人类和蝙蝠基因组在COSMIC突变特征下的强度
Joon-Hyun Song1,2, Ying Zeng3, Liliana M Dávalos4,5
1Stony Brook Cancer Center, Stony Brook Medicine, Stony Brook University, Stony Brook, NY, USA.
bioRxiv : the preprint server for biology
|September 24, 2024
概括
人类基因组对APOBEC突变表现出了显著的强度,这些突变与癌症和衰老有关. 这种弹性,特别是对C-to-T变化的弹性,突出显示了对这些变异原体的进化防御.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 癌症研究 癌症研究
背景情况:
- 致癌包括在微环境中固定表型的突变.
- 细胞表现出对突变性压力因素的强度,以保持健康.
研究的目的:
- 开发和应用一个模拟管道来评估基因和细胞对变异原体的强度.
- 研究基因组对各种突变特征的强度,特别是APOBEC.
主要方法:
- 开发了Sinabro,一个用于单基替代的序列突变模拟器.
- 在模拟突变发生过程中创建了一个管道来测量基因和细胞强度.
- 对41个突变特征分析了超过7万个序列.
主要成果:
- 发现了人类基因组对APOBEC突变特征SBS2.2的显著稳定性.
- 观察到对导致C-to-T (G-to-A) 突变的签名具有更高的弹性.
- 发现 GC 含量在子的摇摆位置影响了强度,有利于过渡突变.
结论:
- APOBEC在衰老和癌症中的作用是显著的,在人类基因组中进化了对策.
- 寿命较长的蝙蝠比寿命较短的蝙蝠具有更大的APOBEC强度.
- 提供了人类和蝙蝠基因组对抗衰老和癌症相关变异原体的强度的基线.
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