I have given you references to real studies with data

Comment on Southern Adventist University opens Origins Exhibit by Sean Pitman.

I have given you references to real studies with data that indicate that 2 animals is unquestionably a non-viable populations in any conservation breeding program which is the best we have in terms of replicating the ark scenario.

Not only have modern breeds of dog been based on very limited numbers of breeding pairs, this experiment has been repeated with foxes (see nova video linked above).

Beyond this, as already explained, your arguments are entirely based on gene pools that have built up large numbers of detrimental mutations. Mammalian gene pools, as with all other slowing producing creatures, are heading downhill. That is why the ancestral parental gene pool was much better off than it is today. You really have no rational basis to argue otherwise beyond your dedication to neo-Darwinism. The evidence of genetic deterioration far faster than natural selection can keep up with it is quite clear for all slowly reproducing creatures.

Further I have suggested that doing the math does not allow one to even conceive of vast phenotypic potential on the basis of allelic variation in a population of 2.

Oh really? I’ve yet to see you do much of any math. What math are you talking about that significantly limits the phenotypic trait potential of a breeding pair of wolves? – to a point where similar phenotypic diversity, on a practical level, could not be achieved without a basis in novel mutations?

You continue digging the hole by deprecating the role of new mutations and insisting that there is front loaded potential by a mechanism you cannot define in accepted genetic terms.

The role of new mutations is largely detrimental/degenerative – as you should know. I’ve listed examples of such in this same thread. Occasionally, of course, certain benefits do arise by novel mutations, but not beyond very very low levels of functional complexity – as I’ve also explained.

Having raised the issue of polygenic nature of phenotypic traits as an explanation of the vast potential I thought you would be familiar with some of the more foundational concepts in genetics. From your responses I once again seem to be in error. What is the conventional view.

The current concept of a gene is of a sequence of DNA in the genome that codes for a protein and has associated regulatory elements and non-coding RNA.

Pretty good, except for the fact that the modern concept of a “gene” or functional genetic element has been expanded by the discovery that protein-coding genes do not contain the majority of functional information within the genome. “Non-coding genes” occupy the majority of the genome and control the “coding” genes as a blueprint dictates how the bricks and mortar are to be applied in the construction of a building.

But anyway, I digress…

The organism at the level of the organelle cellular, organ, or organism is sustained by biochemical pathways and structures that rely on these genes.

Depending on levels of redundancy loss of a gene may affect the function and result in a particular change in the organism which is recognized by observation grossly biochemically or microscopically. This is often called a trait as in sickle cell trait or phenotype where there is a particular shape of the red cells. Usually this there are multiple characteristics associated with this trait. For Sickle cell disease this is rapid clearance of the red cells from the blood and anaemia. Trouble with red cells in the circulation leading to blocked blood vessels and resistance to malaria infection of the red cells.

So far so good . . .

Mendelian traits are those that map to a single gene locus and result in a phenotypic change. Sickle cell is one that maps to a gene coding for part of the haemoglobin molecule.

Right . . .

Now production of red cells containing haemoglobin red cells is dependent on very many genes. From the genes such as eythropoietin that regulate amount of haemoglobin and red cells that are produced in erythroblasts and progeny cells in the bone marrow to the genes controlling the proteins and carbohydated structure of the red cell membrane all are related to the red cell physiology and physical characteristics or phenotype.

That’s right . . .

Now say a population of people move to the Himalayas or the Andes. They need more red cells. The response will be that those in the population that have the best ability to produce red cells will have better ability to carry oxygen in the presence of low oxygen tension and will have better fitness. This trait of high altitude fitness is unlikely to be a mendelian train but will be a polygenic trait. The initial measure of ability to carry oxygen will have something like a Gaussian distribution. If there is within the population multiple genes with some polymorphism or variability in function even through within that one gene it has minimal overall effect the selection will be on multiple such genes so that the fittest population with the high oxygen carrying phenotype will have a genotype that is has been selected for the phenotype. It is a not a selection of genes one at a time but a simultaneous selection. Allele frequency at multiple loci will be changes within a very short time. Now if one of the people in the population has a new mutation that has better function it will be quickly fixed in the population and carried along with a cluster of more or less useful genes. In other words selection integrated across a large number of genes.

