Another poor response to ERV evidence for common ancestry by a creationist.

[sfs]

About the paradox?

“What proportion of nonsynonymous changes are neutral and what proportion are deleterious? The fraction that are neutral, fo, can be calculated by comparing the total mutation rate, µt, with the substitution rate, νo = foµt (KIMURA 1983A, KIMURA 1983B). The proportion that are deleterious is 1 - fo. Using this approach, KIMURA 1983Bestimated that 86% of nonsynonymous substitutions are deleterious. A more conservative estimate is obtained by assuming that silent substitutions are entirely neutral and thus reflect the total mutation rate. Then the ratio of nonsynonymous to silent substitutions (Ka/Ks) estimates fo. This will be an underestimate to the extent that silent mutations are deleterious. Data from Ohta indicate that the average = 0.27 among 49 genes in primates (OHTA 1995 ). This suggests that 1.7% of the genome is subject to constraint [= 0.017]. The estimated genomic deleterious mutation rate, U, is thus ∼3 (U = 175 x 0.017), with a minimum value of 1.5 (U = 91 x 0.017) and a maximum value of 4 (U = 238 x 0.017), based on differences in divergence time,”





“The high deleterious mutation rate in humans presents a paradox. If mutations interact multiplicatively, the genetic load associated with such a high U would be intolerable in species with a low rate of reproduction (MULLER 1950 ; WALLACE 1981 ; CROW 1993 ; KONDRASHOV 1995 ; EYRE-WALKER and KEIGHTLEY 1999 ). The reduction in fitness (i.e., the genetic load) due to deleterious mutations with multiplicative effects is given by 1 - e-U (KIMURA and MORUYAMA 1966 ). For U = 3, the average fitness is reduced to 0.05, or put differently, each female would need to produce 40 offspring for 2 to survive and maintain the population at constant size.”

http://www.genetics.org/content/156/1/297.full

Yes, that's the calculation that assumes that all selection is hard. All selection is not hard. So the conclusion does not follow -- which is why the authors go on to mention the possibility of soft selection two sentences later, a fact you somehow failed to mention. They also mention a couple of other effects that would mitigate the genetic load, one of which certainly occurs.

Greater problems are most likely to come to light in higher genome differences between chimps and humans.

This is not what one could term a fact-based statement.

Evolution is only becoming more problematic, I refer to the irreconcilable observed mutation rates against the needed mutation rates that make a monkey into a man.

An incompatibility that has escaped the attention of scientists. (Which reminds me: weren't you going to explain why Haldane's Dilemma applied to neutral mutations? What happened to that explanation?)

What if “U” is even higher?

What if it isn't?

 

[Zaius137]

(sfs)

“Yes, that's the calculation that assumes that all selection is hard. All selection is not hard. So the conclusion does not follow -- which is why the authors go on to mention the possibility of soft selection two sentences later, a fact you somehow failed to mention.”

You don’t’ see that in considering a “U” value that neutral mutations are already factored out? Deleterious mutations are just that, they exact a price in selection or non-selection. They are deleterious… You seem to be claiming that deleterious mutations just sit around waiting for hard selection.

The “U” value, however you look at it dictates that a population must produce enough offspring to overcome the cost of deleterious mutations. If you cannot show me an alternative calculation I will assume you do not have one…

 

[Zaius137]

Dp....

 

[Zaius137]

But what if “U” is lower???

But it is most defiantly higher as I posted earlier. U=4.2… The female must produce 131 offspring just to overcome the deleterious mutations… The calculation stands.

Please concede the point.

 

[sfs]

(sfs)

“Yes, that's the calculation that assumes that all selection is hard. All selection is not hard. So the conclusion does not follow -- which is why the authors go on to mention the possibility of soft selection two sentences later, a fact you somehow failed to mention.”

You don’t’ see that in considering a “U” value that neutral mutations are already factored out?

Yes, I see that. Since soft selection has nothing to do with neutral mutations, I don't know why you ask.

Deleterious mutations are just that, they exact a price in selection or non-selection. They are deleterious… You seem to be claiming that deleterious mutations just sit around waiting for hard selection.

I have no idea what your sentences are supposed to mean, if anything. What I'm claiming is that soft selection (which is real natural selection against real deleterious mutations) does not incur as large a genetic load as hard selection. I'm claiming it because it's true.

