome, resulting in a less rearranged karyotype than DFT1. DFT2 retains a bimodal distribution of telomere length dimorphism observed on Tasmanian devil chromosomes, a feature lost in DFT1. Using long term cell culture, we observed homogenization of telomere length over time. We predict a similar homogenization of telomere lengths occurred in DFT1, and that DFT2 is unlikely to undergo further substantial rearrangements due to maintained telomere length.

Highlights

Devil facial tumour disease (DFT1) was first detected by a photographer in 1996 in north easternTasmania [1]
We investigated devil facial tumour 2 (DFT2) evolution in two ways, firstly by comparing gene order on DFT2 chromosomes from four different tumours and secondly by examining telomere length after 200 population doublings in vitro
The translocated chromosome 6 has undergone at least two inversions during the evolution of DFT2 (Figure 1), the chromosome has not experienced the extensive rearrangement observed on the chromosome derived from an end-to-end fusion of chromosomes 1 and X in devil facial tumour 1 (DFT1)

Summary

Introduction

Devil facial tumour disease (DFT1) was first detected by a photographer in 1996 in north easternTasmania [1]. Devil facial tumour disease (DFT1) was first detected by a photographer in 1996 in north eastern. Areas affected by DFT1 are estimated to have experienced roughly an 80% decline in Tasmanian devil population numbers [2]. As opposed to being transmitted by an infectious pathogen such as virus or bacterium, it is the cancer cells themselves which are transmitted [3]. This occurs as a side effect of Tasmanian devil social behaviour, who will often bite each other, allowing the cancer cells to transmit into open wounds [4] and thereafter growing into a new tumour. Transmitted cells are able to grow undetected by the host’s immune system, attributed in part to a downregulation of Major

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