Uncles & nieces hittin' it to clean out the gene pool

Inbreeding is bad. At least that is the take home message of my various posts. 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.

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I've just been rereading Ridley's "Red Queen" and I'm curious: wouldn't inbreeding also have a major impact on the individuals' immunity to infection and parasitism? Are there any classic cases of inbred populations getting wiped out by infectious disease?

By Corkscrew (not verified) on 01 Sep 2006 #permalink

I've just been rereading Ridley's "Red Queen" and I'm curious: wouldn't inbreeding also have a major impact on the individuals' immunity to infection and parasitism? Are there any classic cases of inbred populations getting wiped out by infectious disease?

1) yes, it is bad

2) many small indigenous groups who came into contact with eurasians would probably count, depending on where you draw the line at "inbred"

I have some related questions...

Selection processes operates on phenotype. Genes that don't don't affect phenotype can't be filtered. Different selection processes apply to different genes in a genome.

Some lifeforms expose and filter lethal alleles during a haploid life stage. Genes affecting only diploid phenotypes wouldn't be filtered at this stage.

Human cells accumulate DNA damage with age. The germline has better DNA repair mechanisms than other cell types but germ cell do accumulate certain types of mutations. The processes of sperm and egg generation, sperm competition, fertilization, implantation, and embryo development could act to filter some harmful mutations.

In many cases a masked bad allele won't be lethal but could still affect fitness. Sperm competition might eliminate many bad alleles. How much of the human genome is being affected by sperm competition? (I don't mean sperm competition between different males attempting to impregnate the same egg.)

Sperm contribute little or none of the mitochondria in the fertilized egg. (The amount depends on the species.) Mitochondria lack many of the nuclear DNA repair mechanisms. How is accumulated mDNA damage filtered from mother to child?

Cheap DNA sequencing applied to cell samples will show how much and what types of filtering are occuring at each stage.

Does anyone know what genes are active during the haploid sperm stage? Are most of the needed mRNA's already present before the final meiosis stage?

afaik, mature sperm a transcriptionally inactive. their DNA is too condensed by protamines to be availble for transcription.

By Rikurzhen (not verified) on 01 Sep 2006 #permalink

Sometimes inbreeding is good. If you mate with a relative, you can increase your inclusive fitness since you are helping to spread identical-by-descent genes (this is because a sister can improve her brother's mating success--and hence her inclusive fitness--by mating with him, independent of the mating opportunities he pursues elsewhere). Fisher pointed this out and Hanna Kokko recently modeled it. I predict that outbreeding depression and its relationship to kin selection will likely become more popular in the human evolution literature.

By Rich Lawler (not verified) on 01 Sep 2006 #permalink

I predict that outbreeding depression and its relationship to kin selection will likely become more popular in the human evolution literature.

if 1st cousin matings were extremely favored one would assume that they would be normative, and not the minority, as we would have evolved a prefered matings to those who are genetically close to us, no? many animals have a not-too-near & not-too-far mating strategy predicated on HLAs. our own species might have this, though i am skeptical it is anything as near as 1/8 coefficient of relatedness, most pre-modern peoples would probably be cousins within the clan, but wife exchange seems to have been the norm.

A not-too-near, not-too-far mating strategy might possibly characterize humans. I'm only saying that when it is discussed there's a lot of theoretical emphasis placed on the former and not the latter. I am only predicting that soon folks may start paying theoretical attention to the latter.

By Rich Lawler (not verified) on 01 Sep 2006 #permalink

I am only predicting that soon folks may start paying theoretical attention to the latter.

prior to the modern era do you find it plausible that selection could ever have shaped a proximate behavioral strategy which would take this into account? the key problem with kin selective narratives of human societies is that by definition small human bands on the order of 12-200 would be bounded by genetically close groups. there maybe a physiological fitness hit for modern outbreeding (i.e., chinese + swedish), but, an aversion could never have evolved because it was never a consideration. whether there was an enviornmental of evolutionary adaptiveness, by definition in premodern situations the spatial horizon of mate choices seems to have been narrow enough that the genetic distance would have been minor.

Thanks Rik.

So sperm competition would only be selecting between different germ cell lines that are producing the sperm. That might provide modest filtering of some types of new mutations but you wouldn't see the significant removal of bad alleles that a haploid life stage provides. Hmmm...that is disappointing.

In nature, there is no good or bad. Inbreeding is bad for the individual, as it increases the chances of having a defectuous child, but good for the community, as it purges nocive recessives. Current wholesale mixing is dysgenic, but this is an untreatable issue in our generation.

Current wholesale mixing is dysgenic, but this is an untreatable issue in our generation

you don't know this. probably depends on the communities in question too. you are simply asserting this, but that's nothing new....

There are some studies of the effects of close inbreeding among South Asians - especially in Tamil Nadu, where uncle-niece marriage is common (dirty old men!) The results, if I recall correctly, are that the fitness effects are significant but not huge. The number of offspring of such marriages may even be above average, for socio-economic reasons. The main researcher is A. H. Bittles.

Do the following four facts have any implications for this post.

Almost all the pet Gerbils in the world are descended from twenty breeding pairs.

All US Starlings are descended from at most 100 birds.

Many Dog breeders swear by the grand-sire grand-dam mating

When marrying within one of the four (I think) large clans as they are supposed to, Koreans pay for careful research the prospective spouse's family tree to make sure they are not related.

In humans the most deleterious conbinations would spontaineously abort while many of the ones that resulted in a baby would presumably not be terribly obvious to a propective mate.

With arranged marriage especially favouring cousins then lack of choice might mean the quantitative reproductive fitness of the person with a mildly deleterious combination of alleles might not be reduced by much. It might even be greater for women with inbreeding depressed IQ.