Darwinism from Artificial Genomes

十年前，NASA委托美国国家科学院调查已知的生命极限，发展生命的一般理论，并提出在宇宙中发现外星生命的方法。该学院建议合成生物学成为解决生命科学中如此重大问题的工具。合成生物学超越了描述生物学，后者只研究地球自然历史为我们提供的生命的一个例子。该项目实施了合成生物学，以检验DNA替代品的合理性，DNA是地球上生命遗传的主要单位。该项目还强调公共宣传努力和对早期职业科学家的培训。一个支持达尔文进化论的新的合成化学系统将通过这个项目交付，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”。与标准的GACT DNA一样，“外星”达尔文生物聚合物在遗传信息的传递中将有四个信息构建块(PZBS，假设为最佳数量)、聚电解质主干(假设达尔文学说所必需的)和杂环间氢键(假设为方向性所需)。这将是第一个不包括任何自然构件的达尔文体系的例子。此外，PZBS DNA在Watson-Crick大小的基础上增加了“瘦”和“胖”配对--这是标准GACT DNA所不具备的互补配对、信息结构和功能。将用化学方法合成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分区化的自我复制进化。对于测序，将使用音译技术对GACTPZ六个字母的DNA进行排序；创造性地重新利用这一技术将对PZBS DNA进行排序。然后，PZBS文库将处于选择压力下，以进化出具有功能的PZBS分子。随着PZBS系统的进步，结晶学将被应用于推动核酸理论的发展。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.