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.

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Content last updated: 17/07/2006

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