The evolution of two transmissible cancers in Tasmanian devils

Area of Science:

• Genomics
• Evolutionary Biology
• Cancer Research

Background:

• Tasmanian devils face extinction due to two transmissible cancers: devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2).
• Understanding the genetic diversity and evolution of these contagious cancers is crucial for conservation efforts.

Purpose of the Study:

• To investigate the genetic diversity and evolutionary trajectories of DFT1 and DFT2.
• To compare mutation rates and identify selection pressures acting on these transmissible cancers.

Main Methods:

• Analysis of 78 DFT1 and 41 DFT2 genomes using a new chromosome-level reference.
• Time-resolved phylogenetic analysis to estimate emergence dates.
• Subclone analysis to assess population heterogeneity and mutation rates.

Main Results:

• DFT1 emerged in 1986 (1982-1989) and DFT2 in 2011 (2009-2012).
• DFT2 exhibits higher mutation rates than DFT1 across all variant classes.
• A hypermutated DFT1 lineage with defective DNA mismatch repair was identified.
• Evidence of positive selection was found at specific loci, including Y chromosome loss and MGA inactivation, but these were not common to both cancers.

Conclusions:

• DFT1 and DFT2 demonstrate parallel long-term evolution despite distinct origins and genetic characteristics.
• The findings provide insights into the evolutionary dynamics of contagious cancers within a single host population.