Annihilation and the Reality of Genetic Mutations
Earlier this year, the film Annihilation came out relatively under the radar, but generally well-liked to those who saw it.
It’s an original, and surprisingly good sci-fi film based on a novel of the same name, where a group of military scientists enters a quarantined zone along the gulf coast where the presence of an alien meteorite has created a land of mutated creatures and animals.
It’s visually stunning and impeccably acted, but unfortunately, the science can get decidedly hand-wavy.
It does it’s best to give a vague explanation for why the biology doesn’t make sense (the alien “shimmer” is acting like a lens, refracting everything within back on itself, including genes), but these explanations frankly fall a little short.
The main thing Annihilation (and many other films) gets wrong about genetic mutations are their effects.
DNA is the building blocks of life, and yes, a single-base mutation can have a large effect, but in many cases, evolutionary- or even any sort of noticeable- change is based on the accumulation of many mutations with small effects.
What’s more, most mutations are actually totally neutral, depending on their context or location.
This is simply because there is a lot of redundant regions and non-coding space in our DNA, so only a relatively small number of bases would actually have an effect if mutated.
Of those that do, most non-neutral mutations are deleterious (IE an entire nucleotide is removed) because they can effect the way the entire gene after that base is read and translated.
In general, the more base pairs that are affected by a mutation, the larger the effect of the mutation, and the larger the mutation's probability of being noticeable.
To better understand the impact of mutations, researchers have started to estimate distributions of mutational effects (DMEs) that quantify how many mutations occur with what effect on a given property of a biological system.
In evolutionary studies, the property of interest is fitness, but in molecular systems biology, other emerging properties might also be of interest.
It is extraordinarily difficult to obtain reliable information about DMEs, because the corresponding effects span many orders of magnitude, from lethal to neutral to advantageous; in addition, many confounding factors usually complicate these analyses.
To make things even more difficult, many mutations also interact with each other to alter their effects; this phenomenon is referred to as epistasis.
However, despite all these uncertainties, recent work has repeatedly indicated that the overwhelming majority of mutations have very small effects.
Of course, much more work is needed in order to obtain more detailed information about DMEs, which are a fundamental property that governs the evolution of every biological system.
What are genetic mutations really?
At the most basic level, mutations are simply changes in the genetic sequence, and they are a main cause of diversity among organisms. These changes can occur at many different levels, and they can have widely differing consequences.
In biological systems that are capable of reproduction, we must first focus on whether they are heritable; specifically, some mutations affect only the individual that carries them, while others affect all of the carrier organism's offspring, and further descendants.
For mutations to affect an organism's descendants, they must: 1) occur in cells that produce the next generation, and 2) affect the hereditary material. Ultimately, the interplay between inherited mutations and environmental pressures generates diversity among species.
Although various types of molecular changes exist, the word "mutation" typically refers to a change that affects the nucleic acids. In cellular organisms, these nucleic acids are the building blocks of DNA, and in viruses they are the building blocks of either DNA or RNA.
One way to think of DNA and RNA is that they are substances that carry the long-term memory of the information required for an organism's reproduction. This article focuses on mutations in DNA, although we should keep in mind that RNA is subject to essentially the same mutation forces.
If mutations occur in non-germline cells, then these changes can be categorized as somatic mutations. The word somatic comes from the Greek word soma which means "body", and somatic mutations only affect the present organism's body.
From an evolutionary perspective, somatic mutations are uninteresting, unless they occur systematically and change some fundamental property of an individual--such as the capacity for survival.
For example, cancer is a potent somatic mutation that will affect a single organism's survival. As a different focus, evolutionary theory is mostly interested in DNA changes in the cells that produce the next generation.
In Annihilation, while the mutations the characters and environment experience are decidedly more visually interesting than real mutations would be, there is at least some effort to depict the mutations as random, which is a hallmark of mutation theory.
The statement that mutations are random is both profoundly true and profoundly untrue at the same time.
The true aspect of this statement stems from the fact that, to the best of our knowledge, the consequences of a mutation have no influence whatsoever on the probability that this mutation will or will not occur.
In other words, mutations occur randomly with respect to whether their effects are useful. Thus, beneficial DNA changes do not happen more often simply because an organism could benefit from them.
Moreover, even if an organism has acquired a beneficial mutation during its lifetime, the corresponding information will not flow back into the DNA in the organism's germline. This is a fundamental insight that Jean-Baptiste Lamarck got wrong and Charles Darwin got right.
However, the idea that mutations are random can be regarded as untrue if one considers the fact that not all types of mutations occur with equal probability.
Rather, some occur more frequently than others because they are favored by low-level biochemical reactions. These reactions are also the main reason why mutations are an inescapable property of any system that is capable of reproduction in the real world.
Mutation rates are usually very low, and biological systems go to extraordinary lengths to keep them as low as possible, mostly because many mutational effects are harmful.
Nonetheless, mutation rates never reach zero, even despite both low-level protective mechanisms, like DNA repair or proofreading during DNA replication, and high-level mechanisms, like melanin deposition in skin cells to reduce radiation damage.
Beyond a certain point, avoiding mutation simply becomes too costly to cells. Thus, the mutation will always be present as a powerful force in evolution.
What the future might bring
While mutations may often be detrimental to living organisms, they are incredibly useful in the laboratory.
For instance, using a technique known as homologous recombination, scientists have systematically knocked out every gene in the entire yeast genome, creating a yeast deletion library of ~5000 single gene deletion mutants.
Since then many more library collections have become available. Some of them add epitope-tags to host genes, while others are made in other organisms.
With the help of high-precision robotics, the availability of deletion libraries has permitted scientists to perform high-throughput screening assays to probe for drug targets, to identify genetic interactions on a genome-wide level, and to study the complexity of genetic networks.
There are dozens of similar assays and procedures being used in scientific laboratories every day to develop drugs, cure diseases, and further our understanding of science in general.
And more uses for genetic mutations are being developed all the time. Who knows what advances the future will bring.
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