Inbreeding/Assortative Mating and a Decrease in Heterozygosity

[FadedFace]

At the risk of making myself sound silly, I have the following question:

 

I am currently taking evolution in university, and am having trouble grasping a concept. With self-fertilzation, I can understand why there would eventually be a deficiency of heterozygotes (ie: A1A2 self-fert will continually have a chance to add A1A1 and A2A2 offspring to population, along with those A1A1 and A2A2 plants self-fertilizing themselves). For some reason, however, I am having difficulties in envisioning how inbreeding (in animals) actually leads to a deficiency in heterozygosity in a population. I know that it happens through inbreeding and assortative mating, but not WHY. Could someone concisely explain this?

Thank you so much in advance.

[questionposter]

At the risk of making myself sound silly, I have the following question:

 

I am currently taking evolution in university, and am having trouble grasping a concept. With self-fertilzation, I can understand why there would eventually be a deficiency of heterozygotes (ie: A1A2 self-fert will continually have a chance to add A1A1 and A2A2 offspring to population, along with those A1A1 and A2A2 plants self-fertilizing themselves). For some reason, however, I am having difficulties in envisioning how inbreeding (in animals) actually leads to a deficiency in heterozygosity in a population. I know that it happens through inbreeding and assortative mating, but not WHY. Could someone concisely explain this?

 

Thank you so much in advance.

 

It's just that there are certain combinations of genes that code for rare diseases, and those genes were formed by random mutations a long time ago. However, they continued to survive because most often those genes are not in the right combination and aren't active so they often don't lead to the host's death and can be passed on.

Edited February 17, 2012 by questionposter

[Arete]

It's just that there are certain combinations of genes that code for rare diseases

 

This has nothing to do with disease at all - it's a basic pop gen question.

 

A population in HWE is assumed to be panmictic with individuals mating randomly. The reason inbreeding creates a heterozygote defecit is because individuals are mating with other individuals that are more similar to themselves than expected in a randomly mating population and thus violates an assumption of the HWE model. Coefficients of relationship calculations are described here: http://en.wikipedia....of_relationship

 

Inbreeding indviduals are more likely to produce with an individual with which they share common alleles, thus producing more homozyotic offspring than expected under HWE. Increased homozygosity can result in the expression of a higher proportion of recessive alleles and subsequent inbreeding depression of phenotype.

 

Assortative mating is a different issue to inbreeding. Assortative mating implies selection, and populations/genes undergoing selection are generally not in HWE. This is because, again breeding is skewed in either a positive/negative direction for a particular phenotypic trait and thus, individuals displaying/lacking that trait are more or less likely to pass on their genes to the next generation than expected under a randomly mating panmicitc population.

 

Basically, any phenomena that interrupts random mating, be it inbreeding, selection, population substructure etc will cause a population to deviate from HWE. This makes it a good test for selection in either a population or a particular gene

Edited February 17, 2012 by Arete

[Ringer]

I just want to add that just because a population is deviating from the HWE, that doesn't mean it is doing so because of deleterious genes. HWE is violated any time any sort of evolution is occurring, not just when something bad is happening.

[FadedFace]

Thank you so much for the replies. I was thinking along those lines, but for some reason I couldn't adequately piece it together. Now that you explain it nicely in words, it makes it quite obvious how such mating schemes would result in a deficit of heterozygotes...as a matter of fact, the way you put it makes it seem like it should be obvious. Thanks

Edited February 17, 2012 by FadedFace

[Arete]

I just want to add that just because a population is deviating from the HWE, that doesn't mean it is doing so because of deleterious genes. HWE is violated any time any sort of evolution is occurring, not just when something bad is happening.

 

To indulge in even further nitpicking - a population can evolve through stochastic drift without violating HWE, it's under selective evolution models it is violated

[questionposter]

This has nothing to do with disease at all - it's a basic pop gen question.

 

A population in HWE is assumed to be panmictic with individuals mating randomly. The reason inbreeding creates a heterozygote defecit is because individuals are mating with other individuals that are more similar to themselves than expected in a randomly mating population and thus violates an assumption of the HWE model. Coefficients of relationship calculations are described here: http://en.wikipedia....of_relationship

 

Inbreeding indviduals are more likely to produce with an individual with which they share common alleles, thus producing more homozyotic offspring than expected under HWE. Increased homozygosity can result in the expression of a higher proportion of recessive alleles and subsequent inbreeding depression of phenotype.

