Could junk DNA be a key to unlock biocomputing?
Dr. Alan Herbert of InsideOutBio describes a pioneering approach to biocomputing
Dr. Alan Herbert, a distinguished genetics scientist formerly with Merck, has just released a paper that asks what if our genome was far smarter than everyone previously believed? What if in the many DNA repeat elements lay the foundation for building a novel type of biocomputer? This approach would enable calculations performed with self-renewing wetware rather than stone-cold hardware, opening the door to logic circuits based on DNA that flips from one state to another, analogous to the way silicon switches “on” and “off.”
How might this kind of DNA computer work?
Simple repeats are called that because the DNA sequence repeats itself over and over again a number of times. The repeats actually are great for building DNA structures with useful properties. Instead of the everyday B-DNA described by Watson and Crick, repeats of certain DNA sequences can morph into some rather exotic higher-energy 3D structures. They can form left-handed duplexes, three-stranded triplexes, and four-stranded quadruplexes. The different DNA structures change how information is read out from DNA to make RNA.
Those repeat sequences that are able to switch from one DNA structure to another are called flipons. Collectively, Dr. Herbert refer to these flipons and their associated functionality as fliponware. Fliponware sets the stage for a cell to make the right wetware tools and run the right genetic program to get the job at hand done. It allows assembly of gene pieces into different RNA-based programs for a cell to overcome challenges from its environment.
Dr. Herbert provides examples of how flipons can be used to create genetic programs, describing ways they can be wired into the logic gates that computers need to function. The flipon logic gates can perform 'AND' or 'NOT' operations. Many can be combined to perform the Boolean operations essential to a universal computer as first described by Turing. Their use in the genome for logical operations resembles how Turing machines work, but instead of a Turing tape, the cell uses RNA to record the results. The series of processing steps decides whether the RNA message is stable or not and the genetic program to execute.
Turning a flipon ON or OFF is possible in many different ways. For example, just stretching the DNA can cause flipons to morph, or they can flip due to a change in temperature or variations in salt concentration.
DNA encode flipons can clearly have a great impact on the way our cells respond to their environment and to diseases like cancer. This new understanding offers hope for novel, targeted, individual therapies in modern medicine, taking us one step closer to truly personalized medicine.
Fliponware has several immediate applications:
Therapeutic applications (target drugs to flipon states that enable cancers or inflammatory diseases)
Biosensors (to detect environmental changes)
Persistent DNA memory (exploiting the extreme stability of quadruplexes after they form)
Cellular switches (change of output in response to a change of input)
Novel DNA nano-architectures (the 3D structure formed depends on flipon state)
“I expect that soon there will be many exciting and beneficial applications for fliponware. Simple sequences are not your grandparent’s junk—instead they are like the rules of thumb that simplify life, acquired over many years of evolution.”
