IF you hadn’t guessed already, I’m busy trying to write a paper at the moment. This being the case, I have managed to successfully postpone this onerous task by spending time reading other people’s papers. I’m now going to spend a little more time explaining one of them you, my lovely readers.
Many years ago, when I was a grad student, I found myself at an otherwise rather dull conference on nucleic acid research; but fortunately it was not a complete wash-out, a chance conversation with a grad student who happened to be presenting a poster on the adjacent board to mine introduced me to the world of molecular mimicry.
So what is mimicry and why is it important in the natural world? Mimicry is the imitation of one species by another, with the most well known purpose being to avoid being eaten. Most people will have encountered hoverflies, and may in the first instance have mistaken them for a wasp or a bee; from an evolutionary perspective, predators such as birds have also learnt to associate these warning (aposematic) colours with a stinging or poisonous prey, and so the Hoverfly gets to fly another day.
Another form of mimicry is where a predator mimics their prey, a wolf in sheep’s clothing; a good example being spiders that mimic the ants on which they prey.
Whilst these are clear examples of mimicry at the scale of the organism, mimicry goes significantly deeper in biology, to the molecular world.
If you happen to be a bacterium, one threat to your continued existence might be infection with a bacteriophage, a virus that infects only bacteria. The bacteriophage will inject its DNA into you, initiating a process wherein it will use your cellular machinery to make more of itself. Invasion is not limited to bacteriophages, it can also come in the form of mobile genetic elements (MGEs) that, as the name suggests, are bits of self-replicating DNA that encode various genes that ensure their own survival and, like the bacteriophage, they also need a cell in which to replicate.
It makes sense for the bacteria to have some defence against this, an immune system of sorts; infection with a bacteriophage can result in cell lysis and death, and MGEs place a metabolic cost on the host cell, making them potentially less fit in the competitive business of life.
In fact, bacteria do have something that is analogous to an immune system, they’re called restriction endonucleases, enzymes whose role it is to cut invading DNA into pieces small enough to be chewed up and rendered useless by the cell. The bacteria’s own DNA escapes being cut up by its own defences because the specific DNA sequences that are attacked by such enzymes have been modified with a chemical that protects that site.
All this is no good for the bacteriophage or MGE, which are now subject to the rather strong selective pressure of ceasing to exist. To counter this problem one particular MGE, a conjugative transposon called Tn916, employs counter-measures; it encodes a highly elongated protein called ArdA that, curiously enough, mimics a 42 base-pair fragment of DNA comparable in length to the target DNA bound by one of the bacteria’s restriction endonucleases. It is the largest DNA mimic yet reported.
By using ArdA as a decoy, Tn916 is able to go about its business. In the current print edition of the journal Nucleic Acids Research, researchers in the lab of David Dryden at the University of Edinburgh report the structure of ArdA and highlight the issues of horizontal gene transfer of MGEs such as Tn916. An important feature of MGEs such as Tn916 is that they also encode antibiotic resistance, and by inserting and then excising themselves from host genomes, they also pick up other useful bits of DNA; their spread amongst common pathogens, such as Enterococcus, in humans is therefore a significant public health risk.
In this figure (and non-biochemists bear with me), (b) is the backbone structure of the ArdA protein molecule (consisting of two ArdA molecules joined together in the middle). In (c) The researchers then highlight the negatively-charged acidic amino acids (in red), which appear to form a helical pattern across the surface. Finally, in (d), the researchers superimpose the phosphate-backbone structure of a DNA double-helix (red & white blobs) with the acidic residues from (b). The acidic amino acids of ArdA match one DNA strand (shown in green), and match the other DNA strand (shown in yellow).
Members of the Dryden lab identified that genes coding for ArdA found in six other pathogens are, to one extent or another, similarly able to overcome the archetypal restriction-defence systems of E. coli.
The sequential acquisition of single-point mutations to code for a predominance of acidic amino acids and DNA mimicry is certain to be a rare event.
So whilst such mimics may be rare, the advantage in possessing such a counter-measure decoy means that they will spread rapidly through their ecological niche; ArdA is widely distributed in bacteria, on MGEs, and other DNA mimics are found in bacteriophages. Ultimately, by making MGEs able to resist the deleterious effects of cellular defences in the form of restriction endonuclease, ArdA is actually favouring the acquisition of new genetic material in bacteria, which can lead to the spread of antibiotic resistance; so potentially good news for bacteria, but bad news for us.
McMahon, S., Roberts, G., Johnson, K., Cooper, L., Liu, H., White, J., Carter, L., Sanghvi, B., Oke, M., Walkinshaw, M., Blakely, G., Naismith, J., & Dryden, D. (2009). Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance Nucleic Acids Research, 37 (15), 4887-4897 DOI: 10.1093/nar/gkp478
UPDATE: Very happy to have been selected by not one, but two editors at ResearchBlogging.org, and receive credit from none other than Dave Munger (Cognitive Daily), who I last saw in Second Life, for the 10th September edition of Seed Magazine.
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7 thoughts on “Mimicry: survival or flattery?…”
That is amazing… Thanks for introducing me to molecular mimicry! Now to get on with my paper I’m procrastinating about.
I have finally acquainted myself with your scientific writing after our chance meeting on the train-do you remember Jim?- and believe me when I say that it is revitalising to read about mimicry at 02:04 on a Saturday morning and now i’m thinking about everything I don’t know about-which I confess-is ample, arduous and confusing as well as impossible.
I’m going to be selfish and pick out the part which really amazed me:
“Invasion is not limited to bacteriophages, it can also come in the form of mobile genetic elements (MGEs) that, as the name suggests, are bits of self-replicating DNA that encode various genes that ensure their own survival and, like the bacteriophage, they also need a cell in which to replicate.”
I think I will now try to sleep.First time I have lulled myself to sleep with the thought of MGEs strenghening defenses…poor weak celluar defence systems, rattly and old and in need of revolution.
Truly enjoyed reading this-
Glad you found the article interesting, even if it represents some of the ‘arduous and confusing as well as impossible’ of which you speak 😉
By the way, it was the Greek Democritus who coined the term atom, which I think you suggested. Not 100% sure he actually did the experiment of mixing water and alcohol though, it may of been his teacher Leucippus, or perhaps earlier scholars.
Hope your new house is living up to expectations.
I like confusing and impossible. We are inseperable companions.
And i’m glad it was Democritus. I knew I liked him a lot for some good reason.
I am going to buy New Scientist later-I may be on here asking you questions.(Yes, that was an advance warning.)