Replication, Replication, Replication I

This post and the one below it are linked. Here, I discuss a topic that interests us as a group, and below I look at some recent related papers. This post should make reasonable sense in isolation, the second perhaps less so.

Replication is at the heart of biology; whole organisms, cells and molecules all produce copies of themselves. Understanding natural self-replicating systems, and designing our own artificial analogues, is an obvious goal for scientists - many of whom share dreams of explaining the origin of life, or creating new, synthetic living systems.

Molecular-level replication is a natural place to start, since it is (in principle) the simplest, and also a necessary component of larger-scale self-replicating systems. The most obvious example in nature is the copying of DNA; prior to cell division, a single copy of the entire sequence of base pairs in the genome must be produced. But the processes of transcription (in which the information in DNA sequence is copied into an RNA sequence) and translation (in which the information in RNA sequence is copied into protein sequence) are closely related to replication. The information initially present in the DNA sequence is simply written out in a new medium, like printing off a copy of an electronic document. This process is illustrated in the figure above (which I stole from here). This figure nicely emphasies the polymer sequences (shown as letters) that are being copied into a new medium (note: three RNA bases get copied into one amino acid in a protein: AUG into M, for example). An absolutely fundamental feature of both replication and copying processes is that the copy, once produced, is physically separated from the template from which it was produced. This is important, otherwise the copies couldn't fulfill their function, and more copies could not be made from the same template.

This single fact - that useful copies must separate from their template yet retain the copied information - makes the whole engineering challenge far harder. It's (reasonably) straight-forward to design a complex (bio)chemical system that assembles on top of a template, guided by that template. All you need are sufficiently selective attractive interactions between copy components and the template. But if you then want to separate your copy from the template, these very same attractive interactions work against you, holding the copy in place - and more accurate copies hold on to the template more tightly. My collaborators and I formalise this idea, and explore some of the other consequences of needing to separate copies from templates, in this recent paper.

Largely because of this problem, no-one has yet constructed a purely chemically driven, artificial system that produces copies of long polymers, as nature does. Instead, it has proved necessary to perform external operations such as successively heating and cooling the system. Copies can then grow on the template at low temperature, and then fall off at high temperature, allowing a new copy to be made when the system is cooled down. This is exactly what is done in the PCR, an incredibly important process for amplifying a small amount of DNA in areas ranging from forensics to medicine.

As a group, we're very interested in how copying/replication can be achieved without this external intervention. Two recent papers, discussed in the blog entry below, highlight the questions at hand.