Tom Clarke has a background in zoology. After leaving the lab he worked on science radio and television programmes in the United States. He now writes about the latest research in science and technology for Nature magazine's 'Nature News Service'.
Has Human Evolution Stopped?
Between three and five million years ago the forces of nature drove our ape-like ancestors down from the safety of the trees and made them stand on their own two feet. These upright apes were then sculpted by natural selection into lankier, less hairy, brainy creatures.
Later, other natural forces, perhaps climate change, disease or even war relegated our cousins the Neanderthals to the evolutionary scrap heap while our species, Homo sapiens survived — but only just.
In the 500 thousand or so years we've been strolling the Earth Homo sapiens have been continually feeling the force of natural selection too. We were nearly snuffed out by an ice age and whole civilisations disappeared beneath floodwaters, volcanic ash or were wiped out by horrific diseases. Only those of us with good genes and good fortune survived to reproductive age and passed those genes on.
Now almost everyone in the developed world lives past reproductive age and improving healthcare and infrastructure in the developing world will surely mean that poorer countries will enjoy the same luxury. As people aren't dying until after they reproduce, bad genes and harmful mutations are passed on to the next generation. This surely flies in the face of natural selection — the survival of the fittest — meaning human evolution has come grinding to a halt?
In my opinion, no. In the developing world (which is most of the world) vast numbers of children die because of natural disasters, diseases and warfare —the same things that were killing our ancestors 500,000 thousand years ago. You only have to look to the HIV pandemic or drought induced famine for a very modern example of nature's selective forces at work. The case is perhaps harder to argue for those of us living in a sturdy house in a safe leafy suburb, with clean drinking water and private health care. Infant mortality is a thing of the past, major diseases are treatable and natural disasters largely avoidable, so the merciless selective forces of nature are something of an irrelevance.
Certainly, but that doesn't necessarily mean human evolution has stopped. I'd argue that technologically developed societies have merely slowed evolution down. But we can only keep nature at bay for so long. Take disease as an example; HIV is far from under control in the developed world and many experts predict that old enemies like influenza and tuberculosis are poised to make a comeback. After enjoying a century or two of the good life, with "bad genes" accumulating in our population, we will be a very soft target for a new disease outbreak or an unforeseen natural disaster. If our technologies fail to protect us against these forces of nature our genetic heritage could fail us too, meaning human evolution will return with a vengeance.
Dr Adam Eyre-Walker is an evolutionary biologist at the University of Sussex. Dr Eyre-Walker recently published a paper investigating the rise of harmful mutations in the human population. He believes that human evolution is still happening, although natural selection is relaxed in the developed world.
What is a ‘harmful mutation’ and what results have you got from your research into them?
A harmful mutation is a mutation which reduces the probability of producing offspring, so that it either reduces the probability of surviving to reproductive age or the probability of actually being fertile. Most mutations are thought to be spontaneous, each generation your DNA has to be replicated several times and it’s in during that process most of the mutations are thought to occur.
We’ve recently estimated the rate of these harmful mutations since we split from chimpanzees about 6 million years ago and we came up with an estimate of about 2 harmful mutations occurring per genome per generation, which is the highest that’s ever been estimated in any organism so far and that’s probably and underestimate. It means that we are all carrying maybe up to 1000 harmful mutations.
Hasn’t changing cultural attitude also affected natural selection?
Yes, in the past some couples would have many, many children – you could call those ‘ultra-fertile’ couples - and some would have none. Now, however, variation in family size is quite small, most couples now have 2 or 3 children because it’s no longer behaviourally the thing to do to have many. Therefore the ultra-fertile couples, or the potentially ultra fertile couples, have essentially vanished, they no longer have an advantage over the less fertile couples. And therefore selection has been relaxed on fertility.
Why do genetic diseases still exist?
There are many genetic diseases around largely because of recurrent mutation, so you’re just getting mutations always coming into the human population and those mutations will cause an individual to have lower fertility or something like that, but they may still have offspring, they may still have children who have that mutation. Furthermore, many of the genetic diseases we see in our population have late onset, so they affect the individual basically after their prime reproductive years and therefore natural selection is really not acting upon those mutations.
And finally there are the occasional examples where it may be the case that the mutation has some advantage in some environments, and the classic example of that is sickle cell anaemia, where the mutation makes you immune, or partially immune, to malaria but in some cases it will kill an individual. It’s also been hypothesised that diabetes might have been an ancient adaptation to starvation, so again that’s a genetic disease which in the past or in a different environment may have been advantageous but in a modern setting has become harmful to us.
