Get the Mosquitoes!

Some flour beetles carry a gene called Medea. Their offspring look normal as larvae but, around the time of hatching, half the females become listless, then paralysed; and then they die. No one knows how it works, but the female offspring that inherit a copy of the gene are protected from the poison it uses, while those that don’t are killed by it.

Medea has evolved thanks to sexual reproduction. Nearly all animals carry two copies of each chromosome (in plants and fungi the situation is more complicated, but the principles are largely the same). Some genes are present in a different version on each copy, which is why someone can carry the gene that causes cystic fibrosis or sickle-cell anaemia, but not suffer from the disease. These genes are recessive, which means their effects show themselves only if they are present on both copies of a chromosome. When eggs and sperm are created, however, the genome is first shuffled to form a new combination of genes from both parents, and then halved, so that only one copy of each chromosome from each parent makes it into the next generation. This is why, when two carriers of the cystic fibrosis gene reproduce, there is only a 25 per cent likelihood of their children suffering from the disease (and a 50 per cent chance of their being carriers).

Most genes put up with this reproductive lottery: the evolutionary cost of being absent from half of the next generation looks to have been outweighed by the benefits of sexual reproduction as a quick way to bring good genes together and weed bad ones out. But any gene that can rig the lottery, so that it gets into more than half its carrier’s offspring, will spread. These genes are not merely selfish in Richard Dawkins’s sense of being selected to out-compete different versions of themselves in the population: they are ruthless because, as in the case of Medea, they can spread even though their effects are strongly detrimental to the evolutionary interests of the organisms that carry them. Austin Burt and Robert Trivers call such genes ‘selfish genetic elements’.

That such elements should evolve is no more surprising than that viruses should exist. An organism results from the co-operation of a set of genes, and natural selection favours those organisms whose genes best equip them to reproduce. But, like co-operative systems everywhere, the genome is vulnerable to invasion by freeloaders. Sexual reproduction creates one sort of opportunity for these parasites to evolve, but there are others: bacteria, which do not reproduce sexually, nevertheless have genes that can kill daughter cells to which they have not been transmitted.

The existence of selfish genetic elements shows that natural selection goes on not only between organisms, but within them. The non-selfish genes, such as those that lose relatives in the beetles killed by Medea, will be selected to neutralise a selfish gene’s effects. Many organisms seem to carry selfish genetic elements whose effects are hidden by other genes; and, more generally, many features of the cellular machinery look as if they might be adaptations to counteract the forces of internal selection.

The way in which mitochondria are inherited, for example, looks as if it might have been an adaptation to deny opportunities for one part of an organism’s genome to turn on another. Mitochondria are cellular structures that power respiration, and are descended from a bacterium that fused with our ancestors about one billion years ago. They divide independently of the rest of the cell and have kept hold of a small chromosome separate from those in the nucleus. In nearly all species, mitochondria pass down only in the female line: our mitochondria are descended from those in our mother’s egg. In mammals, the mitochondria in sperm cells are marked with a protein tag that causes them to be destroyed after fertilisation.

Mixing mitochondria from two individuals in one egg cell would be like planting two strains of grass in one plot: each would be selected to out-compete the other. The strain that divided more quickly would be favoured, even if this harmed the host’s respiratory functions. Studies in yeast have shown that such mutations are common, and that they can spread to the detriment of the cells that carry them. The most plausible explanation for the uniparental inheritance of mitochondria is that the nuclear genomes of the two mates co-operate to reduce the chance that their offspring’s mitochondria will turn selfish.

That evolutionary biologists think in this way owes a good deal to the work of Robert Trivers. In the 1970s, he described and explored the tensions between co-operation and conflict in many biological interactions. The tension between mates, for example: both parties want to reproduce, but because females typically put more of their time and resources into parental care than males, they have more to lose from choosing the wrong mate, and so are expected to be pickier. Or the tension between parents and offspring: parents want their children to survive, of course, but the offspring are selected to demand more than the parents – whose interests are probably best served by withholding resources for other offspring – are selected to give.

In the 1980s, Trivers became interested in the way that genetic conflicts within individuals might influence social behaviour, and in 1992 he was joined by Austin Burt, an evolutionary geneticist at Imperial College. Genes in Conflict has been a long time coming, and it has the feel of a project that got out of hand. It’s full of good things, but offers little help, particularly to non-specialist readers, in knowing what to make of them. ‘The book can profitably be read in almost any order,’ they write. In other words: here it all is, you sort it out. But reading it did help me work out why evolutionary biology is so compelling. It’s because it is to biology what maths is to physics: a set of beautiful and powerful intellectual tools that unify and make sense of the facts, revealing both life’s strangeness and its logic.