The “U” value, however you look at it dictates that a population must produce enough offspring to overcome the cost of deleterious mutations. If you cannot show me an alternative calculation I will assume you do not have one…

There's no single calculation, since soft selection can take various forms. I'll be happy to show you a simulation of a simple model of soft selection and how it compares to hard selection, however.

 

[sfs]

But what if “U” is lower???

But it is most defiantly higher as I posted earlier. U=4.2…

Under assumptions noted in that paper. There is still a considerable range of possible values for U.

The female must produce 131 offspring just to overcome the deleterious mutations… The calculation stands.

Please concede the point.

Why should I concede a point that's wrong? You obviously don't understand the difference between soft selection and hard selection, don't understand why soft selection reduces genetic load, and don't understand why negative epistasis and early developmental mutations (especially mutations that are lethal to gametes) reduce the demands imposed by deleterious mutations on reproductive capacity. The real world is complicated, especially the real world of living things. You can't take an extremely simplistic model of how organisms work, plug in some numbers and assume you've got the right answer. Not if you want to know how the world really works, rather than just find a convenient cudgel to attack science you don't like.

The simple fact is that we do not know how high a deleterious mutation rate humans (or any other species) can tolerate; there are just too many pieces of information missing. Trying to declare victory over evolution on this point comes across as pointless posturing. Did you really think thousands of scientists were so extremely stupid that they wouldn't have noticed the central theory in their field being falsified?

 

[Zaius137]

(sfs)

You know I am only using the peer reviewed papers and putting them together to get the whole picture. I use those calculations because the scientists use those calculations. The conclusion of the following paper said that the findings were “U=4.2”.

http://mbe.oxfordjournals.org/content/27/1/177.full

I give you proper citations and yet all you say is “The real world is complicated”. Well you’re right but all you have is the science to make sense of it. I am not afraid of where the science leads because I ride those sees on a better ship “The Bible”.

Now about Haldane…


“Haldane’s concept worked correctly only under his two as­sumptions: (1) constant population size, and (2) small selection coefficients (s → 0+).”

“Environmental-change, like mutation, is random concern­ing the organism, and therefore is far more harmful than beneficial. For every “neutral or slightly deleterious” muta­tion that converts to “beneficial,” there will be vastly more converted to become more harmful, with these also tending to have a larger effect—for a net effect that is overwhelm­ingly harmful.”

Now about Haldane hypothesis, you were right, it deals with specific selection parameters which were later extended to a wider range of parameters. I brought up Haldane to use ReMine’s paper which really makes more sense mathematically. If you are really interested about that clarification and are not afraid to go there review the following paper. This paper passed peer review but was not accepted for publication.

http://www.creationresearch.org/crsq/articles/43/43_2/cost_substitution.htm


“Trying to declare victory over evolution on this point comes across as pointless posturing. Did you really think thousands of scientists were so extremely stupid that they wouldn't have noticed the central theory in their field being falsified?”

You know I rather be wrong and learn something than to be right and remain ignorant. I never said scientists were “stupid” they only bought into the wrong paradigm.

 

[Naraoia]

There's no single calculation, since soft selection can take various forms. I'll be happy to show you a simulation of a simple model of soft selection and how it compares to hard selection, however.

Yes plz?

 

[Loudmouth]

I give you proper citations and yet all you say is “The real world is complicated”. Well you’re right but all you have is the science to make sense of it. I am not afraid of where the science leads because I ride those sees on a better ship “The Bible”.

Perhaps you could show us how many deleterious mutations each human currently has, and we can work backwards from there. The argument really comes down to how many slightly deleterious mutations that humans can tolerate, and from what I have read no one has any idea what that number currently is.

I brought up Haldane to use ReMine’s paper which really makes more sense mathematically.

Why does it make more sense?

You know I rather be wrong and learn something than to be right and remain ignorant. I never said scientists were “stupid” they only bought into the wrong paradigm.

Why is the paradigm wrong? Please explain.

 

[sfs]

Yes plz?

This is a simple simulation I wrote a few years ago, although I just tidied it up some today. In the model, the maximum population size is fixed at N (usually set to be 10,000), split evenly between males and females. Each breeding pair has on average O offspring (Poisson-distributed) that have a mean of U new deleterious mutations (in an infinite alleles model), plus inherited deleterious alleles from each parent (binomially distributed from each parent, with mean equal to half the parent's load). All mutations have the same selection coefficient, s, and fitness is multiplicative. A maximum of N offspring are randomly chosen for form the next generation, with a probability of surviving given by their fitness; if less than 2 survive, the population is declared extinct.

