Is Competence a candidate system to study quantum biology?

My time in the Redfield lab is coming to an end. I’ve been thinking about a paper on a peculiar discovery about DNA  for the last couple of weeks, and how it might be important for the field I was in. Before I get into the actual paper I’ll discuss what quantum biology is. This post is very exploratory, I was trying to learn all this as I go through the literature. The technical concepts go far beyond my layman understanding and there are many, many highly fringe ideas(including Nobel prize winners publishing terrible papers about DNA teleportation). It was my hope that as I was doing the research for this post some coherent idea or structure would form, sometype of “aha!” moment would come if I looked hard enough but nothing came together. I did learn a lot and I’m glad that I did a fairly comprehensive search on the idea, however in retrospect this topic was much to broad and speculative to have attempted. Perhaps in a year or two it would be fruitful to look again as the science matures. I found very little solid evidence of quantum effects in DNA, got confused often and conclude that most of the ideas of extra quantum information being stored in DNA and even concepts I thought were quite reasonable like DNA electrical conductance recruiting repair proteins to be largely unfounded. I did come up with an experimental idea, however it isn’t great and likely is not worth pursuing.

Quantum Biology

Several biological process have been recently been found to exploit quantum effects beyond basic chemistry. These biological process go far beyond the inherent  and ‘trivial’ quantum nature of chemicals that allow for essential properties such as the conversion of chemical energy. These are the large scale manipulations of spooky effects to gain new abilities and functions.

The classic example of quantum biology is hydrogen tunelling. The proton coupled electron transport reaction catalyzed by soybean lipoxygenase  transfers hydrogen from one molecule to anouther – without ever having to get overcome the energy barrier needed (ref 1). The movement of hydrogen can not be explained by classical physics as the proton appears to bypass the path ti would need to take. Olfaction likewise is hypothesized to be conducted by electron tunneling.

The quantum effects I’m going to focus on in depth for the following two paragraphs are entanglement in magnetoception and coherence in photosynthesis. Entanglement is when two objects share the same existence and fate despite being in two entirely separate places. Coherence is the famous one from Young’s double slit experiment, the ability of an object to be both a wave and a point particle at the same time allowing travel through all possible routes until the wave function collapses, and maybe the single most alien thing to the way we are accustomed to things working. Coherence is comprehensible to understand, but it frustrates the brain in a funny way to think about what is actually happening.

Migratory birds have long been to known to have the ability to sense magnetic fields. Early theories to explain this ability were that birds have magnetite crystals in their heads that they use as a compass. Birds do have magnetite crystals in their heads, and other organisms such as magnetotactic bacteria do use magnetite to sense magnetic fields so it was natural to assume this was the true mechanism. However two arguments have been made against this theory. Humans also have magnetite and don’t sense magnetic fields, and more importantly migratory birds ability to sense magnetic fields is completely light dependent. In the dark they lose their magnetoception. The prevailing theory is that a light sensing molecule in the photorecptor cells of these animals called a cryptochrome is responsible. When blue light hits the cryptochrome it  produces two radicals(chemicals that have single unpaired electrons) whose electrons are entangled – sharing the same existence. The crypotochrome enters a signalling state that can only be reverted if the entangled electron spins are in one particular configuration(anti-parallel). External magnetic fields can effect the probability of the entangled pair being  anti-parallel, therefor biasing how long a cryptochrome is in a signalling state, and in this way birds have a physiological sensor of magnetic fields. A great resource for information on bird magnetoception here. Magnetoception has been seen in many other diverse organisms such as fruit flies and Arabidopsis. Unfortunately, not in humans

The second ability I investigated was photosynthesis, which is a marvelous process – converting radiation of a specific into usable chemical energy and doing so well at an incredible rate of speed and with enough efficiency to make solar panel researchers envious. I like how Philip Ball put the process in his recent article, “Photons hitting an antenna molecule will kick up ripples of energized electrons — excitons — like a rock splashing water from a puddle  and move through reaction centers to deliver charge”. These excitons are coherent, the electron travels as wave through multiple paths, finds the shortest route possible and then instantaneously appears in a reaction center. Only four years ago the coherence hypothesis was confirmed, albeit at cryogenic temperatures, and in 2010 it was shown at room temperature. Computer simulations have addressed the long standing question of how coherence can last such a long time in a cellular environment, showing that environmental noise can substantial increase coherence(2)

