Inbreeding is bad. At least that is the take home message of my variousposts. But biology doesn't have one final answer, it is a serious of approximations which capture part of a given system. My posts on racial hybridization point to this issue. Today in the West we live in an anti-racist age, so the intuitive benefits of hybridization known from agriculture are often tacitly promoted in the discourse, but the reality is more complex. 100 years ago eugenicists set out to prove the inverse because the norms of society demanded it (e.g., Charles Davenport's studies of Jaimaican Mullatoes where he attempted to show that they were less fit than either of their parental populations). The realities are more complex, and the science is nuanced enough that a range of findings can be extracted to fit your agenda. Why is inbreeding bad? The main reason given is the expression of highly deleterious or lethal recessives. Consider that your parents each have 10 loss of function lethal alleles.^1 If they are unrelated their expectation of complementation is nearly 100%. That is, in the enormous sample space of your genome it is unlikely that unrelated individuals would be heterozygous on the same gene so that there was a possibility for umasking the recessive trait, you would almost certainly have a compensatory copy on hand. Offspring would have a 1 out of 2 chance of inheriting a loss of function allele at 20 loci, assuming that there is no intersection between the parents. Now, imagine that you have two siblings, male and female, who wish to mate. I'm sure this appalls you viscerally, but this is a scientific thought experiment, set your feelings aside. On a given locus, X, there is a 50% chance individual a is a heterozygote, and the same for b. These are independent probabilities. There is a 1 out of 4 chance that both individuals are heterozygote on that locus. This is problematic because that implies 1 out of 4 fertilizations are doomed. Now, since the two individuals are siblings...they have a 1 out of 4 chance that they will be heterozygote on any given of 20 deleterious loci. Of course, 3 times out of 4 they will be either homozygous wild type (1 out of 4) or only one individual will be heterozygous (1 out of 2). But, the chance of the couple coming up "clean" across all 20 loci is less than 0.3% if you multiply out the independent probabilities.^2 The take home message is that inbreeding can make masking deleterious alleles really difficult. It might not be as bad for cousins, but there is a reason that very rare recessive diseases tend to be a phenomenon of cousin marriage in much of the world. Inbreeding exposes deleterious recessives, and this is really bad. Or is it? Consider a plant which "selfs." That is, it is hermaphroditic and it fertilizes its own seeds. The offspring will then be a "self cross." The example above in the situation of a "self cross" would lead to the automatic segregation of alleles so that 1/4 in the first generation would be homozygotes for the loss of function, and so very unfit. In the next generation the heterozygotes would again produce 1/4 recessive homozygotes. And so on. In this way, the deleterious genetic load can be purged from the population very quickly. You see, as the frequency of a recessive drops almost all the alleles are "masked" in heterozygote individuals. The chance to expose the alleles to selection occurs in the case of two heterozygotes mating, which in a selfing is assured. So how does this relate to inbreeding? Some have suggested that various human populations might exhibit different genetic loads. For example, the prediction equation for what percentage of Japanese exhibiting particular rare recessive diseases are the offspring of first cousin marriages is somewhat different than for white Americans. Some have argued that this is because generations of cousin marriage in Japan have expunged these alleles from the genetic background. In this way inbreeding is not all bad (species are to some extent by definition inbred nodes on the tree of life). Among world populations it is perhaps in Southern India where we might attempt to find evidence of purging of genetic load: in many communities uncle-niece marriage is encouraged. The coefficient of relatedness in this case is 1/4, the same as between half-siblings. The coefficient of relatedness between first cousins is 1/8. Do I believe in the power of purging genetic load through incest for humans? Not really. There after all other considerations. But, it is something to consider, and part of the overall picture which approximations can sometimes gloss over. I suspect that in humans and most complex organisms mutational meltdown is far more likely, selection may be given a stronger hand in weeding out deleterious alleles which are masked, but to get to this point power stochastic effects already have to be driving the popuation in the direction of extinction. The 50-500 rule applies to humans too. 1 - These numbers are made up. 2 - The fact that siblings have mated and produced offspring in fact should help set a bound as to the extent of lethal deleterious recessives.