Comment on The End of “Junk DNA”? by Sean Pitman.

@pauluc:

I am sorry but my prose seems to have allowed you to parse my comments but miss the intent. In response to your suggestion that we are devolving and accumulating mutations at a dangerously high rate and that we are in eminent danger of genetic meltdown I simply asked you to factor in paternal age as a mitigating factor in allaying your concerns. I made no comment on the veracity of the Bible’s claims of paternal longevity other than to point to similarity in paternal age to that in the existing Sumarian book of the kings. I still do not see that your argument that the yearly mutation rate is the same whether the generation time is 29.7 or 800 years has any value for the person who may have gained 1600 mutations and has high risk of autism as the original research suggested, but that is beside the point.

I’m sorry, but it seemed to me like you presented this argument to question the ability of humans to actually live and reproduce for almost 1000 years. What you still don’t seem to understand is that it isn’t the per generation mutation rate that matters as far as the gene pool is concerned or even the number of detrimental mutations for the offspring born in a given year (compared to some reference point in time). It is the yearly mutation rate that matters when it comes to the gene pool as a whole and the risk for new offspring. This yearly rate stays the same regardless of the generation time. A child born at any given point in time has the same risk of inheriting detrimental mutations regardless of if his father had lived 800+ years or if he/she was born after 800+ years worth of paternal generations. The detrimental mutation load would be essentially the same. I’m really not sure why you’re having such difficulty with this concept?

Also, autism and other genetically-based diseases would not have been as significant a risk when mankind was fresh from the Creator’s hand. Deleterious mutations had not built up to their current levels and associated genetic-based disease risks. Again, such genetic-based diseases will only get more and more prominent as our collective gene pool continues to degenerate over time.

“You also claimed that other forms of mutations besides SNP-type mutations are too high to be consistent with the Biblical model. You were wrong.”

I see your model as based on selective biblical literalism if not inerrancy which to me is incomprehensible outside multiple continuing divine interventions to make the world the way it is. I am happy to concede you are Christian and Adventist though you do not believe the same as me on some points. To me issues of mutation rate are orthagonal to my Christian belief which is based on following Christ as the incarnation of the God of Grace.

Again, the Biblical authors who wrote Genesis clearly intended to be taken literally – to be describing real historical events. The question is, were they right or wrong in their testable statements regarding empirical reality? If they were wrong, the credibility of the metaphysical statements of the Bible also declines – to include claims regarding the life, death, and very nature of Jesus Christ (especially given that He personally confirmed the historicity of the Genesis account of origins).

So, what about your challenges to the credibility of the Bible’s claims regarding historical times and events? You’ve thrown out a multitude of arguments that supposedly falsify the Biblical narrative of history. The problem, of course, is that your claims are the ones that have turned out to be false. The hypothesis that the Bible’s claims regarding origins is empirically tenable remains intact and more vindicated in modern times than ever before. Why then do you try so valiantly to undermine the empirical basis for faith in the credibility of the Bible? Why do you even think Jesus existed and acted in the manner described in the Bible at all if you yourself pick and choose what you will and will not believe? How is this different than wishful thinking?

“And, your claim that deleterious mutations can be effectively removed from slowly reproducing gene pools (via some form of genetic recombination?) is also clearly mistaken.” – Sean Pitman

Beyond process of natural selection I do not know how deleterious mutations might be removed from the gene pool but I am intrigued that long lived animals have lower rates of mutation. Sexual reproduction diploidy is clearly important but I do not at all imagine that we know all about the rate of removal of deleterious mutations despite your modelling assuming we do. What I am not convinced of is that you are correct that death is the only mechanisms of removal and that your conclusion that we are on track for genetic meltdown, subject as it is to huge pressure for confirmational bias from your assumption of devolution, is correct.

Natural selection does not work without the premature death of individuals within a population. And, genetic recombination doesn’t solve this problem (as discussed below).

Also, long-lived animals do not have significantly lower rates of gene pool mutation compared to humans – even with regard to animals demonstrating negligible senescence. In other words, the overall yearly mutation rate for the gene pool as a whole is not significantly different among all types of long-lived animals.

As far as sexual vs. asexual reproduction is concerned, the problem remains even for sexually reproducing species. This is because genetic recombination during meiosis is a random process that does not preferentially select to remove detrimental mutations vs. beneficial or neutral mutations. The only advantage genetic recombination provides is a statistical chance that a percentage of the offspring will have less detrimental mutations compared to their peers. In other words, when it comes to sexually reproducing populations, the ability for genetic recombination during the formation of gametes makes it possible to concentrate both good and bad mutations.

For example, let’s say we have two individuals, each with 2 detrimental mutations. Given sexual recombination between these two individuals, there is a decent chance that some of their offspring (1 chance in 32) will not have any inherited detrimental mutations. But what happens when the rate of additional detrimental mutations is quite high – higher than 3?

To look into this just a bit more, consider another example of a steady state population of 5,000 individuals each starting out with 7 detrimental mutations and an average detrimental mutation rate of 3 per individual per generation. Given a reproductive rate of 4 offspring per each one of the 2,500 couples (10,000 offspring), in one generation, how many offspring will have the same or fewer detrimental mutations than the parent generation?

