Pleiotropy and the Neutral Theory of Evolution

Came across this interesting article recently. Wonder how a situation where the entire genome effects every complex trait will effect the neutral theory of evolution.
Perhaps @swamidass can comment if he has the time.

Excerpts from the article which describe the concept are below-

The roots of many traits, from how tall you are to your susceptibility to schizophrenia, are far more tangled. In fact, they may be so complex that almost the entire genome may be involved in some way, an idea formalized in a theory put forward last year.

The authors described what they called the “omnigenic” model of complex traits. Drawing on GWAS analyses of three diseases, they concluded that in the cell types that are relevant to a disease, it appears that not 15, not 100, but essentially all genes contribute to the condition. The authors suggested that for some traits, “multiple” loci could mean more than 100,000.

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Do not use a url as the title. Do not post bare links.

Put relevant title and relevant excerpts. Always.

OK sorry, will correct…

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Is this ok?

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Add some salient excerpts and you are done.

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The important part is the “almost the entire genome”. There are obvious exceptions to the rule (e.g. achondroplasia, hemophilia), but I think they do make the important point that scientists shouldn’t fall into the trap of focusing on variation within one gene. Scientists can lose sight of the larger picture due to the attractiveness of finding the magic genetic bullet.

Their theory is also a bit too vague. They are saying that many traits are influenced by almost the entire genome. That’s enough wiggle room to drive a truck through.

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I’m on board with omnigenics, though I had not previously heard of the term.

It has long seemed to me that what Mendel studied was atypical. It is more realistic to assume a gene affects every trait, and a trait depends in some way on every gene. Life is not just simple combinatorics.


I don’t see how there is much wiggle room to what they are saying. It should be easy to disprove.

The interesting part is that many people who do GWAS actually seem to agree. Besides, it more or less dashes the hope of finding a large no: of genetic cures for ailments. This is a field that involves a lot of money, and people have motivation to find single gene solutions.

Anyway, my main question was what impact does it have on the neutral theory of evolution.

This is an interesting comment. So how do you think this will impact theories of evolution?

Pleiotropy is a well known fact of genetics. It makes it much easier to imagine beneficial mutations, and much harder to find them after the fact. This is consistent with neutral theory, but has some people talking about a revision to “near neutral” theory. Population genetics is unaffected.

I don’t get how it makes it easier to imagine beneficial mutations. Can you explain?

If there is something you want to happen (e.g. deal with Vit C deficiency, or get rid of lactose-intolerance) it is means there are many-many-many more ways to solve that problem. It much more likely that a beneficial mutation will arise. Moreover, multiple mutations with small affects can arise independently and then be sorted together later for a large effect, which can then be even more effectively selected.

We can experimentally validate this in cancer too. We see the same thing there (minus the recombination). There are just many many ways to solve the same phenotypic problem. Pleiotropy is what makes that possible. Aggregating multiple pleiotropic mutations can make a weak affect very strong too. Rather than requiring a specific mutations in specific mutations, you just need one of a large number of possible solutions.

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I was thinking about it the other way. Omnigenics means that most genes effects more than one trait
This makes things relative. A mutation could be beneficial for a trait, neutral for many other traits and deleterious for others all at the same time.
So every mutation that has an impact, would impact many traits leading to complex unpredictable situations.

What solves that is that most the effects are small, and that different mutations will usually have a different profiles. If you then aggregate different mutations with the same small positive effect together, the irrelevant effects average out.

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Could work the other way too right. Mutations with slightly negative effects could aggregate and wipe out the species. Thats more in line with cancer isn’t it.

I think it is already there in our understanding of evolution.

Can you elaborate how this is so?

I’m not a biologist. What I observe is that biologists do assume that there could be many genes involved in particular traits.

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Yes I get that. However, omnigenics would involve more than many genes involved in particular traits. It would demand a systemic approach. Each gene involved in many or all traits… and each trait as a result of interaction of many or all genes.

No it could not work the other way. Bad combination will kill the individual, but not the whole population. It is called negative selection.