DNA

So that’s some of the cool stuff coming out of quantum biology. It’s interesting but not very relevant. It’s also incredibly unfamiliar territory for biologists. Now for why I’m interested in it, is there anything quantum about DNA?

I struggled heavily with this literature,  trying to find what quantum effects may be present in DNA. Unlike the previous sections, there are no seminal papers, and almost every good paper approaches it from a heavy physics perspective rather than a biology perspective. What I can find is mostly in obscure journals and the theory and methods are alien to me. One of more substantial things I found was that DNA may have a quantum quirk called “Phonons”(5). Phonons aren’t particles themselves, but describe the collective excitement of electron clounds oscillating uniformly at the same frequency. A recent paper makes the claim that phonons make a large contribution to DNA structure, saying that there is missing energy required to keep a double helix together(6). I do not know what to make of this paper, it provides no evidence for it’s claims and a lot of cmments about it are skeptical, I really can’t tell. The interesting implication with phonons is that they can be informational, a base mismatch could alter the signal and be detect far along the strand. While I was studying this I also read papers the electrical conductiveness of DNA, which also has the potential to be informational as the resistance and nature of conductance can change, for instance studies have shown mismatches and abasic strands have reduced conductivity(4).

Now for the paper that inspired this investigation, “Spin Selectivity in Electron Transmission Through Self-Assembled Monolayers of Double-Stranded DNA”. The authors put down a layer of 4 different sized dsDNA sequences(26bp to 76bp long) on a bare gold substrate at room temperature. Linear polarized laser radiation hit excited electrons and caused them to be ejected from gold plate. Electrons that have spin antiparralell to their velocity were preferentially transmitted through the chiral structure of DNA and detected by a mott polarimeter. With the 76bp DNA 4 out of every 5 electrons that filtered through the DNA were antiparralel. Electrons that were not transmitted are captured by the DNA and eventually tunneled back to the grounded gold substrate. DNA is a chiral molcule, both in sequence and in double helix structure so it naturally generates a magnetic field when a charge passes through it however the authors point out that this effect isn’t thought to be enough to cause such specificity.  When the samples where damaged by UV radiation spin specificity was lost.

What is the significance of this finding? Potentially nothing. The effect is large and suprising, but so was the spin filtering effect of graphene and that doesn’t mean anything. And just because DNA has this property when aligned tightly in a physics lab doesn’t mean it has it in vivo. What initially intrigued me about this effect is that this technology, spintronics is used for data storage. Computer hardrives and solid state devices use electron spin selectivity as a way to store information. Electron spin specificity can be informational, and is also a property of lifes information storage system? Seemed like something worthwhile to investigate. However there is currently no evidence that electron spin is biologically important to DNA’s function, and this result was so surprising I don’t think anyone predicted it.

How do proteins find their DNA targets?

One of the reasons I started thinking about this is because proteins find their DNA targets exceptionally well(3). How DNA binding proteins find their cognate target sequence, and how DNA repair proteins effectively search the genome for mismatches and bad bases is intensively studied and new methods such as quantum dots allow the visualization of individual proteins, however the exact mechanisms are often still not well understood. A 2010 paper beautifully describes nucleotide excision repair proteins in E.coli scanning, hopping, and pausing along DNA to effecitively search for DNA damage. But what causes them to act in disparate ways, what made them pause? Are there local DNA signals that inform proteins where their targets are? In other words, are proteins as perceptive in DNA environments as sharks are in bloodied water?

