Beyond Center for Fundamental Concepts in Science, Arizona State University, Tempe, AZ 85287, USA.
Phys Biol. 2011 Feb;8(1):015001. doi: 10.1088/1478-3975/8/1/015001. Epub 2011 Feb 7.
The genes of cellular cooperation that evolved with multicellularity about a billion years ago are the same genes that malfunction to cause cancer. We hypothesize that cancer is an atavistic condition that occurs when genetic or epigenetic malfunction unlocks an ancient 'toolkit' of pre-existing adaptations, re-establishing the dominance of an earlier layer of genes that controlled loose-knit colonies of only partially differentiated cells, similar to tumors. The existence of such a toolkit implies that the progress of the neoplasm in the host organism differs distinctively from normal Darwinian evolution. Comparative genomics and the phylogeny of basal metazoans, opisthokonta and basal multicellular eukaryotes should help identify the relevant genes and yield the order in which they evolved. This order will be a rough guide to the reverse order in which cancer develops, as mutations disrupt the genes of cellular cooperation. Our proposal is consistent with current understanding of cancer and explains the paradoxical rapidity with which cancer acquires a suite of mutually-supportive complex abilities. Finally we make several predictions and suggest ways to test this model.
大约 10 亿年前与多细胞生物共同进化的细胞合作基因,也是导致癌症的基因。我们假设癌症是一种返祖现象,当遗传或表观遗传功能障碍解锁了一个古老的“工具包”,重新建立了早期控制松散连接的部分分化细胞的基因的主导地位时,就会发生这种现象,类似于肿瘤。这种工具包的存在意味着肿瘤在宿主生物体内的进展与正常的达尔文进化有明显的不同。比较基因组学和基础后生动物、后口动物和基础多细胞真核生物的系统发生,应该有助于识别相关基因,并确定它们的进化顺序。这个顺序将是癌症发展的大致逆序的粗略指南,因为突变会破坏细胞合作的基因。我们的建议与目前对癌症的理解一致,并解释了癌症获得一系列相互支持的复杂能力的速度之快,令人费解。最后,我们提出了一些预测,并建议了几种测试该模型的方法。