Choi Jibeom
Department of Applied Mathematics Kyung Hee University Yongin Republic of Korea.
School of Computational Sciences Korea Institute for Advanced Study Seoul Republic of Korea.
Evol Appl. 2025 May 21;18(5):e70111. doi: 10.1111/eva.70111. eCollection 2025 May.
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.
虽然有性生殖是动物的普遍特征，但裂体生殖和出芽生殖是相对罕见的无性生殖方式，通过这种方式，亲代的一个片段可成为独立的生物体。与单一发育不同，肿瘤细胞可包含在注定成为后代的分离片段中。尽管分裂促进了亲代肿瘤细胞向新生后代的垂直传播，但这一过程所需的细胞复制比从受精卵发育要少得多。前者是癌症的一个风险因素，而后者在复制过程中减少了致癌突变，这表明致癌作用的两种相反效应与分裂有关。如果分裂能显著减少发育所需的细胞复制数量，并且在分裂过程中有一小部分亲代癌症传递给后代，那么跨代的连续分裂可以逐渐降低后代的癌症风险，我将此称为分裂清除。另一方面，连续分裂可能会加剧后代的癌症风险，即分裂积累的过程。模型结果表明，分裂清除不一定能保证分裂的进化，分裂积累也不一定能确保其被排除。包括有性生殖的幼年易感性和无性生殖导致的遗传多样性丧失等其他相关因素，会影响分裂的选择优势。此外，由于干性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与癌症风险升高相关。跨越不同参数的模型结果及相关数学分析突出了分裂的多方面进化轨迹。对采用分裂方式的动物所使用的癌症抑制策略进行进一步研究，可能会为再生医学和癌症治疗提供见解。