Much of Genes in Conflict is a bestiary, illustrating the variety of selfish genetic elements. In one species or another, bits of DNA selected to put one over on other bits have targeted almost every stage in the process of sexual reproduction in almost every conceivable way. The variety of evolutionary kinks that these elements have been selected to exploit can make the head spin. Take the wood lemming. The X chromosome of this rodent comes in two forms, X and X*. When the X* finds itself in an embryo with a Y chromosome, it converts the would-be male lemming into a female. When this X*Y female mates with a male, a quarter of its offspring end up with two Y chromosomes, one each from the mother and the father, and that kills them. Two-thirds of the surviving offspring of an X*Y lemming will carry the X* – which, like Medea, benefits from the reduced competition from siblings – and all will be female.

Sometimes, the whole genome reneges on the genetic contract. In about half of all species of scale insects (a group of aphid-like bugs), females make their male offspring ditch the entire paternal genome. Only the genes inherited from the mother make it into the offspring’s sperm, so that any maternal gene in a son is guaranteed to be present also in a grandchild. Stranger still, we know of three species – a stick insect, a freshwater clam and a cypress tree – that can make sperm with a full genetic complement. When such a sperm fertilises an egg, it ejects the maternal chromosomes, turning that female’s offspring into clones of her mate.

Genes that are favoured by natural selection, but which harm the organisms that carry them, have an obvious appeal to genetic engineers. As far back as the 1970s, biologists were trying to use a killer Y chromosome (one that destroys X-bearing sperm, and so eliminates female offspring) to control the yellow fever mosquito. Now, we can build selfish genetic elements that can spread from one chromosome in a pair to the other. It’s plausible that we might one day design a mosquito carrying an element that inserts itself into a gene essential for survival or disease transmission, and that by releasing a few of these into the population, the species could be controlled or neutralised. Advocates of releasing genetically engineered organisms into the environment may stress how unlikely it is that the gene will spread through wild populations, but the prospect of using genes designed to do just this is sure to alarm anti-GM activists. Anyway creating such an organism is still technically challenging – the scheme to engineer all-male mosquitoes was undermined by the insect’s already having genes that suppress the killer Y – and it seems unlikely that the biotech industry would throw its weight behind making a GM organism needed only in small quantities.

One of the things that I imagine held this book up is the number of things we still don’t know about selfish genetic elements. We don’t know how most of these genes achieve their effects, or how widespread they might be, in terms of which species have which elements and how common elements are within species. We don’t know, either, what their influence is on the genetics and evolution of populations: it’s possible that species might have been made extinct by sex-changing chromosomes such as the mosquito’s killer Y and the lemming’s X*. It might be helpful to think of selfish genetic elements as mini-predators and parasites hunting in the ecosystem of the genome. Most species are rare and narrowly distributed, and most parasites are specialists, exploiting one or a few host species. Likewise, selfish genetic elements are certainly diverse, but I would guess that most of them are found in only a few host species – lemmings will not have a Medea gene, and beetles will not have an X* – and that they will be relatively rare in the species that carry them.

But one class of selfish genetic element has been found in every species so far examined. In the early 1950s, Barbara McClintock was studying the genes that control the colour of maize kernels. Some maize strains have ears that are a mosaic of differently coloured kernels, and in a stable genome the pattern of this mosaic should be inherited faithfully from one generation to the next. But McClintock noticed that kernels sometimes changed colour. After many generations of breeding experiments which allowed her to fix the location of the relevant genes and track their changes, McClintock attributed this inheritance pattern to the movement of genes about the genome. At the time – before the structure of DNA was known – few believed that chromosomes and genetic material could be so fluid, but the development of molecular biology proved McClintock right: she won a Nobel Prize in 1983.

Unlike Medea and its ilk, the mobile genes discovered by McClintock, now called transposable elements, or transposons, show no bias in their inheritance. Instead, they insert copies of themselves at other places in the genome, thus exploiting the most basic fact of natural selection: that it favours any piece of DNA that can get itself copied. Typically, genes do this by endowing their organism with a useful trait, and employ DNA to store information. But this information storage system, the genome, can itself be exploited by anything that can copy its own DNA without going to the bother of making something useful, in the same way that a bit of computer code can spread by hitching itself to something that lots of people want, like Microsoft Office, or something they don’t, like a virus.

This is such a successful strategy that it has evolved many times, in many different forms. Some elements code for a protein that recognises the DNA sequences on either side of the element, cuts it out and reinserts it elsewhere. By timing this manoeuvre so that it takes place during DNA replication, the element gets copied twice, like someone running to the back of the dinner queue for a second helping. Other elements stay where they are, but make a virus-like copy of themselves that reinserts elsewhere in the genome. The human genome contains about four million points where dozens of different types of transposable elements have inserted themselves. Together, they make up half of our DNA. Most of these jumped into place long before humans evolved, and most are fossils that have lost the ability to jump. But some are still active, and cause a small percentage of all new cases of genetic disease, including porphyria and haemophilia, when they insert into the wrong gene. Many biologists have come to think that their ability to cause genetic change has made them important in evolution; it has also made them useful in biotechnology and potentially in gene therapy.