 

Assortative mating is a different issue to inbreeding. Assortative mating implies selection, and populations/genes undergoing selection are generally not in HWE. This is because, again breeding is skewed in either a positive/negative direction for a particular phenotypic trait and thus, individuals displaying/lacking that trait are more or less likely to pass on their genes to the next generation than expected under a randomly mating panmicitc population.

 

Basically, any phenomena that interrupts random mating, be it inbreeding, selection, population substructure etc will cause a population to deviate from HWE. This makes it a good test for selection in either a population or a particular gene

 

Ok, fine, certain genes paired with each other code for PROCESSES that create rare diseases, and as you so convoluted said, those genes are more likely to be paired with other people who are in the same family because the people in the same family all contain those genes and inbreeding decreases variation that would otherwise dilute any specific gene combination.

But otherwise, what I was saying before about their continuation is correct, because if all those genes were dominant in everyone they appeared in, everyone who had them would have just died off and we wouldn't have that problem right now.

Edited February 18, 2012 by questionposter

[Arete]

Ok, fine, certain genes paired with each other code for PROCESSES that create rare diseases, and as you so convoluted said, those genes are more likely to be paired with other people who are in the same family because the people in the same family all contain those genes and inbreeding decreases variation that would otherwise dilute any specific gene combination.

But otherwise, what I was saying before about their continuation is correct, because if all those genes were dominant in everyone they appeared in, everyone who had them would have just died off and we wouldn't have that problem right now.

 

In the interests of positive criticism - the OP was a relatively simple question (my guess is he/she is taking a 100 level genetics class) about Hardy-Weinberg Equilibrium and it went straight over your head. It might serve you and the rest of the forum well to do a touch more research and a little less posting when it's clear you're unsure of the answer. I would suggest starting here: http://en.wikipedia.org/wiki/Hardy%E2%80%93Weinberg_principle#Deviations_from_Hardy.E2.80.93Weinberg_equilibrium

[questionposter]

In the interests of positive criticism - the OP was a relatively simple question (my guess is he/she is taking a 100 level genetics class) about Hardy-Weinberg Equilibrium and it went straight over your head. It might serve you and the rest of the forum well to do a touch more research and a little less posting when it's clear you're unsure of the answer. I would suggest starting here: http://en.wikipedia....erg_equilibrium

 

He was basically asking if the principal works if things inbreed and cause mutation since they keep the gene pool similar since it assumes no mutation right? Isn't the principal wrong on some levels and may only be used as an approximation in short time spans? So couldn't genetic diseases prove that the principal doesn't always follow through?

Edited February 18, 2012 by questionposter

[Arete]

No. They were asking why inbreeding causes a deficit of heterozygosity relative to expectations under HWE. Read the wikipedia link for an explanation of what HWE is.

 

For the record, inbreeding does not cause mutations.

[questionposter]

No. They were asking why inbreeding causes a deficit of heterozygosity relative to expectations under HWE. Read the wikipedia link for an explanation of what HWE is.

 

For the record, inbreeding does not cause mutations.

 

Hmm, I didn't say inbreeding causes mutations but rather that it increases the likelihood of the same genes that code for genetic diseases being paired with each other, but otherwise is the HWE thing not when the frequencies of alleles change from one generation to the next? Wouldn't it not eventually come to a complete equilibrium? I can't imagine that it would work so perfectly that every single allele or coefficient would eventually have the same exact amount.

Edited February 19, 2012 by questionposter

[Arete]

Hmm, I didn't say inbreeding causes mutations

 

Hmmm

 

if things inbreed and cause mutation

 

 

is the HWE thing not when the frequencies of alleles change from one generation to the next?

 

No. HWE is calculated within a population at a single temporal point. If allele frequencies change from one generation to the next, so does HWE. A population will only progress towards HWE if the assumption of random panmictic mating are met. If non-random mating persists, the population will not be in HWE.

 

This would and a lot of the other questions you have are answered in the first paragraph of the wiki article - it be immensely easier to discuss if you read it.

