Pearson B J, Sánchez Alvarado A
Howard Hughes Medical Institute, Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Cold Spring Harb Symp Quant Biol. 2008;73:565-72. doi: 10.1101/sqb.2008.73.045. Epub 2009 Jan 15.
All multicellular organisms have requirements for tumor suppression to regulate cellular proliferation during either embryonic development or adult life. However, different organisms have vastly different requirements. Adult tumor suppression is probably not crucial to organisms possessing both short life spans and largely postmitotic soma. In contrast, animals with lifelong tissue turnover or those capable of regenerating body parts lost to injury must possess evolutionarily selected mechanisms to control rates of cell proliferation such that tissue homeostasis can be maintained or restored after injury. We hypothesize that these biological differences may help to explain why the lists of tumor suppressor genes in humans and Drosophila are largely nonoverlapping. Here, we address this disparity by examining the tumor suppressor gene content of two outgroups to the vertebrates and flies/nematodes: the freshwater planarian and the single-celled choanoflagellate. Both of these organisms have recently had their genomes sequenced, giving us a first glimpse of which known tumor suppressor genes have been maintained during evolution. In addition, we attempt to resolve which genes may have had ancestral tumor suppressor function and which may have acquired this function de novo.
所有多细胞生物在胚胎发育或成年期都需要肿瘤抑制来调节细胞增殖。然而,不同的生物有截然不同的需求。对于寿命短且体细胞大多不再分裂的生物来说,成年期的肿瘤抑制可能并不关键。相比之下,具有终身组织更新能力或能够再生因受伤而缺失的身体部位的动物,必须拥有经过进化选择的机制来控制细胞增殖速率,以便在受伤后能够维持或恢复组织稳态。我们推测,这些生物学差异可能有助于解释为什么人类和果蝇的肿瘤抑制基因列表大多没有重叠。在这里,我们通过研究脊椎动物和果蝇/线虫这两个外类群的两个物种——淡水涡虫和单细胞领鞭毛虫的肿瘤抑制基因含量来解决这一差异。这两种生物最近都完成了基因组测序,让我们首次得以了解哪些已知的肿瘤抑制基因在进化过程中得以保留。此外,我们试图确定哪些基因可能具有祖传的肿瘤抑制功能,哪些可能是从头获得这一功能的。