Deleterious alleles

[ARWallace]

Frank brought up an interesting question a while ago regarding deleterious alleles (such as sickle cell) and whether they might be advantageous in some circumstances. Certainly evolution and population genetics would need to offer some explanation as to why alleles such as these - with obvious selective disadvantages - exist in comparatively high frequencies in some populations. We discussed the relative advantages of heterozygosity in sickle cell, and how this provides some resistance to malaria. I looked around a little for other possible diseases that might have similar advantages in some circumstances, and I came up with a partial list I thought I would share. This may not be a topic of considerable discussion - or even interest - but I thought minimally Frank might be interested...so here's what I found:

1. People with Huntington's Disease tend to have higher fertility and greater resistance to cancer (perhaps because of elevated levels of p53 proteins) than those without it. Given that this disease tends to manifest in the 40's or 50's, this may incur real and tangible benefits to those with the disease in an evolutionary sense.

2. Heterozygous forms of phenylketonuria (PKU) seem to provide some resistance to a fungal toxin (ochratoxin A) which causes spontaneous abortions. Carriers of PKU are common in Ireland and western Scotland, and it appears that the benefits of the carrier form caused this allele in terms of birth rates caused it to become fairly common in these populations.

3. There is a possible heterozygote advantage to carriers of CF who produce small amounts of the abnormal CFTR protein which closes chloride channels in the digestive system (among other places). Small amounts of this protein seem to confer a benefit when exposed to cholera which causes these channels to open resulting in diarrhea (which ultimately kills from dehydration).

4. There are several hypotheses regarding possible benefits to people with Tay-Sach's disease including some claims that it may have conferred a survival benefit when exposed to tuberculosis. But some studies suggest this may not be the case, and that relatively high frequencies of this allele in some populations may be the result of the Founder Effect and genetic drift.

5. A balanced polymorphism exists in the sex-linked disease; Glucose-6-Phosphate Dehydrogenase Deficiency. The enzyme deficiency causes hemolytic anemia which is life threatening. But hemizygous males and homozygous recessive females have some resistance to malaria, so this allele is relatively common (like sickle cell) in areas where malaria is endemic.

So, a few possible diseases which may have benefits in some cases and some situations — much like sickle cell heterozygotes experience in areas of malaria endemicity.

[zoegirl]

Nice list, thanks AR

I'm thinking on this, so might respond later, but need to ponder...knew about the sickle cell, but the others are new to me.

[frankbaginski]

ARWalace,

Thanks for the data. Makes me wonder if by having these conditions it may serve as a bridge to a much bigger positive change in the future. One of the problems with assumed changes is that it is hard to see all small changes as beneficial. If these changes did not stop births but shortened the life span it may be a bridge. So a small step backward could become a giant leap forward. Is there any way to find some old DNA of humans/anything and study these changes with a bridge in mind. From an evo point of view it may be too short but from my adaptation point of view there may be enough time.

Sometimes in math we get stuck so we may change the equations, like polar to cyl and back. Maybe DNA is doing the same thing. It hits a road block that mutation alone can't cross and then steps back and goes around the problem another way. This bridge may not be visable in the end product so trying to figure it out may be impossible. But if you had enough historical DNA you might find a hint of one. Not quite punctuated equilibrium but close. Another way of looking at this is the mutation buys time for the environment to change again so the species continues until the mutation is not needed any longer. So the species with the best adaptation wins out long term even with a short term loss. Now this goes against the report showing the Human DNA filled with problems and at the verge of collapse but it may mean something completely different. Maybe the gathering of defects is exactly what chaos requires. If we all had perfect DNA then a new bug would destroy us. Just a thought.

I think the adaptation of the DNA is much faster than assumed with current models.