It shouldn’t come as a surprise to anyone with a basic understanding of evolution that it is a temporal (and also spatial concept). Time is a fundamental aspect of the process of evolution by natural selection, and without it evolution wouldn’t exist. But time is also a fickle thing, and although it remains constant (let’s not delve into that issue here) not all things experience it in the same way.
For anyone who has had to study geography at some point in their education, you’d likely be familiar with the idea of river courses drawn on a map. They’re so important, in fact, that they are often the delimiting factor in the edges of countries, states or other political units. Water is a fundamental requirement of all forms of life and the riverways that scatter the globe underpin the maintenance, structure and accumulation of a large swathe of biodiversity.
Earlier in the year, I had made a comment that, as part of the natural evolution of this blog, I would try to change up the writing format every now and then to something a little more personal, emotional and potentially derivative from science. I must confess that this is one of those weeks, as it’s been an emotional rollercoaster for me. So, sorry in advance for the potentially self-oriented, reflective nature of this piece.
Contrastingly, sometimes we might also use genetic information to do the exact opposite. While so many species on Earth are at risk (or have already passed over the precipice) of extinction, some have gone rogue with our intervention. These are, of course, invasive species; pests that have been introduced into new environments and, by their prolific nature, start to throw out the balance of the ecosystem. Australians will be familiar with no shortage of relevant invasive species; the most notable of which is the cane toad, Rhinella marina. However, there are a plethora of invasive species which range from notably prolific (such as the cane toad) to the seemingly mundane (such as the blackbird): so how can we possibly deal with the number and propensity of pests?
Tools for invasive species management
There are a number of tools at our disposal for dealing with invasive species. These range from chemical controls (like pesticides), to biological controls and more recently to targeted genetic methods. Let’s take a quick foray into some of these different methods and their applications to pest control.
The potential secondary impact of biological controls, and the degree of unpredictability in how they will respond to a new environment (and how native species will also respond to their introduction) leads conservationists to develop new, more specific techniques. In similar ways, viral and bacterial-based controls have had limited success (although are still often proposed in conservation management, such as the planned carp herpesvirus release).
The better we understand invasive species and populations from a genetic perspective, the more informed our management efforts can be and the more likely we are to be able to adequately address the problem.
Managing invasive pest species
The impact of human settlement into new environments is exponentially beyond our direct influences. With our arrival, particularly in the last few hundred years, human migration has been an effective conduit for the spread of ecologically-disastrous species which undermine the health and stability of ecosystems around the globe. As such, it is our responsibility to Earth to attempt to address our problems: new genetic techniques is but one growing avenue by which we might be able to remove these invasive pests.
Beyond the apparent ethical and moral objections to the invasive nature of demanding genetic testing for Indigenous peoples, a crucial question is one of feasibility: even if you decided to genetically test for race, is this possible? It might come as a surprise to non-geneticists that actually, from a genetic perspective, race is not a particularly stable concept.
This is exponentially difficult for people who might have fewer sequenced ancestors or relatives; without the reference for genetic variation, it can be even harder to trace their genetic ancestry. Such is the case for Indigenous Australians, for which there is a distinct lack of available genetic data (especially compared to European-descended Australians).
The non-genetic components
The genetic non-identifiability of race is but one aspect which contradicts the rationality of genetic race testing. As we discussed in the previous post on The G-CAT, the connection between genetic underpinning and physicality is not always clear or linear. The role of the environment on both the expression of genetic variation, as well as the general influence of environment on aspects such as behaviour, philosophy, and culture necessitate that more than the genome contributes to a person’s identity. For any given person, how they express and identify themselves is often more strongly associated with their non-genetic traits such as beliefs and culture.
These factors cannot reliably be tested under a genetic framework. While there may be some influence of genes on how a person’s psychology develops, it is unlikely to be able to predict the lifestyle, culture and complete identity of said person. For Indigenous Australians, this has been confounded by the corruption and disruption of their identity through the Stolen Generation. As a result, many Indigenous descendants may not appear (from a genetic point of view) to be purely Indigenous but their identity and culture as an Indigenous person is valid. To suggest that their genetic ancestry more strongly determines their identity than anything else is not only naïve from a scientific perspective, but nothing short of a horrific simplification and degradation of those seeking to reclaim their identity and culture.
