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INBREEDING is bad. We seem to know this instinctively. Virtually every human society has some form of incest taboo, and most people find the idea of having sex with a sibling or parent utterly disgusting 鈥� whatever Freudians might say. Even Darwin, who knew nothing about genetics, realised that the offspring of related parents tend to be weak, although that didn鈥檛 stop him marrying his first cousin Emma Wedgwood. And here is the crux: although culture and biology conspire to make close relatives undesirable as sexual partners, nobody really knows how close is too close.

In the past, the effects of inbreeding could only be uncovered by tracing genealogies or, in the case of non-humans, by watching to see which animals mated with which and then studying the offspring of related parents. Not surprisingly, results were scarce.

These days biologists can look for evidence of inbreeding in an individual鈥檚 genes, thanks to advances in genomics. One new technique, pioneered by zoologist Bill Amos from the University of Cambridge, even promises to tell you how closely related your parents were using just a small sample of your genetic material. We are finally starting to see the full extent and effect of inbreeding. And if Amos is to be believed, the situation is much more worrying than anybody suspected.

Using his new technique to study wild animals, Amos has found that inbreeding could be more important in determining an individual鈥檚 chances of survival than random factors such as environmental change. What鈥檚 more, he argues that the adverse effects of inbreeding are not restricted to the offspring of brother-sister and parent-child matings, but span the entire spectrum of relatedness. Some biologists think that Amos鈥檚 claims are overblown. Others argue that we still don鈥檛 know enough about the genomes of most animals to use genetic markers as a reliable indicator of inbreeding. But if Amos is correct then the implications are far-reaching. We should change the way we try to protect endangered species and stop wasting time trying to rehabilitate sick animals who will only fall ill again. We might even have to think about human disease in a different way. There is a lot at stake here 鈥� not least Amos鈥檚 reputation.

Ten years ago, conservation biologists didn鈥檛 rate inbreeding as a problem for wild animals. Captive breeding of related individuals was known to damage the prospects of their offspring, but in nature such effects were thought to be insignificant compared with more immediate risks like starving, not finding a mate, or being shot. 鈥淚n the early 90s, people were saying 鈥榠nbreeding effects are trivial and don鈥檛 matter in the wild鈥�,鈥� recalls Lukas Keller who has recently moved to the University of Zurich in Switzerland. 鈥淏ut no one had actually measured them.鈥� That is because working out family trees for wild populations is phenomenally difficult. Zookeepers and breeders know exactly how much inbreeding there is because they choose which animals will mate, but identifying the parents and grandparents of animals in their natural environment is quite another matter. 鈥淧edigrees for wild populations are very rare,鈥� says Keller.

He knew that if he wanted to find out about inbreeding in the wild he would have to pick his subject carefully. So he began working on a small population of song sparrows on Mandarte Island, off Vancouver, that had been intensively studied since 1975. The island is so tiny and sparsely vegetated that every single bird can be monitored. Each chick is ringed, and matings are observed, making it possible to calculate exactly how inbred each individual is. What Keller discovered was that when severe winter storms caused a population crash on the island 鈥� killing more than 90 per cent of the population 鈥� the inbred individuals perished. All birds from matings between first cousins or closer were lost.

Keller鈥檚 study, published in 1994, made people sit up and take notice. Inbreeding suddenly seemed more malevolent than they had expected. Since then, around 50 studies have revealed 鈥渋nbreeding depression鈥� in all kinds of species, from woodpeckers to wallabies. For example, Loeske Kruuk from the University of Edinburgh, UK, and colleagues found that when collared flycatchers breed with nest mates their offspring are 94 per cent less likely to make it to maturity than normal flycatcher chicks. And a study of the African butterfly Bicyclus anynana, by Ilkka Hanski from the University of Helsinki, Finland, reveals that half the male offspring of sibling couplings are sterile.

鈥淥ver the last few years, we have seen more and more data from individual-based studies, and we now know that inbreeding depression is quite common in wild populations,鈥� says Josephine Pemberton, a geneticist from the University of Edinburgh. But charting the sexual comings and goings of wild animals is painstaking work at best, and totally unfeasible at worst. 鈥淚t would take 300 years to develop a pedigree for elephants,鈥� Keller says. It is only with the advent of genomics that biologists have started to get the wider picture.