But for most of us, carting all this extra DNA about probably does us neither harm nor good. Most selfish genetic elements, although they might be able to kill cells or individuals that don’t carry them, have little effect on the outward form or inner biology of their hosts. They can’t spread like regular pathogens, so their continued existence depends on the host surviving long enough to reproduce.

There are forms of conflict within the genome, however, which have wider effects. Maternal and paternal genes, for example, differ in their evolutionary interest. This is particularly true when, as for most mammals, mothers are more involved in parental care than fathers, and when females mate with multiple males. A father’s genes want his mate to invest in his offspring, and not in any she might have by another male. Maternal genes, on the other hand, want to protect the female from which they came, so that she can survive to produce more offspring: full or half-siblings that will also carry maternal genes.

But a gene might find itself in a male or a female, so that its interests will differ from one generation to the next. The purpose of a biochemical mechanism called genomic imprinting is to switch genes on or off depending on whether they came from the father or the mother.

In humans, geneticists have found more than a hundred imprinted genes. In those that are paternally imprinted, the copy that came from the father is active, and the one from the mother is silent. These genes tend to promote growth, whereas maternally imprinted genes tend to suppress it. Normal development is the outcome of a balance between maternal and paternal genomes, but sometimes this gets upset. If maternally imprinted genes are silenced, offspring come out much larger than normal. Children with Prader-Willi syndrome, on the other hand, lack a chunk of the paternal genome: they show little interest in suckling, and grow slowly, as if their appetites are being suppressed by the unopposed maternal genome. Around the age of weaning, however, they pick up a voracious appetite, as if the maternal genome is now encouraging the child to fend for itself.

In many species, including humans, parental investment extends long after birth, and animals live in kin groups, so investments besides those between a parent and child come into play. The reach of imprinted genes thus extends into social behaviour and personality. It is on this subject that Trivers and Burt display the most vigour, since it allows them to write, as they put it, ‘unconstrained by any direct facts’. When the two sexes lead different social lives, evolution can operate on imprinted genes. In many mammals, for example, females stay close to their birthplace whereas males tend to disperse. A mother is therefore more likely to have close relatives nearby, and her genes will be selected to favour behaviours that might benefit relatives at her own cost, such as giving an alarm call to warn of predators, or sharing food.

Paternal genes, in contrast, are more likely to be recent arrivals in the group, and will lack nearby relatives. So paternally imprinted genes are selected to bias behaviour away from the group and towards the individual. Mice have paternally imprinted genes that seem to drive females to invest more in their offspring – and so make more copies of paternal genes – and less in other kin. Imprinted genes can also influence an animal’s ability to recognise kin.

In humans, imprinted genes are implicated in a variety of disorders that affect social skills, including autism and schizophrenia. Turner’s syndrome, for example, results from the loss of one of the X chromosomes. Girls suffering from it tend to have normal intelligence, but poor social skills. Those whose sole X chromosome has come from their father, however, are significantly better off in this regard than those who have inherited a maternal X chromosome, so it looks as if the X chromosome carries paternally imprinted genes that contribute to social abilities. If selection for such abilities has been stronger in human females than males, this makes sense, because an X chromosome in a sperm cell is guaranteed to end up in a female, whereas one in an egg could end up in a boy or girl. Why these genes should be switched off at all is a puzzle, and hard to explain as an effect of conflict within the genome, but it may be that if both imprinted genes were switched on they would be harmfully overactive. The fact that all men have inherited an X chromosome from their mothers, and so have inactive versions of these genes, might partly explain why diseases such as autism are more common in males.

This may sound like rampant genetic determinism. I do favour that view of evolution which stresses the power of natural selection to shape individual genes, rather than the view that sees the biology of individuals as more of a compromise between the interests of genes and the limitations imposed by evolutionary history and embryonic development. And I think that the biology of selfish genetic elements is some of the best evidence for such a view. But, while individual genes may be ruthless, the genome and the organism are pulled in all sorts of directions at once, creating a complex and nuanced set of evolutionary forces. The different genes inside an individual have different interests. What’s more, the interests of a gene change from generation to generation, depending on what other genes it finds itself with, and the sex and social circumstances of its host. ‘The unity of the organism is an approximation,’ Burt and Trivers write. The consequences of that approximation for everything from the most basic aspects of cellular biology to (perhaps) the most subtle features of human personality have been profound.