One paper described double stranded breaks induced by heavy ion induced radiation having repair proteins recruited to them within seconds despite the breaks only being a few bp(7)! However I’ve also found some very thorough papers describing how DNA repair proteins can find their sites without invoking any type of sensing, just sliding around short distances and hopping(8). Several papers argue that repair proteins can sense disturbance in the electric field caused by double stranded breaks to help them find problem regions(a), or that DNA can mediate long range signalling of redox states by electron transport(b).  The theory that long range charge transport is well characterized, being capable of moving very quickly and over long distances(e), however the exact function is still unclear(f)

How can any of this be related to competence?

Under conditions of nutrient starvation the bacteria the lab studies become competent. A while back Rosie brought up about an interesting point about competent DNA, it’s structurally different than normal DNA. Competent DNA  has single stranded gaps and tails. Since then I’ve liked to  imagined that as cells become more and more nutrient starved their genome becomes pocked with little nucleotide gaps[hmm… now that I think about it I never considered how these gaps would distributed. I always imagined the gaps were fairly evenly distributed across the genome, but maybe they are clustered ?], and transformation with uptaken homologous DNA replaces the old junky DNA with a healthier strand. This is the DNA repair hypothesis of competence. The important thing here is that competence structurally changes DNA. So it stands to reason that if there are long range signals of DNA damage, and if under conditions where these signals are no longer clear could affect the induction of competence(unlikely) or the transformation frequency of genomic regions(maybe?).  Static electric fields are one possibility.

Weak static electric fields have been shown to have no significant effect on prokarayotic or eukaroytic cells. Static electric fields in combination with ionizing radiation cause cell death(c). The proposed mechanism is that DNA repair proteins detect electromagnetic disturbances when double strand breaks occur and are activated and recruited, but when the cells are subjected  to an exogenous electric fields they are unable to align properly(d). Maybe log phase bacteria transferred to starvation media will not be as transformable when exposed to a static electric field. I would expect uptake to not be affected, but if there is some type of electrical signaling that is lost maybe transformation and CFUs would decrease. I don’t think there’s enough evidence to justify an exploration of this idea, especially since it would be difficult to control and even if there was an effect it would likely be hard to prove the mechanism.

One thing to keep in mind is that GC rich areas are more conductive than AT regions. Many bacterial genomes, especially their coding regions, are GC rich leading to speculation this is to increase molecular signaling and repair mechanisms. Interestingly Haemophilus influenzae, the labs model organism is  AT rich.

Maybe I could come up with some type of way to test phonons or electron spin(magnetic field?) but neither seem to have any potential, and I need to move on to other things

references:

1) http://www.chem.uiowa.edu/faculty/kohen/group/Journal/C&B99K&K.pdf

2) http://jcp.aip.org/resource/1/jcpsa6/v129/i17/p174106_s1
3) http://www.nature.com/nsmb/journal/v15/n8/full/nsmb.1441.html
4) http://pubs.acs.org/doi/abs/10.1021/jp100264v
5) http://pre.aps.org/pdf/PRE/v76/i3/e031917
6) http://arxiv.org/PS_cache/arxiv/pdf/1006/1006.4053v2.pdf
7) http://www.ncbi.nlm.nih.gov/pubmed/15913400
a) http://informahealthcare.com/doi/full/10.1080/09553000902781121
b) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902267/#R5
d) http://www.sciencedirect.com/science/article/pii/S1568786410000054#fig1
e) http://www.scopus.com/record/display.url?eid=2-s2.0-0033079847&origin=inward&txGid=LawXniJQNRxLYzdJBHFlz5A%3a2
f) http://www.sciencedirect.com/science/article/pii/S0027510799001955
c) http://www.sciencedirect.com/science?_ob=RedirectURL&_method=outwardLink&_partnerName=3&_origin=article&_zone=art_page&_targetURL=http%3A%2F%2Fdx.doi.org%2F10.1080%252F09553000902781121&_acct=C000050484&_version=1&_userid=1022551&md5=63aa0263135ec0f07ffda445bab5f909
8) http://www.ncbi.nlm.nih.gov/pubmed/19290859
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