Last week researchers from Thomas Jefferson University published a paper that suggested that Polymerase Theta can use RNA to change DNA.
What does this mean? Why is this interesting?
Do you know how DNA works? Do you understand natural selection and evolution?
I thought I did. But this just adds a whole new layer of complexity. I’ll start from the beginning.
Put simply, DNA is a double helix made up of strings of four ‘letters’. The strings unravel and the letters code for RNA which then codes for the creation of a protein which acts as a building block, or as an enzyme which is a chemical catalyst that encourages something else to happen. DNA is the recipe that makes us. In a software analogy, I think of DNA as a library of code. Intriguingly, just like in old software, there’s loads of DNA that just sits around redundant without any apparent purpose.
Sex & selection
In organisms that have sex, half of the DNA goes into each sperm or egg. In the process of getting the DNA in to the sperm or egg mistakes can happen, altering the code. These are called mutations. When the sperm and egg combine, the two halves from the two parents combine.
Bits of DNA that code for proteins or enzymes that cause organisms to live longer, or have more offspring, are likely to become more common. So if mutations are beneficial they can spread and change happens. This is natural selection.
Over a very very very very long time, over many many many many generations the action of natural selection causes evolution: species change over time and new species might form.
Something as complex as an octopus has evolved from a single-celled organism.
Incidentally this has always been a leap of faith for me. Despite the huge expanse of geological time, it still seems to me to be an act of faith to believe an eye can evolve simply by the incremental selective benefits of a series of the kinds of tiny changes resulting from the accidental alteration of a code for a protein. Think how many steps you have to go from just a single to sell, to something with rods and cones, a lens, and a pupil. Now I’m no creationsit, but I don’t think this leap of faith is acknowledged enough, especially by those who deify science.
There is a question about the level at which natural selection works. Does it work on genes, organisms, or groups / populations?
When I studied this in the 90s, it was thought to act at the gene level (as summed up by Richard Dawkins in The Selfish Gene). In other words, a successful gene could spread if it replicated itself succesfully, even if in the long run it was ‘bad’ for an organism or a population — the organism became just a vehicle for a set of genes.
The idea of group selection or ‘for the good of the species’, was considered anathema. The reason being there was no natural selection at group level, so there was no mechanism to explain how group selection could occur. For example, a gene that caused self-sacrifice for the benefit of others would quickly die out because it would keep sacrificing itself. The species isn’t a thing with its own desires and direction. Competition between genes and between individuals was emphasised, and anything that superficially looked like group selection (e.g., attenuation of virulence in viruses) was ultimately explained by gene selection, although sometimes after desperate contortions.
Also anathema was Lamarckianism. This is the nineteenth century idea that a blacksmith’s son will have more muscular arms because of the work of his parents, and that giraffes evolve long necks because for generations they stretched to reach the top branches. In other words, the characteristics acquired or lost through life are inherited. (Lamarck was also afflicted by the teleology of the age and thought there was some kind of inherent drive to increased complexity and improvement).
Over the last 25 years the simplified sketch I’ve drawn has become more complicated. We now also have to consider epigenetics.
Put simply, epigenetics is the process by which different bits of DNA are turned ‘on’ or ‘off’. Processes include methylation and histone modification. It seems that these changes can be inherited.
The classic example in humans is the Dutch ‘hunger winter’ of 1944–45. Offspring born during the famine were smaller than those born the year before, and in later life they had increased risk of glucose intolerance and increased chance of metabolic and cardiovascular disease. This could have just be considered to be the effects of deprivation in early life. However these risks were inherited by their children who lived in a time of plenty. Something was altering how their DNA was expressed. In other words, the lived experience of grandparents affected the health of their grandchildren. In the software analogy I think of epigenetics as a user programme that selects which bit of the code library to use.
While DNA is inherited and is acted upon by natural selection, we now understand there is a metamachinery which affects how DNA is used, which is also inherited to some extent. As such, if it affects reproductive success, it must also be presumed to be subject to natural selection.
Our developing knowledge of epigenetics indicates that our experience in life is even more shaped by that of our ancestors than we already thought. Not only do we have the burden / boon of our DNA, our culture, the parenting we receive, the developmental environment in the womb, the environment we grew up in, our health, our nutrition, our biome, our luck; we also have the burden / boon of our ancestors’ experience. Collectively I refer to this as Ananke. This raises questions about free will and responsiblity, which filter through into ethics and jurisprudence.
Bringing it back to the Thomas Jefferson Univerity paper, we had thought that the process by which RNA took the code from DNA to make proteins was one way only. The news that RNA might be able work the other way too, to write to DNA, seems really important.
The paper’s lead author, Dr. Pomerantz, says “In healthy cells, the purpose of this molecule may be toward RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to further understand how polymerase theta’s activity on RNA contributes to DNA repair and cancer-cell proliferation”.
Sensibly they’re excited by specific applications.
Return of Lemarck (there it is)
I’m less senbible. I know this is only one specific process that’s been identified, and it’s not a generalised phenomenon. I know it’s early days, and my understanding of epigenetics is thin. I know a little knowledge is a dangerous thing. But it seems to me this discovery further opens the door to a different understanding of evolution.
The user programme now not only chooses which bits of the code library to use, it can change the code library itself. Not only can the epigenetic metamachinery be inherited, it can also alter the DNA.
This means that, potentially, we’re not just waiting for natural selection to blindly and slowly work on a new chance mutation in DNA. Instead this discovery implies that DNA can be changed directly, perhaps by some kind of response to the environment. If this is the case, evolution can work more quickly and reactively.
My questions are what is controlling polymerase theta, and what determines how it alters DNA?
There is the chance that whatever it is that’s in control, let’s call it life, can influence evolution by rewriting DNA. For the first time we have a tiny insight into a mechanism by which this could work. This reintroduces the idea of direction, goal, or telos, in evolution; the idea of a hand on the rudder, which also implies a desired destination. This also permits group selection in a way that would not have been possible before.
While I still don’t believe there to be anything steering the rudder, suddenly what had been completely discredited ideas are much harder to dismiss out of hand.
And now I will really take a leap. I’m quite partial to Jungian psychology. His model of consciousness and individuation makes far more sense to me than Freud or Adler. However his idea of the collective unconscious (and synchronicity for that matter), always seemed like so much mumbo jumbo.
For Jung, the collective unconscious is a set of shared archetypes and symbols that persist externally to the individual but are nonetheless influential internally. For example, the symbol of a snake might have meaning in itself, rather than just to the individual, and this meaning is universal even as it is interpreted in infinite ways by infinite individuals. I’ve always thought of the Zeitgeist as being a manifestion of the collective unconscious. Both the Zeitgeist and collective unconscious are somehow observable, but impossible to pin down, analyse, observe, or touch, and both are as likely to be apophenia eas anything else. There’s no evidence for them, nor any real theory of how they might work.
However, the discovery that RNA might ‘write’ to DNA suddenly opens up the chance that, somehow, experiences can directly alter genetics; that the user programme can alter the code libraries, that memories or knowledge, can somehow be encoded for future generations. And, once encoded in DNA, they can be passed on in ways that are different to culture. Or to put it another way, culture could become genetic. Perhaps this is what some of the unused DNA is actually doing? Perhaps it stores something that Jung has called the collective unconscious?
This is all highly speculative, and is a massive extrapolation from a single discovery. Calling it pseudo science would give it too much credence. But I am fascinated and challenged by the miniscule chance that telos might be reintroduced into evolution, that we have the inkling of a mechanism for the collective unconscious, and the inkling of a process that might help explain biological complexity without having to rely on incremental natural selection of tiny changes over geologic time.