In the case of hard selection, the fitness is just given by the number of deleterious mutations carried: (1-s)[sup]m[/sup]. For soft selection, the fitness is relative to the fittest individual in the population, which has fitness = 1.0. (As soft selection goes, this is still pretty hard: the introduction of a single fitter individual reduces the fitness of the entire population by the amount he's better than the previous best, which is pretty weird biologically.)

Under hard selection, the population always becomes extinct if the reproductive rate per individual is lower than 1/e[sup]-U[/sup], consistent with Kimura's formula. For example, if U = 4.2, O = 6 offspring/pair and s = 0.01 (i.e. each mutation hurts fitness by 1%), the number of offspring per generation looks like this:

(The mean number of mutations carried by each individual is also plotted, in blue.) The selection coefficient affects how long it takes for the population to collapse, but does not change its fate. Here's the same scenario, but with s = 0.001 (note change in scale on x axis):

Under soft selection, however, the fitness is decreased only by the difference between the mean individual and the best individual in the population, who is also carrying many deleterious mutations. In the same scenario, but under soft selection, the population behaves like this:

Obviously, no real population experiences only soft selection. so this is not a realistic picture. (On the other hand, the ideal genotype that hard selection is measured against is also unreal, and has never existed. Like every other complex organism, humans have evolved while carrying many deleterious alleles, and it's not clear to me what exactly the perfectly fit individual represents in reality.)

The code for the simulation is here, if anyone wants to look at it. It should compile on any unix/linux system that has the gnu c compiler (gcc).

 

[Blayz]

The code for the simulation is here

Excellent, you work at Broad. Please build a browser version of IGV.

Thanks!

Oh, and you might like to drop some empty index.htmls in your web space, prevent people like me from trawling.

 

[Zaius137]

(sfs)

“I have no idea what your sentences are supposed to mean, if anything. What I'm claiming is that soft selection (which is real natural selection against real deleterious mutations) does not incur as large a genetic load as hard selection. I'm claiming it because it's true.”

I tend to believe that “soft selection” is only obscuration and a smoke screen…

“Soft selection is most commonly defined as frequency-dependent selection, or density-dependent selection. But that is not sufficient to reduce Haldane’s Dilemma, much less solve it. The total cost of substitution has an absolute minimum (that occurs when the selection coefficient approaches 0+), and rises as the selection coefficient rises. Haldane’s equations already favored evolution by granting the absolute minimum total cost of substitution – through assuming consistently tiny selection coefficients (approaching 0+). If the selection coefficient varies (as in frequency- or density-dependent selection), then the total cost of substitution cannot possibly go lower than Haldane’s equations, but will surely go higher – making the problem worse than before.”

Haldane's Dilemma - CreationWiki, the encyclopedia of creation science

 

[becon]

Why does creationism always try to use creationism to show that creationism is true?
that's like letting the accused decide if they are guilty or not, total lunacy.

 

[Zaius137]

(sfs)...
Thanks for the graphs.

“In the case of hard selection, the fitness is just given by the number of deleterious mutations carried: (1-s)m. For soft selection, the fitness is relative to the fittest individual in the population, which has fitness = 1.0. (As soft selection goes, this is still pretty hard: the introduction of a single fitter individual reduces the fitness of the entire population by the amount he's better than the previous best, which is pretty weird biologically.)

Under hard selection, the population always becomes extinct if the reproductive rate per individual is lower than 1/e-U, consistent with Kimura's formula. For example, if U = 4.2, O = 6 offspring/pair and s = 0.01 (i.e. each mutation hurts fitness by 1%), the number of offspring per generation looks like this:”

I believe the formula is not 1/e^-u but 2e^u… hope you did not use it in the simulation.

Your population does not just decline it crashes. Yes, I guess you can say this is not close to reality… because it is not.

 

[Loudmouth]

I tend to believe that “soft selection” is only obscuration and a smoke screen…

Judging from your other posts, you believe a lot of crazy stuff. What we are more interested in is what you can DEMONSTRATE.

