Welcome to TheDesignMatrix.com

Find out more about the upcoming new book The Design Matrix: A Consilience of Clues and author Mike Gene. Check below for the blog by the author!

The Unfolding of RecA

August 22nd, 2007 by Mike Gene

In my previous essay, I offered some support for viewing RecA as an evolution gene: it is ubiquitous, ancient, and plays a key role in the important and evolutionarily significant process of recombination. Also, the endosymbionts suggest that it can act like a switch when it comes to genomic integrity over time.

I’ve raised this all as an alternative perspective, where “RecA’s functions are more fully realized across generations, something we would expect from an evolution gene.” In other words, it’s a question of observational scale. If, for some reason, we were restricted to making observations on the scale of milliseconds, we might be under the impression that RecA’s function is to bind ATP, because the DNA repair functions of RecA are dependent on more time and other machinery. Thus, I’m raising a perspective that expands time even further, noting that DNA repair and recombination (what we measure in the lab) is part of the evolution-function of the gene (how an observer with a larger time frame might see it).

In my last essay, I mentioned that RecA was universal among free-living bacteria and that its amino acid sequence was strongly conserved. It’s now time to consider another aspect.

RecA exists as a single copy gene in most eubacteria. There are some exceptions where eubacteria have two copies, such as in Myxococcus xanthus, but since these cases are typically restricted to specific species, it is likely that these few exceptions represent recent gene duplications.

That most bacteria have only one copy of the RecA gene is actually quite interesting, as it means that billions upon billions of years of gene duplication have failed to expand RecA into a family of RecA proteins among bacteria. In essence, there is some kind of resistance to expansion by gene duplication. This does not mean gene duplication itself has failed to occur, as I’m sure this gene has been duplicated countless times throughout microbial evolution. But it would seem that when this occurs, it is almost always the case that the duplicate either decays away or is selected against. What’s more, this pattern is consistent with the last common ancestor of all bacteria also possessing this “resistance to expansion by gene duplication” as far as RecA is concerned, as the genome of this last common ancestor apparently had only one copy. Thus, whatever the cellular or genomic reasons for preventing RecA from blossoming into a family of RecA proteins, it has effectively defined eubacteria from the start and then billions of years afterward.

When we turn to Archaea, even though their cellular and genomic complexity is not really that different from eubacteria, it looks as if the constraint has been partially lifted. Many distantly related species have two versions of RecA, known as RadA and RadB. Although some species have lost RadB, the twin versions are distributed widely enough to indicate that the last common ancestor of Archaea possessed these two copies. The RadA and RadB proteins are also somewhat different from the RecA protein, in that they lack a C-terminal domain that is present in RecA. In addition, the RadA protein also has a N-terminal domain that is missing in RecA. Whether or not these changes helped to partially lift the constraint off expansion by gene duplication, we’re still left with no more than two copies throughout the billions of years archaea have evolved.

When we turn to Eukarya, the picture changes dramatically. Eukarya possess a RecA version that is more similar to the archaeal protein. But when we survey vertebrates and flowering plants, we find seven different versions: Rad51, Rad51B, Rad51C, Rad51D, DMC1, XRCC2, and XRCC3. These different versions carry out various specialized, but related, roles in DNA repair and recombination. What’s more, by surveying many eukaryotic genomes, these seven versions were present before the split of animals, plants, and fungi. In other words, they likely existed in a unicellular, eukaryotic state.

Thus it would appear the eukaryotic genome quickly escaped this constraint and that very early in eukaryotic evolution, both the RadA and RadB versions underwent successive rounds of gene duplication that were quickly followed by subfunctionalization. This appears to then have set the stage for the further evolution of more complex interactions that are associated with multi-cellular life. In other words, a distinct teleological perspective emerges, one where RecA had sat there for hundreds of millions of years carrying out its role in a simple genome and then when it found itself in some ancient eukaryotic context, very early on, it unfolded into several different specialized versions that would then go on to further facilitate the evolution of multi-cellular life. How lucky.

And that brings us to one of the versions known as DMC1. But we’ll save that for the next installment.

Posted in General |

One Response

  1. Let There Be Sex | The Design Matrix Says:

    […] Previously, we have seen that the eukaryotic versions of RecA (Rad51, Rad51B, Rad51C, Rad51D, DMC1, XRCC2, or XRCC3) were spawned when the domain Eukarya probably existed in a unicellular state. We’ve also seen that removal of Rad51 from the mouse genome was lethal. The same holds true for Rad51B, Rad51C, Rad51D, and XRCC2 (such knock-out experiments with XRCC3 have apparently not been done yet). But removal of DMC1 is not lethal. In fact, the phenotype for such a knock-out mouse is as follows: Homozygotes for targeted mutations are sterile with failure of homologous pairing in meiotic prophase in males and disrupted oogenesis in embryonic females with absence of germ cells in the adult ovary. […]

Leave a Comment

Please note: Comment moderation is enabled and may delay your comment. There is no need to resubmit your comment.