Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra.
Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra.
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DOI：
10.7554/elife.82558
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发表时间：
2022-12-08
期刊：
影响因子：
7.7
通讯作者：
Lynch VJ
中科院分区：
文献类型：
--
作者：
Vazquez JM;Pena MT;Muhammad B;Kraft M;Adams LB;Lynch VJ
在物种中，患癌症的风险与体型和寿命相关，但在物种之间，癌症与体型或寿命之间没有相关性，这表明体型大、寿命长的物种进化出了增强的癌症保护机制。先前我们发现，一些大型的非猿类进化降低了内在的癌症风险，特别是大象及其已灭绝的亲戚（长鼻猿），这与肿瘤抑制基因的普遍复制相一致（Vazquez和Lynch， 2021）。出乎意料的是，我们还发现Xenarthrans（树懒、犰狳和食蚁兽）进化出了非常低的内在癌症风险。在这里，我们表明：(1)几个异种人谱系独立地进化出了更大的身体、更长的寿命和更低的内在癌症风险；(2) Xenarthra和Pilosa茎系的肿瘤风险降低与肿瘤抑制基因重复的爆发一致；(3)在极低剂量的DNA损伤剂作用下，树懒细胞增殖极慢，Xenarthran细胞诱导凋亡；(4)异种犰狳的癌症患病率极低，犰狳几乎没有癌症。这些数据暗示了肿瘤抑制基因的复制在Xenarthrans显著的体型和癌症风险降低的进化过程中，并表明它们是一种显著的抗癌哺乳动物群体。
The risk of developing cancer is correlated with body size and lifespan within species, but there is no correlation between cancer and either body size or lifespan between species indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Previously we showed that several large bodied Afrotherian lineages evolved reduced intrinsic cancer risk, particularly elephants and their extinct relatives (Proboscideans), coincident with pervasive duplication of tumor suppressor genes (Vazquez and Lynch, 2021). Unexpectedly, we also found that Xenarthrans (sloths, armadillos, and anteaters) evolved very low intrinsic cancer risk. Here, we show that: (1) several Xenarthran lineages independently evolved large bodies, long lifespans, and reduced intrinsic cancer risk; (2) the reduced cancer risk in the stem lineages of Xenarthra and Pilosa coincided with bursts of tumor suppressor gene duplications; (3) cells from sloths proliferate extremely slowly while Xenarthran cells induce apoptosis at very low doses of DNA damaging agents; and (4) the prevalence of cancer is extremely low Xenarthrans, and cancer is nearly absent from armadillos. These data implicate the duplication of tumor suppressor genes in the evolution of remarkably large body sizes and decreased cancer risk in Xenarthrans and suggest they are a remarkably cancer-resistant group of mammals.