Aside from genes on the sex chromosomes, everyone inherits two copies of each of their genes, one from their mother and one from their father. Usually the two copies are slightly different, and the individual is said to be heterozygous for that gene. But if mother and father are themselves brother and sister, they are likely to have inherited the same copies of genes from their parents, so their offspring will inherit many identical pairs of genes 鈥� they will be highly homozygous. It is this lack of genetic variability that can be the undoing of inbred individuals, because mutated genes will inevitably be expressed. Heterozygosity, by contrast, means mutated genes can be masked by healthy versions of the gene.

A special type of genetic marker known as a microsatellite has made it possible to measure an individual鈥檚 level of homozygosity, giving a broad estimate of the degree of inbreeding. Microsatellites are stretches of non-coding DNA containing many repeats of a short sequence of the chemical bases that make up the code, like a stutter. It may be just a pair of bases repeated a hundred times, for example. Although they are not genes, they are ideal for investigating inbreeding because the number of repeats is highly variable, and individuals often have two versions of different lengths inherited from their parents. What鈥檚 more, microsatellites are relatively easy to locate and isolate from the rest of the genome.

The technique is still very new, but in the past five years a handful of studies have demonstrated the dangers of inbreeding in wild populations by showing that animals with more homozygous microsatellites fare worse than highly heterozygous individuals. One such study was done by Dave Coltman from the University of Sheffield, UK, who looked at the wild Soay sheep that eke out an existence on a few remote islands around the UK.

鈥淚ndividuals who were less heterozygous carried more parasitic worms,鈥� Coltman says. In other words, they were more likely to be sick.

But looking for homozygosity is a crude measure of inbreeding. 鈥淚t just asks whether the two genes you inherited from your mother and your father are the same or different,鈥� Amos says. This only tells you very roughly how inbred an individual is. That鈥檚 because some stretches of DNA are naturally more heterozygous than others, and without knowing which is which you can鈥檛 tell precisely how related an individual鈥檚 parents are.

Amos鈥檚 approach is more sophisticated. He considers each microsatellite separately, taking its identity into account, and weighting the significance of homozygosity according to how common that form of microsatellite is in the population. Such information is already used to estimate how related two individuals are to each other based on what genes they share. Amos illustrates the point with an example: 鈥淚f you saw two albinos at a bus stop, you might assume they were related, because albinism is rare. The chances of seeing two unrelated albinos together are small.

鈥淢y contribution was to spot that you could do this using the two genes in a single individual, to measure how related the mother and father were,鈥� he says. If an individual has two identical copies of a gene, it doesn鈥檛 necessarily mean they arrived from related parents. But if hardly anyone else carries those genes, it is very likely to mean that. An individual with unrelated parents will only have as many identical pairs of genes as you would expect by chance, given the frequency of the different genes in the population.

Amos鈥檚 calculation gives each individual a score called the internal relatedness index, based on about 10 different microsatellites. If the parents are unrelated, the score is 0. Scores around 0.25 indicate they are half siblings, and up to about 0.5 indicates full siblings. 鈥淭his method has much greater resolution than heterozygosity,鈥� Amos says. 鈥淲e can distinguish between inbreeding at the level of fourth, fifth and sixth cousins.鈥� At such levels the ill-effects are likely to be subtle. 鈥淲e are not looking for village idiots here,鈥� he says.

Relative disadvantages

While most work on the effects of inbreeding has looked at small, isolated or endangered populations that are highly inbred, the species in Amos鈥檚 studies are not particularly endangered or inbred. His findings suggest that the disadvantages of inbreeding are more pervasive than anyone had suspected. In albatrosses, pilot whales and grey seals, for example, animals with higher internal relatedness scores produce fewer young. 鈥淲e are finding very strong effects wherever we look. We suspect inbreeding might explain a surprisingly high proportion of fitness in all species,鈥� he says.

That view is reinforced by work published earlier this year by Amos鈥檚 student Karina Acevedo-Whitehouse. She calculated the internal relatedness scores of stranded Californian sea lions at a marine mammal rehabilitation centre. The results were astonishing. Sea lions suffering from disease were inbred, whereas those that had been stranded due to accidental injury, such as being hit by a boat, were not. The most inbred group of all were those that had cancer. 鈥淎mongst cancerous sea lions, the average relatedness index was 0.3, suggesting brother-sister matings,鈥� Amos says. Again, inbred individuals are more likely to get sick.

