Pressing Ctrl-Z on Life with De-extinction

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 discipline that 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.

Human CEO example
“….shit.”

If you’re even remotely familiar with this blog, then you would have been exposed to a number of different techniques, practices and outcomes of conservation research and its disparate sub-disciplines (e.g. population genetics, community ecology, etc.). Given the limited resources available to conserve an overwhelming number of endangered species, we attempt to prioritise our efforts towards those most in need, although there is a strong taxonomic bias underpinning them.

At least from a genetic perspective, this sometimes involves trying to understand the nature and potential of adaptation from genetic variation (as a predictor of future adaptability). Or using genetic information to inform captive breeding programs, to allow us to boost population numbers with minimal risk of inbreeding depression. Or perhaps allowing us to describe new, unidentified species which require their own set of targeted management recommendations and political legislation.

Genetic rescue

Yet another example of the use of genetics in conservation management, and one that we have previously discussed on The G-CAT, is the concept of ‘genetic rescue’. This involves actively adding new genetic material from other populations into our captive breeding programs to supplement the amount of genetic variation available for future (or even current) adaptation. While there traditionally has been some debate about the risk of outbreeding depression, genetic rescue has been shown to be an effective method for prolonging the survival of at-risk populations.

super-gene-genetic-rescue-e1549973268851.jpg
How my overactive imagination pictures ‘genetic rescue’.

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.

Necroconservaticon
Your textbook guide to de-extinction. Now banned in 47 countries.

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.

I’m sure you’ll recognise (at the very least, in name) these handsome fellows below: the Galápagos tortoise. They were a pinnacle in Charles Darwin’s research into the process of evolution by natural selection, and can live for so long that until recently there had been living individuals which would have been able to remember him (assuming, you know, memory loss is not a thing in tortoises. I can’t even remember what I had for dinner two days ago, to be fair). As remarkable as they are, Galápagos tortoises actually comprise 15 different species, which can be primarily determined by the shape of their shells and the islands they inhabit.

Galapagos island and tortoises
A map of the Galápagos archipelago and tortoise species, with extinct species indicated by symbology. Lonesome George was the last known living member of the Pinta Island tortoise, C. abingdonii for reference. Source: Wikipedia.

One of these species, Chelonoidis elephantopus, also known as the Floreana tortoise after their home island, went extinct over 150 years ago, likely due to hunting and tradeHowever, 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 tortoise introgressed 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.

By carefully managing and selectively breeding captive individuals , progressive future generations of the captive population can gradually include more and more of the original extinct C. elephantopus genetic sequence within their genomes. While a 100% resurrection might not be fully possible, by the end of the process individuals with progressively higher proportion of the original Floreana tortoise genome will be born. Although maybe not a perfect replica, this ‘revived’ species is much more likely to serve a similar ecological role to the now-extinct species, and thus contribute to ecosystem stability. To this day, this is one of the closest attempts at reviving a long-dead species.

Is full de-extinction possible?

When you saw the title for this post, you were probably expecting some Jurassic Park level ‘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.

The same methods have been attempted for some extinct animals, which went extinct relatively recently. Experiments involving the Pyrenean ibex (bucardo) were successful in generating an embryo, but not sustaining a living organism. The bucardo died 10 minutes after birth due to a critical lung condition, as an example.

The challenges and ethics of de-extinction

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?

Deextinction via necromancy figure
The Chaotic Neutral (?) approach to de-extinction.

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.

de-extinction meme
You bet we’re gonna make a meme months after it’s gone out of popularity.

Rescuing the damselfish in distress: rescue or depression?

Conservation management

Managing and conserving threatened and endangered species in the wild is a difficult process. There are a large number of possible threats, outcomes, and it’s often not clear which of these (or how many of these) are at play at any one given time. Thankfully, there are also a large number of possible conservation tools that we might be able to use to protect, bolster and restore species at risk.

Using genetics in conservation

Naturally, we’re going to take a look at the more genetics-orientated aspects of conservation management. We’ve discussed many times the various angles and approaches we can take using large-scale genetic data, some of which include:
• studying the evolutionary history and adaptive potential of species
• developing breeding programs using estimates of relatedness to increase genetic diversity
identifying and describing new species for government legislation
• identifying biodiversity hotspots and focus areas for conservation
• identifying population boundaries for effective management/translocations

Genetics flowchart.jpg
An example of just some of the conservation applications of genetics research that we’ve talked about previously on The G-CAT.

This last point is a particularly interesting one, and an area of conservation research where genetics is used very often. Most definitions of a ‘population’ within a species rely on using genetic data and analysis (such as Fst) to provide a statistical value of how different groups of organisms are within said species. Ignoring some of the philosophical issues with the concept of a population versus a species due to the ‘speciation continuum’ (read more about that here), populations are often interpreted as a way to cluster the range of a species into separate units for conservation management. In fact, the most commonly referred to terms for population structure and levels are evolutionarily-significant units (ESUs), which are defined as a single genetically connected group of organisms that share an evolutionary history that is distinct from other populations; and management units (MUs), which may not have the same degree of separation but are still definably different with enough genetic data.

Hierarchy of structure.jpg
A diagram of the hierarchy of structure within a species. Remember that ESUs, by definition, should be evolutionary different from one another (i.e. adaptively divergent) whilst MUs are not necessarily divergent to the same degree.

