文章：

袋獾中两种可传播癌症的演化

The evolution of two transmissible cancers in Tasmanian devils

原文发布日期：2023-04-20

DOI: 10.1126/science.abq6453

类型: Research Article

开放获取: 否

文章简介：

A tale of two cancers

Already threatened by habitat loss and past persecution, Tasmanian devil populations have been decimated over the past few decades by a fatal transmissible cancer referred to as DFT1. Some recent research has suggested that the growth and spread of this cancer has slowed, and it may have become endemic, leading to lower mortality. However, Stammnitz et al. describe the evolution of a second transmissible facial cancer in Tasmanian devils, DFT2. This lineage evolved more recently, mutates more rapidly, and is a high-level threat to this species. —SNV

Abstract

Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analyzing 78 DFT1 and 41 DFT2 genomes relative to a newly assembled, chromosome-level reference. Time-resolved phylogenetic trees reveal that DFT1 first emerged in 1986 (1982 to 1989) and DFT2 in 2011 (2009 to 2012). Subclone analysis documents transmission of heterogeneous cell populations. DFT2 has faster mutation rates than DFT1 across all variant classes, including substitutions, indels, rearrangements, transposable element insertions, and copy number alterations, and we identify a hypermutated DFT1 lineage with defective DNA mismatch repair. Several loci show plausible evidence of positive selection in DFT1 or DFT2, including loss of chromosome Y and inactivation of MGA, but none are common to both cancers. This study reveals the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.

简介翻译： 

两种癌症的故事

塔斯马尼亚袋獾本已受到栖息地丧失和过往迫害的威胁，而在过去几十年里，一种被称为 DFT1 的致命传染性癌症更使其种群数量急剧减少。近期的一些研究表明，这种癌症的生长和传播速度已经放缓，并可能已成为地方性流行，导致死亡率下降。然而，Stammnitz 等人描述了塔斯马尼亚袋獾中第二种传染性面部癌症 DFT2 的演化过程。该谱系出现时间更晚，突变速度更快，对该物种构成了高度威胁。—SNV

摘要

塔斯马尼亚袋獾已衍生出两个传染性癌症谱系，分别命名为袋獾面部肿瘤 1（DFT1）和袋獾面部肿瘤 2（DFT2）。我们通过分析相对于新组装的染色体级别参考基因组的 78 个 DFT1 和 41 个 DFT2 基因组，研究了这些克隆的遗传多样性和演化过程。时间解析系统发育树显示，DFT1 首次出现于 1986 年（1982–1989 年），DFT2 首次出现于 2011 年（2009–2012 年）。亚克隆分析记录了异质性细胞群体的传播。DFT2 在所有变异类别（包括替换、插入缺失、重排、转座元件插入和拷贝数变异）上均比 DFT1 具有更快的突变率，并且我们鉴定出一个具有 DNA 错配修复缺陷的高度突变 DFT1 谱系。数个位点显示出 DFT1 或 DFT2 可能受到正选择的合理证据，包括 Y 染色体丢失和 MGA 基因失活，但两者间不存在共有的选择信号。本研究揭示了在塔斯马尼亚袋獾中共存于同一生态位的两种传染性癌症的平行长期演化。

原文链接：

The evolution of two transmissible cancers in Tasmanian devils