If we view evolution as a function, it stands to reason that life would be endowed with a tool kit of evolution genes. Such genes would interface with life’s architecture to facilitate evolution. That is, while evolution is inevitable in a population of imperfectly replicating cells, the evolution genes would function to effectively catalyze evolution.

But what part of life’s architecture might be targeted by these evolution genes? An obvious candidate is the DNA itself, as it is the DNA that codes for the machinery of life. For example, when it comes to the evolution of body plans, evo-devo teaches us that changing the pattern of switches in front of a gene is an integral part of such evolution. The switch sets, in turn, are altered over time through the process of genetic recombination. Recombination can remove switches, add switches, or swap different versions of a switch in or out. Afterwards, natural selection behaves merely as the editor to weigh whether or not such alterations are acceptable.

The process of recombination has long been known to be very important in generating variation for evolution. As one scientist notes, “The general feeling would probably be that in some undefined way recombination allows organisms to more effectively evolve to adapt to changing environmental conditions.”

So, as our first candidate for an evolution gene, meet RecA.

RecA is a protein that is ubiquitous among bacteria. At first glance, there doesn’t seem to be anything special about it. It’s a typically sized protein of around 350 amino acids and it carries out three very basic functions: it binds to DNA, it binds to other proteins, and it binds to ATP. So why consider this a candidate for an evolution gene?

When I mentioned that genetic recombination is a powerful evolutionary force, it’s sometimes easy to forget that recombination is not an abstract process that happens all by itself. It is a process that happens because various proteins interact with the DNA to recombine it. And in this regard, RecA is the star. RecA has the ability to bind to a single strand of DNA (generated by abiotic or biotic forces) and hold on to it as it simultaneously scans another region of the double-stranded DNA in search for nucleotide sequences that are complementary. This is a process known as homology search. Once a complementary region is found, RecA then promotes the actual process of recombination known as strand-exchange (or crossing-over).

But it gets better. In addition to being the core protein responsible for recombination, RecA also interacts with another protein, LexA, to initiate the SOS response in bacteria. In fact, this process itself suggests that the ability to generate variation for evolution is built into the fabric of life, as I previously explained.

Since RecA facilitates the retooling of the DNA molecule, it is a good candidate for an evolution gene. Yet another reason for thinking it is a good candidate is its ubiquitous distribution across all life. Not only is a widely spread (and conserved) among all bacteria, but RecA versions are found in life’s other two major domains: Rad51 in eukarya and RadA in archaea. These proteins carry out the same basic functions. For example, while the process of recombination during the formation of gametes (meiosis) is more complex in eukaryotes, Rad51 carries out the core process. That “RecA” is so widely distributed suggests it could have been present in the first cells and has been facilitating evolution ever since.

RecA is truly a remarkable protein. Even though it is only about 350 amino acids in length, it carries out the multiple functions of binding multiple DNA strands, coordinating their exchange, binding ATP and hydrolyzing it, and interacting with other proteins. In fact, according to one review [1], the functional domains responsible for these activities closely map together and may even overlap. How is all this carried out?

I’ve left out one very important part of the story – RecA is not functional as a monomer, it only becomes functional when it forms protein fibers that wrap around the DNA.

In other words, recombination occurs because tubulin-like proteins stretch the DNA by forming a dynamically lengthening tube around it. In this way, the growing protein tube can hold onto the single stranded DNA with one “hand” while using its other “hands” to unravel double stranded DNA such that the single-stranded DNA can be used to probe the unraveled DNA for regions that are complementary.

You might have noticed I said “tubulin-like.” Is this simply because RecA forms a semi-hollow protein tube? No. There are several other features that have led one reviewer, for example, to note:

The dynamic behavior protein under conditions of ATP hydrolysis is thus conceptually similar to that of other NTP-hydrolyzing, self-assembling proteins, such as actin and tubulin. [2]

Like tubulin, RecA formation starts slowing with a nucleation step, where a small number of monomers must form a seed that can then be extended. Once formed, like tubulin, RecA then grows at one end by the incorporation of RecA monomers bound to ATP (tubulin dimers add to one end and must be bound to GTP). Like tubulin, the NTP hydrolysis is not needed for assembly, but instead is needed for disassembly. This means that RecA, like tubulin, assembles at one end and disassembles at the other end, forming something like a treadmill. According to one team of researchers:

We argue that RecA can “proofread” the ssDNA by its own binding fluctuations. These fluctuations are similar to microtubule dynamic instability. The assembly dynamics constitute a kinetic proofreading cascade that is a “hair-trigger” sensor of DNA length. Enhancing biomolecular precision by fluctuations, which may seem somewhat counter-intuitive in a deterministic world, is presented as a natural design principle in the noisy realm of the living cell. [3]

A microtubule-like structure is thus in charge of genetic recombination.
Finally, if RecA is an evolution gene, this would lead to an obvious prediction - removal of RecA should compromise an organism’s ability to evolve. We’ll consider this prediction in the next installment.