How much do infectious diseases impact on evolution?
It’s clear infectious diseases have been a major force in evolution both in the past and in our current time. A dramatic example is the 1918 outbreak of influenza known as the Spanish influenza, which killed between 20 and 40 million people worldwide. And of course with the decline in efficiency of antibiotics many, many bacterial pathogens will again become very potent forces driving evolution, and individuals who are resistant to those are going to better than those who are not. So I believe that they will be a major force. You said mutations are increasing, and this is especially due to modern medicine.
Could we be facing mutational meltdown?
Mutational meltdown is the process by which as harmful mutations accumulate in a population, those harmful mutations, because they reduce things like fertility, can actually lead to a reduction in the population size. As soon as the population size has reduced, that actually increases the rate at which harmful mutations accumulate in the population. And of course as more accumulate the population size becomes depressed, that leads to the faster accumulation of harmful mutations and you can reach a critical point where those two processes basically snowball, you have positive feedback and eventually the population just becomes extinct.
Whether we are likely to go through that mutational meltdown I very much doubt it. It’s much more likely that what will happen is that we accumulate mutations through improved living conditions, modern medicine, and then if those sort of props are removed then we may find ourselves in a rather sorry state. But it’s always very important to remember that this is only true of the developed world. The developing world natural selection is much much more potent, selection is not relaxed anything like to the same extent as it is in the developed world.
Is it possible to argue human evolution has stopped?
I don’t think human evolution has stopped, for a number of reasons. First of all it’s alive and kicking in the developing world. Secondly, even within our own developed world there are still natural selection is working through some of these infectious diseases and is likely to continue to work. And finally, even if natural selection was completely removed evolution would continue because evolution is just the process of change, so if we relax natural selection then we would start to accumulate harmful mutations, or mutations which were harmful in the past, and that would lead to things like a slow erosion of fertility, a decrease in survival rates, and things like that.
Dr Martin Westwell is a chemist at the University of Oxford who has carried out research into new and resistant forms of bacteria. He believes that in a few years' time, before new antibiotics are available to combat them, there will be many more harmful kinds of bacteria around. Thus diseases could 'bite back' and have a significant effect on human evolution once again.
How important has the discovery of antibiotics been in controlling infectious disease?
When antibiotics was introduced in the 1950s it was a revolution. Where once people were going into hospital and dying, now they were just treated with an antibiotic, sent home and they were fine. And that was the state of play for a number of years, right through the ‘60s and ‘70s, new antibiotics were being introduced and infectious diseases just became trivial, people didn’t worry about them.
But what happened is through the ‘70s while things were so good pharmaceutical companies and researchers weren’t looking for new antibiotics, they didn’t think it was such a priority. That’s meant that now we have a serious situation where pharmaceutical companies have estimated that for a few years in our hospitals we’re going to be going back to the bad old days before penicillin when trivial infections - cuts on the hands, surgical wounds, burns, things like that - will kill people because of bacteria that are resistant to all of the antibiotics that we’ve always had before.
Could you explain how our increasingly sanitised Western world may also be a cause of increased disease?
Before penicillin children’s immune systems were fantastic, they’d come against all this dirt, all this bacteria, all through their lives and they’d build up a really good immune system. Now we live in a sterile, sanitised environment and we think we’re doing good for our kids by doing this, but what it actually means is that their immune system never gets challenged, it never gets to work, it never learns how to fight off these bugs. And so if they get an infection that’s resistant to antibiotics their immune system isn’t going to be as good as the kids from a few generations ago who could fight off these bugs.
How will the problem of resistant bacteria impact on the process of selection?
This effect has only occurred over a few generations and so the selectional pressure as far as evolution is concerned hasn’t been very great. But if this problem continues and we don’t come up with new antibiotics and our immune systems continue to be as bad as they are, then we can see in a few generations time selectional pressure will be there, because lots of people will be dying from infectious diseases, including antibiotic-resistant bacteria.
How has modernisation affected the spread of disease?
One of the important factors for the diseases of the future is that of our changes in lifestyle. If you compare our lifestyle to that in the 3rd World or to lifestyles years ago, you can see that those changes have really brought on some diseases. So, for example, viruses that may have been in the world in a remote area for a long time and never broken out, now with communications and the changes in the way that people live, diseases like HIV, have managed to get a global hold and can spread around the world. And in the future, if we ever combat HIV, there will be new diseases, because these bacteria and these viruses will always come up with new ways of getting into human being and killing people, because that’s what these bugs need to do in order for them to survive themselves.