The non-identifiability of genetic race
The science of genetics overwhelmingly suggests that there is no fundamental genetic underpinning of ‘race’ that can be reliably used. Furthermore, the impact of non-genetic factors on determining the more important aspects of personal identity, such as culture, tradition and beliefs, demonstrates that attempts to delineate people into subcategories by genetic identity is an unreliable method. Instead, genetic research and biological history fully acknowledges and embraces the diversity of the global human population. As it stands, the phrase ‘human race’ might be the most biologically-sound classification of people: we are all the same.
It should come as no surprise to any reader of The G-CAT that I’m a firm believer against the false dichotomy (and yes, I really do love that phrase) of “nature versus nurture.” Primarily, this is because the phrase gives the impression of some kind of counteracting balance between intrinsic (i.e. usually genetic) and extrinsic (i.e. usually environmental) factors and how they play a role in behaviour, ecology and evolution. While both are undoubtedly critical for adaptation by natural selection, posing this as a black-and-white split removes the possibility of interactive traits.
Despite how important the underlying genes are for the formation of proteins and definition of physiology, they are not omnipotent in that regard. In fact, many other factors can influence how genetic traits relate to phenotypic traits: we’ve discussed a number of these in minor detail previously. An example includes interactions across different genes: these can be due to physiological traits encoded by the cumulative presence and nature of many loci (as in quantitative trait loci and polygenic adaptation). Alternatively, one gene may translate to multiple different physiological characters if it shows pleiotropy.
From an evolutionary standpoint again, epigenetics can similarly influence the ‘bang for a buck’ of particular genes. Being able to translate a single gene into many different forms, and for this to be linked to environmental conditions, allows organisms to adapt to a variety of new circumstances without the need for specific adaptive genes to be available. Following this logic, epigenetic variation might be critically important for species with naturally (or unnaturally) low genetic diversity to adapt into the future and survive in an ever-changing world. Thus, epigenetic information might paint a more optimistic outlook for the future: although genetic variation is, without a doubt, one of the most fundamental aspects of adaptability, even horrendously genetically depleted populations and species might still be able to be saved with the right epigenetic diversity.
Over the course of the (relatively brief) history of this blog, I’ve covered a number of varied topics. Many of these have been challenging to write about – either because they are technically-inclined and thus require significant effort to distill down to sensibility and without jargon; or because they address personal issues related to mental health or artistic expression. But despite the nature of these posts, this week’s blog has proven to be one of the most difficult to write, largely because it demands a level of personal vulnerability, acceptance of personality flaws and a potentially self-deprecating message. Alas, I find myself unable to ignore my own perceived importance of the topic.
It should come as no surprise to any reader, whether scientifically trained or not, that the expectation of scientific research is one of total objectivity, clarity and accuracy. Scientific research that is seen not to meet determined quotas of these aspects is undoubtedly labelled ‘bad science’. Naturally, of course, we aim to maximise the value of our research by addressing these as best as can be conceivably possible. Therein, however, lies the limitation: we cannot ever truly be totally objective, nor clear, nor accurate with research, and acceptance and discussion of the limitations of research is a vital aspect of any paper.
The imperfections of science
The basic underpinning of this disjunction lies with the people that conduct the science. Because while the scientific method has been developed and improved over centuries to be as objective, factual and robust as possible, the underlying researchers will always be plagued to some degree by subjectivism. Whether we consciously mean to or not, our prior beliefs, perceptions and history influence the way we conduct or perceive science (hopefully, only to a minor extent).
Additionally, one of the drawbacks of being mortal is that we are prone to making mistakes. Biology is never perfect, and the particularly complex tasks and ideas we assign ourselves to research inevitably involve some level of incorrectness. But while that may seem to fundamentally contradict the nature of science, I argue that is in fact not just a reality of scientific research, but also a necessity for progression.
