That’s a reason for it to stop being selected against. For it to actively spread as is being claimed above, it’s got to be contributing something, or very very lucky.
That’s a reason for it to stop being selected against. For it to actively spread as is being claimed above, it’s got to be contributing something, or very very lucky.
Suppose you have two types, A and B, and each type gives birth to itself with fidelity .999. (That is, out of a thousand births from As, you have 999 As and 1 B, and the same but reversed for Bs.) As have 1 child each on average; Bs have .5 children each on average. There is a equilibrium ratio of As to Bs in the population that you can figure out pretty easily.
Now suppose the number of children the Bs have raises up to .9. What happens to the ratio of As to Bs?
The selection pressure is still in favor of As, but even when it’s strong Bs are still around because of the mutations. (With sexual selection, and multiple genes, it becomes easier for B contributors to stick around in the gene pool.) When you decrease the edge that As have over Bs, the equilibrium number of Bs increases.
Sure, it’s a toy example without sex. Even so, if the mutation rate were one in a million instead of one in a thousand, you would still have a equilibrium ratio of As to Bs. When you add in sex and precursor genes (that is, you don’t have schizophrenia unless you have two copies of an allele, or you need multiple different alleles, etc.) then the selective pressure depends on the prevalence- as the condition gets rare, the selection pressure on the precursors lowers because potential mates are unlikely to have the other half necessary to get the condition. (This gives you another equilibrium ratio of the number of people with the condition.)
The real incidence of schizophrenia is about one in two hundred. That suggests there’s something going on beyond mutation- either some of the schizophrenia precursors are positive, or it’s caused by a virus, or genes just determine susceptibility, or the heredity has to do with prenatal environments, or so on. (With inclusive ’or’s.)
Sure, those are all possibilities. But there are other possibilities also. For example, it could be that the selection pressure was really only high fairly recently. Most people who get schzophrenia get it sometime between around 15 to 35 years of age, and for a large fraction the symptoms come and go. So in many classical societies they would have had time to reproduce. Moreover, in some societies people with symptoms became things like shamans. So the selection pressure would likely have been not nearly as negative in the past, possibly to the point where neutral drift could account for a decent fraction of the alleles.
All of that said, I agree that it is likely that some of the alleles which produce a likelyhood of schizophrenia at some point had positive selection pressures on them for other reasons. But humans are so far from our ancestral environment that alleles which once had positive selection pressure don’t necessarily have much or any today.
Consider a deck of cards that is randomly shuffled. It must come to some arrangement. Now consider the chance that shufflling another deck gives the same result. That’s only 1 / 52! which is around 10^-67. But if someone said that therefore no deck of cards is ever shuffled they’d be wrong. Similarly, consider a protein with 600 base pairs describing it. The chance that a mutation occurs in that specific protein at any given time is pretty small, the chance that the exact same mutation occurs will be much smaller by roughly two orders of magnitude (assuming just singleton substitution errors).
The key is that mutations occur but repeated mutations don’t generally occur unless there’s something very weird going on like in the case of Huntington’s where there’s a whole family of bad alleles and there’s a biochemical quirk which makes the mutations much more likely.
The key is that mutations occur but repeated mutations don’t generally occur unless there’s something very weird going on like in the case of Huntington’s where there’s a whole family of bad alleles and there’s a biochemical quick which makes the mutations much more likely.
Pardon me if I’m being obtuse, but wouldn’t we expect “a whole family of bad alleles” to be the usual case, since you can break a protein in any number of different ways?
I’ve heard that some fairly high percentage of hemophilia A and B cases are de novo mutations (a quick Google turned up this). I’m sure it’s because hemophilia is pretty lethal and often doesn’t get the chance to be inherited, but it’s another case where mutation rates do seem to matter.
Yes, hemophilia is an example like Huntington’s where there’s a family of alleles. And of course, in that case, the allele is extremely lethal, killing a large fraction of males, and killing any female that is homozygous. So the allele has to stay really rare.
In general though for most proteins it is surprisingly difficult to break them. Most mutations will actually be neutral. They will be neutral either because the mutated codon actually codes for the same allele, or codes for a chemically similar allele, or because it is a section of the protein which provides something like structural support, if it mighta ctually have a phenotypical effect that just doesn’t matter much either way . Many other mutations might have a negative effect but it won’t be the same negative effect or it will be a negligible negative effect.. Moreover, some of the negative effects from mutated proteins aren’t because the protein itself is now broken at what it normally does but because the protein now in addition to what it is supposed to do gums something else up or isn’t as easily broken down or something like that. Those sorts of things also require specific mutations to occur. So in general, it is very rare for a mutation to get repeated.