But hasn’t modernisation also given us the tools with which to fight diseases?
Humans of course think that they’re very clever because of all the technology that we come up with and all the ways that we have of getting around these diseases, but really that’s a very complacent position. In the 1960s the Surgeon General of the US said ‘it’s time to close the book on infectious diseases’. He thought that we had such an arsenal of weapons against these bugs that no matter what they did we’d always be able to come up with a way of defeating them. But of course the bacteria and the viruses are evolving, and they use this power of evolution to overcome everything that we do. And I think we’re just starting to realise now that even if we get past this problem where antibiotics are going to start to become useless, we’re still going to have to continue this war against infectious diseases, it’s really going to go on for ever and ever.
Could you put the problem of infectious diseases into the wider context of human evolution?
If you think about diseases like the Bubonic Plague, of course that killed millions of people in Europe and that could be seen as a selectional pressure – people were dying, the ones who had resistance to the plague survived and so essentially evolved, or took steps forward in human evolution at least, as they overcame the disease. Since the introduction of penicillin what’s happened is there’s been no selectional pressure from infectious diseases, we’ve always been able to overcome them, the people that have been killed have been in a minority. But if we really can’t find new ways to overcome viruses and bacteria that can kill people, in a few generations time that will mean real selectional pressure, because people who can’t overcome these diseases themselves with their own immune system will die, and of course that’s natural selection which could drive forward human evolution in the future.
Dr Ian Hastings is a scientist at the Liverpool School of Tropical Medicine. He believes that 'reproductive compensation' is having a significant effect on the gene pool.
Could you explain reproductive compensation?
Think back to maybe 100 years ago where families tended to be very large and a mother would reproduce as quickly as she could. Now, imagine she had 13 children, that’s as many as she could physically produce, and one of them died of genetic disease, then that dead child has gone and taken his or her genes with them. There’s no capacity within the mother to produce another child. Contrast that with the modern situation, where people plan to have maybe 2 or 3 children – if one of those children die of a genetic disease, it’s well within the capacity of the mother to produce another child to compensate for that dead child, and the tendency is for that replacement child to be carrying the gene. In fact, if it’s a sex linked recessive disease like muscular dystrophy there’s a one in three chance that the replacement child will carry a copy of the mutated gene, and as a consequence of this the frequency of the mutated gene increases in the next generation.
What does this increase of mutated genes mean for evolution?
What are the consequences of that for long term human evolution? I think that depends on how you view the human gene pool. There is a tendency to view humans as being at the pinnacle of evolution, or maybe even races as being the pinnacle of evolution, and that any dilution of that gene pool would be catastrophic, we’d fall off a pedestal in other words. But evolutionary geneticists are far more relaxed about it, they look at physical aspects of humans and say they’re not particularly fast, they’re not particularly strong, they survive in the modern world because of their culture, and it’s culture rather than genetics that’s the important thing. We also now know that most people in the population carry 2 or 3 lethal recessive mutations, so it’s not particularly good gene pool anyway and if it degrades a little bit, well, probably that’s not going to have huge consequences for human evolution, at least not over our life spans and the life spans of our great-great-great-grandchildren.
We can quantify this increase of frequency of genes in the next generation mathematically, if we assume that historically there was no reproductive compensation and that now we do compensate. So, for recessive genes the frequency will rise by about 0.5% per generation, but for sex-linked lethal genes the frequency change will be very large, it may increase by 15-20% in the first generations, and over the first few generations will increase maybe 30-50%. It will then stabilise at a new equilibrium value.
How is modern medicine affecting evolution?
So mutations inevitably occur and come into the human population, the question is what happens to them thereafter. Now, in traditional evolutionary genetics of animals and plants the only way they’re eliminated is if the individual dies or fails to reproduce. Neither option is particularly attractive to human beings, so we’ve developed medical techniques to try and cope with these mutations. There are two real ways of trying to deal with them: the first is gene therapy, they may well try in the future to reverse these original mutations; and the other way to do it is just to treat the symptoms of the disease. Haemophilia is a good example of something which was lethal up to fairly recently and is now fairly easily treated by modern medicine.
Do genetic diseases or medicine have the upper hand?
Historically infectious diseases have been an important selective pressure on human populations. Biologically they always had the upper hand – they had big population sizes and they had a very rapid population growth, and they always kind of stayed one step ahead of humans. Now the situation has reversed, rather than genetic evolution we’re in the situation of cultural evolution, and medicine now can evolve more quickly than the mutations can. So, at least long term, we are optimistic that we should stay ahead of diseases as a selective element.
