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癌症是杀死个体以拯救物种吗?

Does cancer kill the individual and save the species?

作者信息

Sommer S S

出版信息

Hum Mutat. 1994;3(2):166-9. doi: 10.1002/humu.1380030214.

Abstract

I have argued that most germline mutations are due to endogenous process. I speculate that endogenous control of germline mutation serves an important biological function. A certain rate of mutation is required to generate sufficient variation for adaptation during evolutionary time. Sexual reproduction and recombination may serve to enhance variation, but ultimately new germline mutation is required to replenish variant alleles lost secondary to negative selection, genetic drift, and population bottlenecks. Unfortunately, the requisite mutation rates carry a terrible price: for each advantageous mutation, there are many disadvantageous ones. Thus, all mammals are plagued with substantial Mendelian and multifactorial disease. Consequently, the optimal mutation rate should be at a level just sufficient to maintain the requisite variation needed for adaptation. In this view, mechanisms for negative selection are necessary to keep the mutation rate in check. If a high germline mutation rate produces a high mutation rate in somatic tissues, cancer may be an important mediator of negative selection. The multiple mutations necessary to produce cancer serve to amplify relatively small differences in the mutation rate, thereby providing an efficient selection against individuals with germline mutations that result in a high mutation rate. This hypothesis can account for the general similarity of the longevity-corrected cancer incidence profile and the small but significant prevalence of cancer before and during the reproductive period. While this hypothesis must presently be viewed as speculative, it integrates certain previously disjointed observations and suggests an alternative to the general assumption that cancer represents a breakdown in normal physiology.

摘要

我认为大多数生殖系突变是由内源性过程引起的。我推测生殖系突变的内源性控制具有重要的生物学功能。在进化过程中,需要一定的突变率来产生足够的变异以实现适应。有性生殖和重组可能有助于增加变异,但最终需要新的生殖系突变来补充因负选择、遗传漂变和种群瓶颈而丢失的变异等位基因。不幸的是,所需的突变率付出了惨痛的代价:对于每一个有利突变,都有许多不利突变。因此,所有哺乳动物都受到大量孟德尔和多因素疾病的困扰。因此,最佳突变率应处于刚好足以维持适应所需的必要变异的水平。从这个角度来看,负选择机制对于控制突变率是必要的。如果高生殖系突变率导致体细胞组织中出现高突变率,那么癌症可能是负选择的重要调节因子。产生癌症所需的多个突变有助于放大突变率中相对较小的差异,从而有效地筛选出具有导致高突变率的生殖系突变的个体。这一假设可以解释寿命校正后的癌症发病率概况与生殖期之前和期间癌症的低但显著的患病率之间的总体相似性。虽然目前必须将这一假设视为推测性的,但它整合了某些先前不相关的观察结果,并提出了一种替代普遍假设的观点,即癌症代表正常生理功能的崩溃。

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