It cannot be overstated that impostor syndrome is often the result of mental health issues and a high-pressure, demanding academic system, and rarely a rational perception. In many cases, we see only the best aspects of scientific research (both for academic students and the general public), a rose-coloured view of process. What we don’t see, however, is the series of failures and missteps that have led to even the best of scientific outcomes, and may assume that they didn’t happen. This is absolutely false.
The reality is that trying to predict the multitude of factors and problems one can run into when conducting an analysis is a monolithic task. Some aspects relevant to a particular dataset or analysis are unlikely to be discussed or clearly referenced in the literature, and thus difficult to anticipate. Problem solving is often more effective as a reactive, rather than proactive, measure by allowing researchers to respond to an issue when it arises instead of getting bogged down in the astronomical realm of “things that could possibly go wrong.”
Drawing on personal experience, this has led to literal months of reading and preparing data for running models only to have the first dozens of attempts not run or run incorrectly due to something as trivial as formatting. The lesson learnt is that I should have just tried to run the analysis early, stuffed it all up, and learnt from the mistakes with a little problem solving. No matter how much reading I did, or ever could do, some of these mistakes would never have been able to be explicitly predicted a priori.
Why failure is conducive to better research
While we should always strive to be as accurate and objective as possible, sometimes this can be counteractive to our own learning progress. The rabbit holes of “things that could possibly go wrong” run very, very deep and if you fall down them, you’ll surely end up in a bizarre world full of odd distractions, leaps of logic and insanity. Under this circumstance, I suggest allowing yourself to get it wrong: although repeated failures are undoubtedly damaging to the ego and confidence, giving ourselves the opportunity to make mistakes and grow from them ultimately allows us to become more productive and educated than if we avoided them altogether.
Speaking at least from a personal anecdote (although my story appears corroborated with other students’ experiences), some level of failure is critical to the learning process and important for scientific development generally. Although cliché, “learning from our mistakes” is inevitably one of the most effective and quickest ways to learn and allowing ourselves to be imperfect, a little inaccurate or at time foolish is conducive to better science.
Allow yourself to stuff things up. You’ll do it way less in the future if you do.
Note: For some clear, interesting presentations on the topic of de-extinction, and where some of the information for this post comes from, check out this list of TED talks.
The current conservation crisis
The stark reality of conservation in the modern era epitomises the crisis disciplinethat so often is used to describe it: species are disappearing at an unprecedented rate, and despite our best efforts it appears that they will continue to do so. The magnitude and complexity of our impacts on the environment effectively decimates entire ecosystems (and indeed, the entire biosphere). It is thus our responsibility as ‘custodians of the planet’ (although if I had a choice, I would have sacked us as CEOs of this whole business) to attempt to prevent further extinction of our planet’s biodiversity.
There’s one catch (well, a few really) with genetic rescue: namely, that one must have other populations to ‘outbreed’ with in order add genetic variation to the captive population. But what happens if we’re too late? What if there are no other populations to supplement with, or those other populations are also too genetically depauperate to use for genetic rescue?
Believe it or not, sometimes it’s not too late to save species, even after they have gone extinct. Which brings us from this (lengthy) introduction to this week’s topic: de-extinction. Yes, we’re literally (okay, maybe not) going to raise the dead.
Backbreeding: resurrection by hybridisation
You might wonder how (or even if!) this is possible. And to be frank, it’s extraordinarily difficult. However, it has to a degree been done before, in very specific circumstances. One scenario is based on breeding out a species back into existence: sometimes we refer to this as ‘backbreeding’.
This practice really only applies in a few select scenarios. One requirement for backbreeding to be possible is that hybridisation across species has to have occurred in the past, and generally to a substantial scale. This is important as it allows the genetic variation which defines one of those species to live on within the genome of its sister species even when the original ‘host’ species goes extinct. That might make absolutely zero sense as it stands, so let’s dive into this with a case study.
One of these species, Chelonoidis elephantopus, also known as the Floreana tortoise after their home island, went extinct over 150years ago, likely due to hunting and trade. However, before they all died, some individuals were transported to another island (ironically, likely by mariners) and did the dirty with another species of tortoise: C. becki. Because of this, some of the genetic material of the extinct Floreana tortoiseintrogressed into the genome of the still-living C. becki. In an effort to restore an iconic species, scientists from a number of institutions attempted to do what sounds like science-fiction: breed the extinct tortoise back to life.