How will reproductive technology affect the rate of mutation?
Sex-linked recessive diseases such as muscular dystrophy (DMD) only affect boys. So we can anticipate the situation whereby families can choose the sex of their offspring, and if the mother carries a copy of the DMD gene, they may well decide just to have girls. Now, if that does occur because the girls tend to be carriers of DMD, then the frequency of the gene will rise quite rapidly within the population.
Does all this talk of genetic change need to be put into some sort of context?
Yes, the critical point to note is that evolutionary geneticists tend to think in the timescale of generations - a human generation will be maybe 25 years. Now, our timescale is usually hundreds or thousands of generations, which if you convert that to real time in humans is a vast amount of time. Even ten human generations, which is very quick on an evolutionary timescale, would be 250 years. So if you think back to 250 years ago and the state of human society then, you realise how slowly genetic processes occur compared to cultural evolution.
Professor Laurence Hurst is an evolutionary geneticist at the University of Bath. He is an expert on the relationship between sex/age of parenting and the rate of harmful mutations in the population.
What is the trend for age of reproduction and how is this affecting mutation rate?
There have been major trends over the last 20 years in the age at which men and women are reproducing. So for example, at the turn of the 19th century one would have seen women and men start reproducing at age 20, finishing reproducing about age 40 or so and having a large family, with more or less continuous reproduction within that time space. Now there’s a much, much stronger trend for both men and women to start reproducing later, so 35, but still end reproduction at about age 40.
This matters for two different reasons. Firstly, we know, for example, that when it comes to certain birth disorders such as Downs Syndrome there is a very major effect of the age at which women reproduce on the probability that a child will be affected. These conditions are ones in which the infants have an extra chromosome, so rather than the normal 46 they may have 47. Downs, for example, is a case where you have 3 copies of Chromosome 21, we call it a trisomy. We’re usually disomic, two copies, but these individuals are trisomic for this chromosome. If you’re reproducing age 35 through to 40, you’re automatically more likely to have a trisomic offspring than you are at age 20. Now, that per se is not actually necessarily going to affect evolution, because your average trisomic individual actually dies in utero - most of these a woman wouldn’t know, they would appear as late periods and they might not even have known they were pregnant. In addition, the individuals that are born are typically sterile, so it’s not going to affect necessarily the gene pool greatly.
A much bigger effect in that regard is that of male age of reproduction. This is because older men don’t necessarily contribute more trisomic individuals, but the mutation rate is very heavily dependent on the age at which males reproduce: we have evidence from a variety of sources that older men end up leaving many more mutations. If we have a rate ancestrally which may be of the order 2-4 genomic deleterious mutations per generation, we might expect that with males reproducing later - possibly now 30 through to 40 - this figure might go more to the domain of 8-12, or even possibly higher, so what we expect to see is many more individuals turning up in hospital with genetic disorders.
What effect might later reproduction have on women in the long term?
There’s one interesting conjecture which may yet hold to be true, this is that there may well be selection operating on the age of menopause. Now, if you imagine women only reproducing between the ages of 35 and 40, but some had menopause aged 36 or something like that, then what you’re going to expect – and we have to assume there’s heritable variation on the age of menopause – is that a number of women, come 36, 37, are going to want to be having children are not able to, whereas those who are menopausing later are capable of having children.
The net effect of this, we would then expect, would be that the age of menopause would be kicked back further and further, because the gene pool would be being changed by the fact that those women who would have had menopause early are the ones who are now not reproducing. So we might expect fairly strong selection on the age of menopause.
What will be the effect of modern medicine on the increase of mutation and therefore on selection?
For just about everything we might say about the consequences of reproducing later, the other great trend that we see at the moment is a remarkable change in human healthcare. There are techniques, IVF for example, whereby one can aid older women in having children where previously without such techniques they wouldn’t have been able to. But that aside there are actually very much simpler techniques now, which almost certainly are going to affect the perameters. One of these is a simple test using a chemical known as inhibin. Inhibin exists in women’s bodies and decays over time in the amount that we find it is at zero level at age menopause, much higher much earlier. So we can in principle do a simple test, work out what the levels of inhibin are, tell a 20-yr-old that by the age of 35 she’s going to run out of eggs, and that therefore is going to change her perception of when she’s going to want to reproduce. So, when that sort of test becomes available, we’re going to expect to see many fewer women turning up at the fertility clinics aged 35-40 wondering why they can’t get pregnant. If that happens this selection on the menopause then goes away.
