Once upon a time in the RNA World…

Okay, so here is the promised speculation:

If we try to build a logically consistent hypothesis as to the steps between “not life” and “life”, our thinking naturally centres around something very much like RNA. In general inorganic chemicals do not become organic chemicals without an organic catalyst (thus the need for metabolism). So, there has always been a gulf there between the inorganic world and the so called “genetic takeover”. However, it seems that under certain circumstances two of the key components of life, Uracil and Cytosine, can arise from inorganic constituents. So we can hypothesis a form of proto-RNA.

However, these molecules would be very unstable and need to be kept in a particular aqueous medium. Thus we hypothesise the proto-cell. And more than just hypothesise, we can build such things in the lab out of simple fatty-acids. This proto-cell would have to be mostly permeable (as opposed to our modern semi-permeable membranes), since the absence of proteins precludes a complex membrane transport system and otherwise the proto-cell would lack the nutrients to thrive.

All of these things are nicely laid out in the review “The Origin of Life on Earth” by Ricardo & Szostak, 2009. However, there is one thing they notably do not cover. Let us imagine this environment proto-cells floating around in a soup of proto-RNA and various proto-metabolites drifting in and out through their fatty acid membranes. But here is the thing. If genetic material can freely diffuse through these membranes (and it can, since there is no way to stop it without stopping everything else) then how does any kind of proto-genome selected for and developed? If the genetic material of any cell is constantly being polluted by foreign material, nothing is going to happen, we are never going to get past this proto-stage. Indeed this infection of foreign material seems a great deal like our modern problem with viruses. So what is a cell to do? Exactly what single celled organisms do against viruses today.

See, bacteria generate a basic self/other dichotomy and protective response based on enzymes known as restriction/modification enzymes. This can be seen as the simple most instance of our much more complex immune systems that work through much different mechanisms but stem from a similar system of self/other recognition at a molecular level. Restriction enzymes cut DNA at specific point. Modification enzymes tag DNA to indicate that it should not be cut. When the system is working properly, all the DNA in a given cell is tagged. So any foreign DNA that enters is untagged, therefore not self, therefore cleaved to pieces by the restriction enzymes. It is conceivable that this system has its first roots in an RNA world where a membrane line defence against foreign genetic material was impossible, leaving the proto-cell to rely on a catalytic defence.

However, we must remember that this is an RNA world we are talking about. No DNA. No proteins. So, does that mean no enzymes? Well…you might think so. One of the things that tends to get glossed over in modern bio is the wonder of the ribozyme. Ribozymes are catalytic RNA. RNA that serves the same function as an enzyme (a brilliant example of RNA with catalytic activity is the ribosome, which is ~70% RNA including all of its catalytic sites). And ribozymes that function like restriction enzymes are extant today.

Now, it may never be possible to know what actually occurred at the dawn of life, but trying to produce logically consistent hypotheses is entertaining, and I think these putative proto-ribozymes fill a gap in the current theory and explain how the proto-genome could have the protection it needed to grow towards something resembling our modern day biology.

Hah, made it before midnight!