When you saw the title for this post, you were probably expecting some Jurassic Parklevel ‘dinosaurs walking on Earth again’ information. I know I did when I first heard the term de-extinction. Unfortunately, contemporary de-extinction practices are not that far advanced just yet, although there have been some solid attempts. Experiments conducted using the genomic DNA from the nucleus of a dead animal, and cloning it within the egg of another living member of that species has effectively cloned an animal back from the dead. This method, however, is currently limited to animals that have died recently, as the DNA degrades beyond use over time.
One might expect that as genomic technologies improve, particularly methods facilitated by the genome-editing allowed from CRISPR/Cas-9 development, that we might one day be able to truly resurrect an extinct species. But this leads to very strongly debated topics of ethics and morality of de-extinction. If we can bring a species back from the dead, should we? What are the unexpected impacts of its revival? How will we prevent history from repeating itself, and the species simply going back extinct? In a rapidly changing world, how can we account for the differences in environment between when the species was alive and now?
There is no clear, simple answer to many of these questions. We are only scratching the surface of the possibility of de-extinction, and I expect that this debate will only accelerate with the research. One thing remains eternally true, though: it is still the distinct responsibility of humanity to prevent more extinctions in the future. Handling the growing climate change problem and the collapse of ecosystems remains a top priority for conservation science, and without a solution there will be no stable planet on which to de-extinct species.
Further to this, we can expand the site-frequency spectrum to compare across populations. Instead of having a simple 1-dimensional frequency distribution, for a pair of populations we can have a grid. This grid specifies how often a particular allele occurs at a certain frequency in Population A and at a different frequency in Population B. This can also be visualised quite easily, albeit as a heatmap instead. We refer to this as the 2-dimensional SFS (2DSFS).
The same concept can be expanded to even more populations, although this gets harder to represent visually. Essentially, we end up with a set of different matrices which describe the frequency of certain alleles across all of our populations, merging them together into the joint SFS. For example, a joint SFS of 4 populations would consist of 6 (4 x 4 total comparisons – 4 self-comparisons, then halved to remove duplicate comparisons) 2D SFSs all combined together. To make sense of this, check out the diagrammatic tables below.
The different forms of the SFS
Which alleles we choose to use within our SFS is particularly important. If we don’t have a lot of information about the genomics or evolutionary history of our study species, we might choose to use the minor allele frequency (MAF). Given that SNPs tend to be biallelic, for any given locus we could have Allele A or Allele B. The MAF chooses the least frequent of these two within the dataset and uses that in the summary SFS: since the other allele’s frequency would just be 2N – the frequency of the other allele, it’s not included in the summary. An SFS made of the MAF is also referred to as the folded SFS.
Alternatively, if we know some things about the genetic history of our study species, we might be able to divide Allele A and Allele B into derived or ancestral alleles. Since SNPs often occur as mutations at a single site in the DNA, one allele at the given site is the new mutation (the derived allele) whilst the other is the ‘original’ (the ancestral allele). Typically, we would use the derived allele frequency to construct the SFS, since under coalescent theory we’re trying to simulate that mutation event. An SFS made of the derived alleles only is also referred to as the unfolded SFS.
Applications of the SFS
How can we use the SFS? Well, it can moreorless be used as a summary of genetic variation for many types of coalescent-based analyses. This means we can make inferences of demographic history (see here for more detailed explanation of that) without simulating large and complex genetic sequences and instead use the SFS. Comparing our observed SFS to a simulated scenario of a bottleneck and comparing the expected SFS allows us to estimate the likelihood of that scenario.
The SFS can even be used to detect alleles under natural selection. For strongly selected parts of the genome, alleles should occur at either high (if positively selected) or low (if negatively selected) frequency, with a deficit of more intermediate frequencies.
Adding to the analytical toolbox
The SFS is just one of many tools we can use to investigate the demographic history of populations and species. Using a combination of genomic technologies, coalescent theory and more robust analytical methods, the SFS appears to be poised to tackle more nuanced and complex questions of the evolutionary history of life on Earth.