Vertical Cancer Transmission via Asexual Fragmentation and Associated Cancer Prevalence

IF 3.5 2区 生物学 Q1 EVOLUTIONARY BIOLOGY
Jibeom Choi
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Abstract

While sexual reproduction is a general feature of animals, fissiparity and budding are relatively uncommon modes of asexual reproduction by which a fragment from a parent becomes an independent organism. Unlike unitary development, tumor cells can be included in the detached fragment destined to become offspring. Although fragmentation facilitates the vertical transmission of parental tumor cells to nascent progeny, this process requires significantly fewer cell replications than development from a zygote. The former is a risk factor for cancer, while the latter reduces oncogenic mutations during replication, indicating that two opposite effects of carcinogenesis are involved in fragmentation. If fragmentation can significantly reduce the number of cell replications for the development and a small portion of parental cancer is transmitted to the offspring during fragmentation, consecutive fragmentation across generations can gradually diminish the cancer risk of offspring, which I term fragmentational purging. On the other hand, consecutive fragmentation may aggravate the cancer risk of the progeny, a process of fragmentational accumulation. The model results imply that fragmentational purging does not necessarily guarantee the evolution of fragmentation, nor does fragmentational accumulation ensure its exclusion. Other relevant factors including juvenile susceptibility of sexual reproduction and loss of genetic diversity stemming from asexual reproduction can influence the selective advantage of fragmentation. Furthermore, owing to the common features of stemness and self-renewal, the existence of pluripotent adult stem cells required for fragmentation could be coupled with elevated cancer risk. The model results across diverse parameters and the associated mathematical analyses highlight multifaceted evolutionary trajectories toward fragmentation. Further investigation of cancer-suppression strategies that fragmentational animals employ could provide insights into regenerative medicine and cancer therapy.

通过无性分裂的垂直癌症传播和相关的癌症患病率
有性生殖是动物的普遍特征,而分裂和出芽是相对不常见的无性生殖方式,通过这种方式,来自亲本的一个片段成为一个独立的有机体。与单一发育不同,肿瘤细胞可以包含在注定成为后代的分离片段中。尽管碎片化促进了亲代肿瘤细胞向新生后代的垂直传递,但这一过程所需的细胞复制比从受精卵发育所需的细胞复制少得多。前者是癌症的危险因素,而后者在复制过程中减少致癌突变,这表明碎片化涉及两种相反的致癌作用。如果片段化可以显著减少发育过程中细胞的复制次数,并且在片段化过程中有一小部分亲本癌症遗传给后代,那么跨代的连续片段化可以逐渐降低后代的癌症风险,我称之为片段化净化。另一方面,连续的碎片化可能会加重后代的癌症风险,这是一个碎片化积累的过程。模型结果表明,碎片化吹扫并不一定保证碎片化演化,碎片化堆积也不一定保证碎片化的排除。其他相关因素,包括幼鱼有性生殖的易感性和无性生殖导致的遗传多样性的丧失,都可以影响碎片化的选择优势。此外,由于干细胞和自我更新的共同特征,分裂所需的多能成体干细胞的存在可能伴随着癌症风险的增加。模型结果跨越了不同的参数和相关的数学分析,突出了朝向碎片化的多面进化轨迹。进一步研究碎片化动物采用的癌症抑制策略可以为再生医学和癌症治疗提供见解。
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来源期刊
Evolutionary Applications
Evolutionary Applications 生物-进化生物学
CiteScore
8.50
自引率
7.30%
发文量
175
审稿时长
6 months
期刊介绍: Evolutionary Applications is a fully peer reviewed open access journal. It publishes papers that utilize concepts from evolutionary biology to address biological questions of health, social and economic relevance. Papers are expected to employ evolutionary concepts or methods to make contributions to areas such as (but not limited to): medicine, agriculture, forestry, exploitation and management (fisheries and wildlife), aquaculture, conservation biology, environmental sciences (including climate change and invasion biology), microbiology, and toxicology. All taxonomic groups are covered from microbes, fungi, plants and animals. In order to better serve the community, we also now strongly encourage submissions of papers making use of modern molecular and genetic methods (population and functional genomics, transcriptomics, proteomics, epigenetics, quantitative genetics, association and linkage mapping) to address important questions in any of these disciplines and in an applied evolutionary framework. Theoretical, empirical, synthesis or perspective papers are welcome.
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