Inherited…….After Ud = 3
7……………901
6……………631
5……………378
4……………189
3……………76
2……………23
1……………5
0……………0.45
< or = 7……..2202

This Poisson approximation shows that out of 10,000 offspring, only 2,202 of them would have the same or less than the original number of detrimental mutations of the parent population. This leaves 7,798 with more detrimental mutations than the parent population. Of course, in order to maintain a steady state population of 5,000, natural selection must cull out 5,000 of these 10,000 offspring before they are able to reproduce. Given a preference, those with more detrimental mutations will be less fit by a certain degree and will be removed from the population before those that are more fit (less detrimental mutations). Given strong selection pressure, the second generation might be made up of ~2,200 more fit individuals and only ~2,800 less fit individuals with the overall average showing a decline as compared with the original parent generation. If selection pressure is strong, so that the majority of those with more than 7 detrimental mutations are removed from the population, the next generation will only have about 1,100 mating couples as compared to 2,500 in the original generation. With a reproductive rate of 4 per couple, only 4,400 offspring will be produced as compared to 10,000 originally. In order to keep up with this loss, the reproductive rate must be increased or the population will head toward extinction. In fact, given a detrimental mutation rate of Ud = 3 in a sexually reproducing population, the average number of offspring needed to keep up would be around 40 per breeding couple (2 * 1 / e^-Ud) – for two to survive without an increase in detrimental mutations. Humans simply don't reproduce that fast and cannot tolerate a 95% death rate per generation.

Even within mainstream literature clear limitations to mutation rates are known because of this particular problem. Even rapidly reproducing bacteria and viruses have a fairly small limit to the number of mutations that can be sustained per generation. Based on research coming out of Harvard University, that number is less than 6 mutations per individual per generation – for bacteria and viruses as well as most other living things! This is a total number of mutations affecting functional regions of DNA – counting detrimental, beneficial, and neutral varieties.

Eugene I. Shakhnovich

If enough mutations push an essential protein towards an unstable, non-functional structure, the organism will die. Shakhnovich’s group found that for most organisms, including viruses and bacteria, an organism’s rate of genome mutation must stay below 6 mutations per genome per generation to prevent the accumulation of too many potentially lethal changes in genetic material. (Link, Link-2, Link-3)

For viruses in particular, the limiting mutation rate was found to be just 2.5 mutations per genome per generation (Link). This is the total mutation rate, not just the detrimental mutation rate. Also, the population here is assumed to be infinite in size. For finite populations the maximum tolerable mutation rate would obviously be smaller. The smaller the population, the lower the mutation rate that can be tolerated without an eventual genetic meltdown.

But what about the effect of beneficial mutations?

“Whitlock included beneficial mutations and calculated that N-crit ~(U-deleterious/U-beneficial)^1/3, which depends only on the balance of beneficial to deleterious mutations and not on the mutation rate itself. Both of those examples contradict our results, which show that N-crit and τ depend dramatically on |U|. The dominant reason for the discrepancy is that those authors assumed that deleterious mutations occur “one at a time,” which is not true when the rate that mutations are introduced (U) exceeds the rate at which selection removes them (~1/s). When U/s≫1, the population experiences “Hill-Robertson interference”, which both accelerates extinction and also makes analytic solutions intractable.” (Link)

The nail in the coffin, of course, is the realization that the detrimental mutation rate is significantly higher than Ud = 3 or even Ud = 6 for humans. The original estimate of Ud = 3 was based on the notion that over 95% of the human genome is not functional. Of course, we now know that this notion is mistaken. The majority of the human genome is functional to one degree or another. That means that the detrimental mutation rate is much closer to the overall mutation rate for humans – i.e., at least several dozen detrimental mutations per person per generation (if one limits one’s self to only considering the SNP mutation rate. As we both know, the actual nucleotide mutation rate is much much higher than the SNP mutation rate). Now, we’re talking about trillions of offspring needed per couple in each generation to keep up with even the minimum likely detrimental mutation rate.

The conclusion is quite clear to anyone who considers this problem with a candid mind. All slowly reproducing species are inevitably headed for eventual genetic meltdown and extinction. This is simply no rational naturalistic means to explain this very clear problem away. You simply haven’t done the math for yourself or considered this problem in any real detail.

“That you allow for this toxic accumulation as the basis for speciation and generation of allelic variation to me is a glaring contradiction.” – Pauluc

Where is the contradiction? While beneficial allelic variants can and do evolve all the time (especially in large populations), they are vastly outnumbered by detrimental allelic mutations and other mutations within non-coding DNA. There is no contradiction here. These are well-established facts.

That there is a paucity of research on this suggests that the arguments you advance have no traction in genetics perhaps because as I have said many times before is theoretical not real.

What do you mean by “real”? Do you not realize that all scientific theories are, by definition, theoretical? The conclusion of a devolving gene pool is very “real” as far as a scientific theory is concerned – just as “real” as any other scientific theory is “real”. You do realize that science is based on hypotheses and theories, not direct absolute demonstration? – right? There is always the potential for any scientific theory to be wrong – to end up being falsified. Science isn’t about absolute proof, but about statistical probabilities of a theory being correct based on the less than complete information that is currently in hand.

The research that is in fact in hand regarding the build-up of detrimental mutations is quite clear. It is really beyond any serious debate that the vast majority of mutational changes that have a functional effect on DNA are deleterious to one degree or another. This not only makes intuitive sense, it has been demonstrated over and over again under laboratory conditions. As far as removing these detrimental mutations from the gene pools in a meaningful manner, many suggestions have been forwarded, such as eliminating detrimental mutations in clusters. However, no one has come up with a naturalistic mechanism by which such preferential clustering of detrimental mutations might be achieved.

The fact that you do not recognize any way to falsify your notions on this topic removes your ideas from the realm of science. If you really want to call yourself a scientist, there really is no way around the conclusion that the current evidence we have in hand strongly supports the theory that our gene pool is degenerating over time – as are the gene pools of all other slowly reproducing species on this planet.

Sean Pitman
www.DetectingDesign.com

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