Design and construction of a double inversion recombination switch for heritable sequential genetic memory.

Design and construction of a double inversion recombination switch for heritable sequential genetic memory.
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DOI:
10.1371/journal.pone.0002815
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发表时间:
2008-07-30
期刊:
影响因子:
3.7
通讯作者:
Arkin, Adam P.
Arkin, Adam P.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ham, Timothy S.;Lee, Sung K.;Keasling, Jay D.;Arkin, Adam P.

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反转重组元件为生物系统中的计算和信息编码提供了独特的机会。它们提供了编码到DNA序列本身中的不同的二进制状态,使我们能够克服其他生物记忆或逻辑门系统所带来的限制。此外,理论上可以通过在序列中仔细定位重组酶识别位点来创建复杂的顺序逻辑。在这项工作中,我们描述了一个反转开关的设计和合成使用的fim和hin反转重组系统,以创建一个可遗传的顺序存储器开关。我们以重叠的方式集成了两个反转系统,创建了一个可以具有多个状态的开关。开关能够以类似于有限状态机的方式从状态转换到状态,同时将状态信息编码到DNA中。这种开关不需要蛋白质表达来维持其状态,即使在细胞死亡时也能“记住”其状态。我们能够证明过渡到五种可能的状态中的三种,这表明了这种转换的可行性。我们证明,一个可遗传的记忆系统,其状态编码到DNA是可能的,和反转重组系统可能是一个起点,更复杂的记忆电路。虽然电路并没有完全表现出预期的效果,但我们证明了多状态的时间记忆是可以实现的。
Inversion recombination elements present unique opportunities for computing and information encoding in biological systems. They provide distinct binary states that are encoded into the DNA sequence itself, allowing us to overcome limitations posed by other biological memory or logic gate systems. Further, it is in theory possible to create complex sequential logics by careful positioning of recombinase recognition sites in the sequence. In this work, we describe the design and synthesis of an inversion switch using the fim and hin inversion recombination systems to create a heritable sequential memory switch. We have integrated the two inversion systems in an overlapping manner, creating a switch that can have multiple states. The switch is capable of transitioning from state to state in a manner analogous to a finite state machine, while encoding the state information into DNA. This switch does not require protein expression to maintain its state, and “remembers” its state even upon cell death. We were able to demonstrate transition into three out of the five possible states showing the feasibility of such a switch. We demonstrate that a heritable memory system that encodes its state into DNA is possible, and that inversion recombination system could be a starting point for more complex memory circuits. Although the circuit did not fully behave as expected, we showed that a multi-state, temporal memory is achievable.
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期刊: SCIENCE
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