This is in fact a very general trend, that advances in healthcare take selection away from the human population. A nice example of this comes if we compare the probability of a young child dying as a function of its birth weight at around 1900 through to what we now see. At about 1900 there was an absolutely optimal birth weight - either side of that, if you were too large or if you were too small, your chances of dying were very much higher. However, nowadays, because of advances in healthcare, we don’t see this pattern at all – we can keep very small babies alive, we can keep very large babies alive. So healthcare is having major effects in effectively taking away selective deaths, individuals who would’ve died because of bad genes, for want of a better word, are now being kept alive. And we’re all being kept alive much later as well. So at that level we would expect that in fact natural selection is not having its effects, in that sense evolution isn’t going on. There is evolution going on in the background, mutations are still accumulating, it’s just not natural selection, it’s not making us better, if anything it’s making us worse.
The potential use of gene therapy will also have an impact – could you explain?
A potential effect of later male reproduction is the gene pool as a whole having many more deleterious recessives, that is, not seen now, but sitting making trouble in a few years time. Well, recent advances in gene technology promise a different future. In principle the idea, so-called gene therapy, is to identify the gene that you should have as opposed to the mutation that you actually have and attempt to replace one by the other, thereby ameliorating the disease.
Now, gene therapy technology as a whole, while it clearly has enormous potential, has yet to be proven and it’s meeting a number of stumbling blocks. However, it is undergoing trials in the states at the moment. There are two forms of gene therapy we can think about in principle – one is one where we simply take an infected individual and try to replace, let’s say, the liver cells with liver cells that contain the good version of the gene - the non-cystic fibrosis form of the cystic fibrosis gene, for example. Now, that’s fine and largely, to my mind, defendable. The harder issue comes where we talk about so-called germline therapy, here we’re actually affecting the mutations that an individual not only has but will in fact transmit. Affecting these is going to affect the gene pool, and that can potentially therefore have a major affect on evolution. And here, therefore, we’re hitting very tricky moral grounds as to whether we should in fact ever interfere in that way.
How has globalisation impacted on evolution?
One of the big changes that’s occurred within the 20th century and is almost certainly going to carry on is globalisation of movement of people and of plants and animals and so on. This is going to have, or at least potentially have big consequences for humans. It means rather than being a population which is highly sub-structured - there’s us here in Europe and others in America and others in Africa, with people existing and marrying only locally – now people from Brazil will marry into European society, and so on. This has had big consequences for the nature of evolution.
Most notably what it means is that if ever there was a really great mutation out there, an advantageous mutation, something that makes us even better, it now has the potential to move through the human population much faster. Before, let’s say if we had a mutation which may have made you unbelievably fit starting off in Brazil, it almost certainly would’ve been restricted to a small few tribes within Brazil. Now, however, because of developments in mass transportation, that great mutation can tomorrow be moved from Brazil to GB, that person just has to settle down, have kids and it’s then starting to spread within the British population.
But there is also a big downside and that is that with all this movement we’re also bringing diseases which we’ve never seen before and can potentially be a very harmful and very important selective force. The most notable example of this historically is probably the Spanish Conquistadors, who managed to dominate large amounts of central and Southern America largely because they brought viruses with them, not deliberately obviously, they just had a flu virus which decimated the local population which wasn’t adapted to it.
What is the likelihood that humans will speciate? Every species that we know about has come from another species, and the process by which one lineage splits into two is the process of speciation. There’s a variety of models for how this works, but the dominant model says something to the effect that you take the population, you split it into two and over time changes will accumulate which stop those two reproducing with one another – they may try, but they will fail. So, for example, why we call humans one species and chimps another is if you try reproducing one through to the other, either it won’t work because the machinery of copulation won’t work, or because individuals aren’t interested in doing this, or because even if they do it the offspring that come out are sterile. So this is the process of speciation.
Now, we can ask a simple question: is it likely that in the near future humans are going to speciate? Are we going to see, for example, a different species of human coming along in Mongolia to what you see in Brazil? And you could imagine that such a thing is entirely possible – not in the timescales that we’re looking at, we’re talking about millions of years here, not the last 20 years. And of course one can only speculate here, but again the big changes in mass transportation, has some consequences for this. If we were to take a population that had been split apart, but allowed free movement between the two sides, between Brazil and Mongolia, then we wouldn’t get the differences between the two lineages, we wouldn’t get speciation. So, one of the consequences might well be that humans as a species are less likely to speciate then just about any other species we’ve seen previously, because they are so capable of moving genes from one part of the distant population to another part of the population, therefore preventing any two parts of the population becoming very much different. However, call me back in 3 million years time, because I may well be wrong on that one.