鈥淚n nature, inbred individuals would just die,鈥� Coltman says. But this may be no bad thing, he points out, because their death removes harmful mutations from the population. 鈥淚f we treated our Soay sheep against worms, more inbred individuals would survive, and so more of the bad mutations would be kept in the population,鈥� he says.

The findings of Amos and his colleagues have stark implications for conservation and wildlife genetics. For a start, rehabilitating sick animals is pointless if these individuals are genetically weak and will fall ill again. Instead conservationists should focus on trying to prevent inbreeding of endangered species by keeping populations as large and genetically diverse as possible, and by encouraging outbreeding between populations. This would mean putting more money and effort into projects such as creating wildlife corridors to link isolated populations, and captive breeding and release programmes to enhance the genetic diversity of small populations.

The idea of closing rehabilitation centres is sure to ruffle some feathers, but Amos鈥檚 research is also stirring up the theorists.

While most experts agree that the offspring of closely related individuals are at a disadvantage, many question his claim that inbreeding effects may be as important as factors such as environmental challenges in determining an animal鈥檚 chances of survival. 鈥淭he effects of inbreeding on the chances of a red deer surviving its first year of life are substantially smaller than the effects of something like the weather,鈥� says Tim Coulson from the University of Cambridge, who studies the deer on the Scottish island of Rhum. Others are not convinced that inbreeding depression extends to the offspring of distantly related parents.

More fundamentally, some researchers have raised doubts over the validity of genetic markers as indicators of inbreeding. In a recent study, Jon Slate from the University of Sheffield, looked at the microsatellites of animals with known pedigrees from 10 different species, including New Zealand sheep. 鈥淚n most cases, heterozygosity was a very poor predictor of inbreeding,鈥� Slate says. He argues that since Amos鈥檚 internal relatedness index produces similar values to simple heterozygosity in most populations, his measure of inbreeding is also flawed.

But nobody doubts that genes tell the story of our genealogy, so what is the problem? 鈥淭his is a sampling issue,鈥� Coulson says. 鈥淚nbreeding is a genome-wide process, occurring over thousands and thousands of genes. How can you be sure that your sample of 10 markers represents the same effect?鈥� Most studies, including Amos鈥檚, use 10 or 11 markers. Slate, working with Patrice David from France鈥檚 National Scientific Research Centre in Montpellier, created a mathematical model to estimate how many markers are needed to reliably indicate the degree of inbreeding. 鈥淵ou need more than 100 different markers,鈥� he reports. 鈥淎nd there aren鈥檛 that many available for most species.鈥�

If genetic markers do not reflect inbreeding, why is there a relationship between heterozygosity and reproductive success, or sickness, Amos counters. But Slate says it鈥檚 not that simple: 鈥淚f one of the markers is closely linked to a beneficial gene, or a deleterious gene, then an overall association can arise in the absence of inbreeding depression. You can test for this, by removing each marker individually, but Amos and his team did not.鈥�

Amos is unswayed. 鈥淭hese arguments have difficulty explaining how birth weight, juvenile survival, parasite load, susceptibility to cancer, and reproductive success all show effect in different species with randomly selected microsatellites,鈥� he says. 鈥淭he microsatellites cannot all be located near genes that are independently important.鈥�

Undeterred by his critics, Amos is convinced he is onto something. 鈥淲e鈥檙e sitting on a goldmine here,鈥� he says. His enthusiasm is shared by his colleagues who are excitedly looking for inbreeding effects in genetic samples from all kinds of species, including humans. 鈥淚nbreeding depression decreases when a population expands, and increases if it shrinks,鈥� Amos says. In the developed world human populations are shrinking after a phase of massive expansion, so we are likely to start seeing more inbreeding depression. Amos suspects this might explain a recent finding that people suffering from tuberculosis tend to have lower than average heterozygosity. And he believes other modern epidemics might turn out to be connected with inbreeding.

If Amos is correct then inbreeding is not just a worry for conservationists and animals breeders. 鈥淭he less related your parents were, the better you do, across the board,鈥� Amos says. So, while you are unlikely to be the progeny of incest, you might be operating under a genetic disadvantage simply because your parents came from the same town.