This can lead to a particular paradigm of conservation management: keeping everything separate and pure is ‘best practice’. The logic is that, as these different groups have evolved slightly differently from one another (although there is often a lot of grey area about ‘differently enough’), mixing these groups together is a bad idea. Particularly, this is relevant when we consider translocations (“it’s never acceptable to move an organism from one ESU into another”) and captive breeding programs (“it’s never acceptable to breed two organisms together from different ESUs”). So, why not? Why does it matter if they’re a little different?

Outbreeding depression

Well, the classic reasoning is based on a concept called ‘outbreeding depression’. We’ve mentioned outbreeding depression before, and it is a key concept kept in mind when developing conservation programs. The simplest explanation for outbreeding depression is that evolution, through the strict process of natural selection, has pushed particularly populations to evolve certain genetic variants for a certain selective pressure. These can vary across populations, and it may mean that populations are locally adapted to a specific set of environmental conditions, with the specific set of genetic variants that best allow them to do this.

However, when you mix in the genetic variants that have evolved in a different population, by introducing a foreign individual and allowing them to breed, you essentially ‘tarnish’ the ‘pure’ gene pool of that population with what could be very bad (maladaptive) genes. The hybrid offspring of ‘native’ and this foreign individual will be less adaptive than their ‘pure native’ counterparts, and the overall adaptiveness of the population will decrease as those new variants spread (depending on the number introduced, and how negative those variants are).

Outbreeding depression example figure.jpg
An example of how outbreeding depression can affect a species. The original red fish population is not doing well- it is of conservation concern, and has very little genetic diversity (only the blue gene in this example). So, we decide to introduce new genetic diversity by adding in green fish, which have the orange gene. However, the mixture of the two genes and the maladaptive nature of the orange gene actually makes the situation worse, with the offspring showing less fitness than their preceding generations.

You might be familiar with inbreeding depression, which is based on the loss of genetic diversity from having too similar individuals breeding together to produce very genetically ‘weak’ offspring through inbreeding. Outbreeding depression could be thought of as the opposite extreme; breeding too different individuals introduced too many ‘bad’ alleles into the population, diluting the ‘good’ alleles.

Inbreeding vs outbreeding figure.jpg
An overly simplistic representation of how inbreeding and outbreeding depression can reduce overall fitness of a species. In inbreeding depression, the lack of genetic diversity due to related individuals breeding with one another makes them at risk of being unable to adapt to new pressures. Contrastingly, adding in new genes from external populations which aren’t fit for the target population can also reduce overall fitness by ‘diluting’ natural, adaptive allele frequencies in the population.

Genetic rescue

It might sound awfully purist to only preserve the local genetic diversity, and to assume that any new variants could be bad and tarnish the gene pool. And, surprisingly enough, this is an area of great debate within conservation genetics.

The counterpart to the outbreeding depression concerns is the idea of genetic rescue. For populations with already severely depleted gene pools, lacking the genetic variation to be able to adapt to new pressures (such as contemporary climate change), the situation seems incredibly dire. One way to introduce new variation, which might be the basis of new adaptation, bringing in individuals from another population of the same species can provide the necessary genetic diversity to help that population bounce back.

Genetic rescue example figure.jpg
An example of genetic rescue. This circumstance is identical to the one above, with the key difference being in the fitness of the introduced gene. The orange gene in this example is actually beneficial to the target population: by providing a new, adaptive allele for natural selection to act upon, overall fitness is increased for the red fish population.

The balance

So, what’s the balance between the two? Is introducing new genetic variation a bad idea, and going to lead to outbreeding depression; or a good idea, and lead to genetic rescue? Of course, many of the details surrounding the translocation of new genetic material is important: how different are the populations? How different are the environments (i.e. natural selection) between them? How well will the target population take up new individuals and genes?

Overall, however, the more recent and well-supported conclusion is that fears regarding outbreeding depression are often strongly exaggerated. Bad alleles that have been introduced into a population can be rapidly purged by natural selection, and the likelihood of a strongly maladaptive allele spreading throughout the population is unlikely. Secondly, given the lack of genetic diversity in the target population, most that need the genetic rescue are so badly maladaptive as it is (due to genetic drift and lack of available adaptive alleles) that introducing new variants is unlikely to make the situation much worse.

Purging and genetic rescue figure.jpg
An example of how introducing maladaptive alleles might not necessarily lead to decreased fitness. In this example, we again start with our low diversity red fish population, with only one allele (AA). To help boost genetic diversity, we introduce orange fish (with the TT allele) and green fish (with the GG allele) into the population. However, the TT allele is not very adaptive in this new environment, and individuals with the TT gene quickly die out (i.e. be ‘purged’). Individual with the GG gene, however, do well, and continue to integrate into the red population. Over time, these two variants will mix together as the two populations hybridise and overall fitness will increase for the population.

That said, outbreeding depression is not an entirely trivial concept and there are always limitations in genetic rescue procedures. For example, it would be considered a bad idea to mix two different species together and make hybrids, since the difference between two species, compared to two populations, can be a lot stronger and not necessarily a very ‘natural’ process (whereas populations can mix and disjoin relatively regularly).

The reality of conservation management

Conservation science is, at its core, a crisis discipline. It exists solely as an emergency response to the rapid extinction of species and loss of biodiversity across the globe. The time spent trying to evaluate the risk of outbreeding depression – instead of immediately developing genetic rescue programs – can cause species to tick over to the afterlife before we get a clear answer. Although careful consideration and analysis is a requirement of any good conservation program, preventing action due to almost paranoid fear is not a luxury endangered species can afford.