That’s a reason for it to stop being selected against. For it to actively spread as is being claimed above, it’s got to be contributing something, or very very lucky.
Suppose you have two types, A and B, and each type gives birth to itself with fidelity .999. (That is, out of a thousand births from As, you have 999 As and 1 B, and the same but reversed for Bs.) As have 1 child each on average; Bs have .5 children each on average. There is a equilibrium ratio of As to Bs in the population that you can figure out pretty easily.
Now suppose the number of children the Bs have raises up to .9. What happens to the ratio of As to Bs?
The selection pressure is still in favor of As, but even when it’s strong Bs are still around because of the mutations. (With sexual selection, and multiple genes, it becomes easier for B contributors to stick around in the gene pool.) When you decrease the edge that As have over Bs, the equilibrium number of Bs increases.
That assumes a ridiculously high mutation rate. For the vast majority of alleles the mutation rate isn’t what matters but the selection rate.
Sure, it’s a toy example without sex. Even so, if the mutation rate were one in a million instead of one in a thousand, you would still have a equilibrium ratio of As to Bs. When you add in sex and precursor genes (that is, you don’t have schizophrenia unless you have two copies of an allele, or you need multiple different alleles, etc.) then the selective pressure depends on the prevalence- as the condition gets rare, the selection pressure on the precursors lowers because potential mates are unlikely to have the other half necessary to get the condition. (This gives you another equilibrium ratio of the number of people with the condition.)
The real incidence of schizophrenia is about one in two hundred. That suggests there’s something going on beyond mutation- either some of the schizophrenia precursors are positive, or it’s caused by a virus, or genes just determine susceptibility, or the heredity has to do with prenatal environments, or so on. (With inclusive ’or’s.)
Sure, those are all possibilities. But there are other possibilities also. For example, it could be that the selection pressure was really only high fairly recently. Most people who get schzophrenia get it sometime between around 15 to 35 years of age, and for a large fraction the symptoms come and go. So in many classical societies they would have had time to reproduce. Moreover, in some societies people with symptoms became things like shamans. So the selection pressure would likely have been not nearly as negative in the past, possibly to the point where neutral drift could account for a decent fraction of the alleles.
All of that said, I agree that it is likely that some of the alleles which produce a likelyhood of schizophrenia at some point had positive selection pressures on them for other reasons. But humans are so far from our ancestral environment that alleles which once had positive selection pressure don’t necessarily have much or any today.
In that case why is the allele still around at all?
Consider a deck of cards that is randomly shuffled. It must come to some arrangement. Now consider the chance that shufflling another deck gives the same result. That’s only 1 / 52! which is around 10^-67. But if someone said that therefore no deck of cards is ever shuffled they’d be wrong. Similarly, consider a protein with 600 base pairs describing it. The chance that a mutation occurs in that specific protein at any given time is pretty small, the chance that the exact same mutation occurs will be much smaller by roughly two orders of magnitude (assuming just singleton substitution errors).
The key is that mutations occur but repeated mutations don’t generally occur unless there’s something very weird going on like in the case of Huntington’s where there’s a whole family of bad alleles and there’s a biochemical quirk which makes the mutations much more likely.
Pardon me if I’m being obtuse, but wouldn’t we expect “a whole family of bad alleles” to be the usual case, since you can break a protein in any number of different ways?
I’ve heard that some fairly high percentage of hemophilia A and B cases are de novo mutations (a quick Google turned up this). I’m sure it’s because hemophilia is pretty lethal and often doesn’t get the chance to be inherited, but it’s another case where mutation rates do seem to matter.
Yes, hemophilia is an example like Huntington’s where there’s a family of alleles. And of course, in that case, the allele is extremely lethal, killing a large fraction of males, and killing any female that is homozygous. So the allele has to stay really rare.
In general though for most proteins it is surprisingly difficult to break them. Most mutations will actually be neutral. They will be neutral either because the mutated codon actually codes for the same allele, or codes for a chemically similar allele, or because it is a section of the protein which provides something like structural support, if it mighta ctually have a phenotypical effect that just doesn’t matter much either way . Many other mutations might have a negative effect but it won’t be the same negative effect or it will be a negligible negative effect.. Moreover, some of the negative effects from mutated proteins aren’t because the protein itself is now broken at what it normally does but because the protein now in addition to what it is supposed to do gums something else up or isn’t as easily broken down or something like that. Those sorts of things also require specific mutations to occur. So in general, it is very rare for a mutation to get repeated.
Not necessarily, see Eliezer’s post Evolving to Extinction.