Torday J S, Rehan V K
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, U.S.
Cell Commun Insights. 2009 Sep 9;2:17-25. doi: 10.4137/cci.s2776.
In the post-genomic era the complex problem of evolutionary biology can be tackled from the top-down, the bottom-up, or from the middle-out. Given the emergent and contingent nature of this process, we have chosen to take the latter approach, both as a mechanistic link to developmental biology and as a rational means of identifying signaling mechanisms based on their functional genomic significance. Using this approach, we have been able to configure a working model for lung evolution by reverse-engineering lung surfactant from the mammalian lung to the swim bladder of fish. Based on this archetypal cell-molecular model, we have reduced evolutionary biology to cell communication, starting with unicellular organisms communicating with the environment, followed by cell-cell communication to generate metazoa, culminating in the communication of genetic information between generations, i.e. reproduction. This model predicts the evolution of physiologic systems-including development, homeostasis, disease, regeneration/repair, and aging- as a logical consequence of biology reducing entropy. This approach provides a novel and robust way of formulating refutable, testable hypotheses to determine the ultimate origins and first principles of physiology, providing candidate genes for phenotypes hypothesized to have mediated evolutionary changes in structure and/or function. Ultimately, it will form the basis for predictive medicine and molecular bioethics, rather than merely showing associations between genes and pathology, which is an unequivocal Just So Story. In this new age of genomics, our reach must exceed our grasp.
在后基因组时代，进化生物学的复杂问题可以从自上而下、自下而上或从中间向外的方式来解决。鉴于这一过程的涌现性和偶然性，我们选择了后一种方法，既作为与发育生物学的机制联系，也作为基于其功能基因组意义来识别信号传导机制的合理手段。运用这种方法，我们得以通过对从哺乳动物肺到鱼类鱼鳔的肺表面活性物质进行逆向工程，构建出一个肺进化的工作模型。基于这个原型细胞 - 分子模型，我们将进化生物学简化为细胞通讯，从单细胞生物与环境的通讯开始，接着是细胞间通讯以产生后生动物，最终是代与代之间遗传信息的通讯，即繁殖。该模型预测生理系统的进化——包括发育、稳态、疾病、再生/修复和衰老——是生物学降低熵的逻辑结果。这种方法提供了一种新颖且强大的方式来提出可证伪、可测试的假设，以确定生理学的最终起源和首要原则，为假设介导了结构和/或功能进化变化的表型提供候选基因。最终，它将成为预测医学和分子生物伦理学的基础，而不仅仅是展示基因与病理学之间的关联，后者不过是一个明确的“就这么回事”的故事。在这个基因组学的新时代，我们的探索必须超越我们的掌控。
