Darwinism from Artificial Genomes

十年前，美国国家航空航天局委托美国国家科学院调查已知的生命极限，发展一个关于生命的一般理论，并提出在宇宙中可能发现外星生命的方法。科学院建议将合成生物学作为解决生命科学中这些重大问题的工具。合成生物学超越了描述生物学，后者只研究地球自然历史给我们的一个生命例子。这个项目实施了合成生物学来检验DNA替代品的合理性，DNA是地球上生命遗传的主要单位。该项目还强调公众宣传工作和对早期职业科学家的培训。该项目将提供一种支持达尔文进化论的新型合成化学系统，这符合MCB强调的“合成生物学……捕捉机械、定量和进化方法的力量”。“外来的”达尔文生物聚合物将具有四个信息构建块（PZBS，假设为最佳数量），一个聚电解质骨架（假设为达尔文主义所必需），以及在遗传信息传递中与标准GACT DNA一样的杂环氢键（假设为方向性所必需）。这将是第一个不包含任何自然构建块的达尔文系统的例子。此外，PZBS DNA在沃森-克里克大小互补配对的基础上增加了“瘦”和“胖”配对，具有标准GACT DNA无法获得的信息结构和功能。将化学合成PZBS DNA并对其进行表征。支持PZBS生物聚合物扩增的聚合酶将通过区隔化的自我复制进化。对于测序，将使用转写技术对GACTPZ六字母DNA进行测序；创造性地重新利用这个将测序PZBS DNA。PZBS文库将在选择压力下进化出功能性的PZBS分子。随着PZBS系统的发展，晶体学将贯穿于先进的核酸理论。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

A decade ago, NASA commissioned the National Academy to survey what was known about the limits of life, develop a general theory of life, and suggest ways that alien life might be found in the cosmos. The Academy recommended that synthetic biology be a tool to address such big questions in life science. Synthetic biology goes beyond descriptive biology, which investigates only the one example of life that the natural history on earth has given us. This project implements synthetic biology to examine the plausibility of alternatives to DNA, which is the primary unit of heredity of life on earth. This project also emphasizes a public outreach effort and the training of early career scientists. A novel synthetic chemical system that supports Darwinian evolution will be delivered through this project, which fits the MCB emphasis on "synthetic biology…capturing the power of mechanistic, quantitative, and evolutionary approaches". The "alien" Darwinian biopolymer will have four informational building blocks (PZBS, hypothesized as an optimal number), a polyelectrolyte backbone (hypothesized necessary for Darwinism), and inter-heterocycle hydrogen bonding (hypothesized required for directionality) in the transfer of genetic information as standard GACT DNA does. This will be the first example of a Darwinian system that does not include any natural building blocks. Further, PZBS DNA adds "skinny" and "fat" pairing to Watson-Crick size-complementary pairing, informational structures and functionality unavailable to standard GACT DNA. PZBS DNA will be synthesized chemically and characterized. Polymerases to support PZBS biopolymers amplification will be evolved by compartmentalized self-replication. For sequencing, a transliteration technique to sequence GACTPZ six-letter DNA will be used; creative re-purposing of this will sequence PZBS DNA. PZBS libraries will then be placed under selection pressure to evolve functional PZBS molecules. Crystallography will be applied throughout to advance nucleic acid theory as the PZBS system is advanced.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.