“Soft selection is most commonly defined as frequency-dependent selection, or density-dependent selection. But that is not sufficient to reduce Haldane’s Dilemma, much less solve it. The total cost of substitution has an absolute minimum (that occurs when the selection coefficient approaches 0+), and rises as the selection coefficient rises. Haldane’s equations already favored evolution by granting the absolute minimum total cost of substitution – through assuming consistently tiny selection coefficients (approaching 0+). If the selection coefficient varies (as in frequency- or density-dependent selection), then the total cost of substitution cannot possibly go lower than Haldane’s equations, but will surely go higher – making the problem worse than before.”

Haldane's Dilemma - CreationWiki, the encyclopedia of creation science

Then I guess we can trade wiki quotes:

Haldane stated at the time of publication "I am quite aware that my conclusions will probably need drastic revision", and subsequent corrected calculations found that the cost disappears. He had made an invalid simplifying assumption which negated his assumption of constant population size, and had also incorrectly assumed that two mutations would take twice as long to reach fixation as one, while sexual recombination means that two can be selected simultaneously so that both reach fixation more quickly. The creationist claim is based on further errors and invalid assumptions.
Haldane's dilemma - Wikipedia, the free encyclopedia
​

 

[Loudmouth]

Your population does not just decline it crashes. Yes, I guess you can say this is not close to reality… because it is not.

I guess you didn't see the last graph where the population does not crash? This is the point where selection eliminates slightly deleterious mutations at the same rate that they are produced.

 

[Zaius137]

(sfs)

Really I am trying to be polite here. Your program has so many issues, besides being off point, which I can not begin to reply kindly. You need to convince me that “soft selection” is a real argument to Haldane.

For your notes birth rate is: 1/e^-u for Asexual reproduction and 2e^u for sexual reproduction.

By the way you could graph this in Excel and circumvent the ancient compiler.

(becon)

Why does creationism always try to use creationism to show that creationism is true?
that's like letting the accused decide if they are guilty or not, total lunacy.

Because evolution ignores there problems and the real lunacy is evolution.

 

[Loudmouth]

Because evolution ignores there problems and the real lunacy is evolution.

Haldane's dilemma has not been a dilemma for quite some time. Haldane used faulty assumptions, such as those highlighted in the wiki quote above.

You need to convince me that “soft selection” is a real argument to Haldane.

It should be blindingly obvious. We can use the hemoglobin C allele as an example:

Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack

This allele is fitter than the hemoglobin S allele (the sickle cell allele) in environments containing malaria. According to Haldane, the majority of people with the hemS allele should die without offspring to make way for the hemC allele. Of course, this isn't true. Both hemS and hemC will continue to spread with hemC spreading at a higher rate.

 

[sfs]

Excellent, you work at Broad. Please build a browser version of IGV.

I don't build browser versions of anything, and the people who do don't pay a lot of attention to me.

Oh, and you might like to drop some empty index.htmls in your web space, prevent people like me from trawling.

Trawl away. I don't think there's anything very interesting there -- old presentations on evolution and faith, various photos that date from before I started using Flickr, other debris. Oh, and a real simulation package, up a couple of directories.

 

[sfs]

(sfs)

“I have no idea what your sentences are supposed to mean, if anything. What I'm claiming is that soft selection (which is real natural selection against real deleterious mutations) does not incur as large a genetic load as hard selection. I'm claiming it because it's true.”

I tend to believe that “soft selection” is only obscuration and a smoke screen…

“Soft selection is most commonly defined as frequency-dependent selection, or density-dependent selection. But that is not sufficient to reduce Haldane’s Dilemma, much less solve it. The total cost of substitution has an absolute minimum (that occurs when the selection coefficient approaches 0+), and rises as the selection coefficient rises. Haldane’s equations already favored evolution by granting the absolute minimum total cost of substitution – through assuming consistently tiny selection coefficients (approaching 0+). If the selection coefficient varies (as in frequency- or density-dependent selection), then the total cost of substitution cannot possibly go lower than Haldane’s equations, but will surely go higher – making the problem worse than before.”

Haldane's Dilemma - CreationWiki, the encyclopedia of creation science

This is wrong on any number of levels. More to the point, it's also irrelevant, since we're discussing the role of soft selection in mutational load due to deleterious mutations, not the cost of substitution due to beneficial mutations.