[Ringer]

To indulge in even further nitpicking - a population can evolve through stochastic drift without violating HWE, it's under selective evolution models it is violated

 

Apologies if my memory is faulty, but I thought the main principle of the HWE is that a population will have a constant allele frequency throughout generations unless acted upon through selection, drift, etc. Since at least one of these things are involved in virtually every population the equilibrium can never be kept. But, I guess that even though that principle is violated the allele frequency can stay constant, though I'm unsure as to how since I am not all that experienced in this area.

[Arete]

Apologies if my memory is faulty, but I thought the main principle of the HWE is that a population will have a constant allele frequency throughout generations unless acted upon through selection, drift, etc. Since at least one of these things are involved in virtually every population the equilibrium can never be kept. But, I guess that even though that principle is violated the allele frequency can stay constant, though I'm unsure as to how since I am not all that experienced in this area.

 

The frequency of certain alleles in a population can change over time due to stochastic random mutation in the absence of selection, and thus the population can evolve over time without alteration to heterozygote/homozygote ratios.

[CharonY]

Normally, the HWE calls for static allele frequencies (often used as a null). Drift and non-random mating even in absence of mutation or selective pressures would violate that. There are (IIRC) certain modifications of testing for HWE that try only to elucidate the effect of fitness influences. In these cases drift and other stochastic events are somehow taken out of the equation. But in the classic sense I am with Ringer, drift violates HWE. Originally drift was possibly not mentioned, however it was implicit in assuming very large populations (which minimize stochastic influences).

[Arete]

The scenario I am evisioning would be as follows:

 

I sample the same locus, from the same population at three different time points. At each time point, allele frequencies are found to be in HWE proportions. However, when I examine haplotypic diversity, I find that the observed haplotypes differ across temporal sampling. The reason I would be able to infer that genetic change over time was likely to be due to stochastic drift rather than selection is due to the fact that haplotypic change occurred without the population deviating from HWE.

Edited February 22, 2012 by Arete

[CharonY]

I see what you mean, and this is also what I meant earlier (though admittedly badly worded, also note that this is not really my field so I may be remembering things inaccurately). Depending on how you test for HWE you can infer different mechanisms for violation thereof. E.g. if you only tested the haplotype frequencies, you would have found that they are not in HWE (I faintly recall some odd methods using Fisher test to ascertain that, although I assume that there must be some kind of regression analyses, or some even more simple models which I simply am not familiar with).

Also statistically, not refuting HWE does not automatically mean that the given allele is in HWE (as you cannot accept the null, although sometimes it is done so in literature). And of course (but that is implicitly stated in your example) a given allele may be found in HWE but it may not hold on the population level (i.e. considering the whole genome pool).

Edited February 23, 2012 by CharonY

[Arete]

I see what you mean, and this is also what I meant earlier (though admittedly badly worded, also note that this is not really my field so I may be remembering things inaccurately). Depending on how you test for HWE you can infer different mechanisms for violation thereof. E.g. if you only tested the haplotype frequencies, you would have found that they are not in HWE (I faintly recall some odd methods using Fisher test to ascertain that, although I assume that there must be some kind of regression analyses, or some even more simple models which I simply am not familiar with).

 

There's three tests you can use with Genepop - one's a 'U test', one an 'exact' test and the third an MCMC based test: http://genepop.curtin.edu.au/Option1.html There's more in Arlequin, DNAsp and I'm sure other software. I have to admit I've always been more interested in the interpretation that the underlying algorithm Once deviation is detected, further analysis can tell you in which direction your population/s are headed and what's likely to be the cause: In my above hypothetical, if you tested a pooled sample from all time periods, it would likely be out of HWE. If you tested again with the samples separated temporally and found them not significantly out of HWE you'd instantly be able to infer that there was genetic structure/turnover over time

 

Also statistically, not refuting HWE does not automatically mean that the given allele is in HWE (as you cannot accept the null, although sometimes it is done so in literature). And of course (but that is implicitly stated in your example) a given allele may be found in HWE but it may not hold on the population level (i.e. considering the whole genome pool).

 

Totally. A test for HWE can only tell you if the allele frequencies are significantly different from what would be expected under a HWE model, and in reality no natural population is actually in perfect HWE. Any empirical study is rather by definition, relative.

[CharonY]

Yupp, makes sense. I assume the initial disagreement was due to the the shifts in perspective.