Also true . . .

To argue about potential sequence space and absolute probabilities is nonsense.

How so? How do you determine the odds that any novel system of function, where all of the amino acid residues must work in a specific arrangement with each other, will be realized in a given span of time by random mutations? The fact is that you don’t make this determination at all. You don’t consider the math or the odds at all. You just assume that it happens without considering the level of functional complexity involved with finding novel beneficial sequences in sequence space.

This concept I would have thought was familiar to you as even Sanford in his book “Genetic entropy” does accept there is phenotypic rather than genotypic selection (see chapter 4 and his cute Princess and the nucleotide paradox).

Of course this concept is familiar to me. It is a correct concept. There is phenotypic selection that affects the underlying genotype. I’ve already gone into this before with you, if you will recall. Your problem is that you do not consider the level of functional complexity involved. Low-level systems can and do evolve all the time. However, as you consider higher and higher levels of qualitatively novel functional complexity, the evolvability of these higher level systems drops off – exponentially.

What Sean is arguing is that things like size and coat colour in Dogs that are clearly polygenic the cis interactions between mjultiple variable genes can compensate for a lack of polymorphism at any genetic locus imposed by a population size of 2.

That’s right.

If we assume that dog size depends on products of pathways involving 5 genes [in fact this is vastly overestimating it as IGF-1 seems to be the predominant determinant], then in a population of 2 there are maximum of 4 alleles at 5 loci. The possible genotypes assuming absolutely no genetic linkage are then 4^5 = 1024 compared to 20^5 = 3.2 million for a population of 20 with the same level of genetic heterogeneity and allelic variation.

A population of 2 with complete heterogeneity over 5 loci is not what is seen in extant populations; but allowing Sean’s assumption in any lottery I would take my chance with 3 millions rather than 1000 tickets.

As already noted, size in dogs is primarily controlled by six genetic regions and dozens of genes with lesser influence (compared to humans were height is governed by >200 genes). The sequence space is 4^6 = 4096 based on just these six primary controls for size alone (not counting the dozens of other genes that are involved in more minor ways here). This seems like adequate control for this particular trait. How much more control over size one would want I don’t know?

You seem to be totally confusing a polygenic family and a polygenic trait.

How is that?

The MHC is not a phenotype or a function. It is a region of 2 megabase or more contains a family of genes, likely of common origin, in tight linkage dysequilibrium and in which the different loci can be ascribed particular functions.

The Major Histocompatibility Complex (MHC) is indeed a collection of different types of proteins that are collectively involved with appropriate immune system function – a polygenic trait. Are the different elements of the MHC complex individually selectable? Certainly . . .

HLA-B codes for the alpha chain of class I molecules. This encodes the CDR region of the molecule that is the site that can bind to specific 9-11 amino acid peptides that have a structurally complementary sequence to the class I alpha chain. The high levels of polymorphism at this locus determined the phenotype or what will bind to that molecule and be recognized by a CD8 or cytotoxic T cells. This is the phenotype that is subject to selection; the allele that can recognize a particular pathogen structure.

Yes . . .

Presence of the allele HLA*B57 has a clear survival advantage in HIV infection by recruiting particularly effective CD8 T cells that recognize that class I molecule. The HLA*B5701 haplotype as well as 5702 and 5703 and the related 5801 all have ability to create effective HIV specific CTL that determines the good responder phenotype not because of the associated changes outside the peptide binding groove or nucleotide variation elsewhere in the gene that defines the 4 digit specificity.

Right . . .

Geneticist do not see any qualitative difference between allelic variation and mutation except in frequency within a population. There is absolutely no reason to conceptualize some distinction between changes in nucleotide sequence because of some imagined ancestory. It is up to you to provide a model and evidence if you wish to do so.

Again, I’m not sure what you’re your main point is here? Of course mutations produce allelic variations! Where have I even suggested otherwise? In fact, some systems, especially immune systems, are based on the programmed production of genetic variations to produce a huge variety of antibodies (before non-self antigens are even encountered).

It is just that random mutations do not produce qualitatively novel systems of function beyond very low levels of functional complexity is all. That’s the main point here. This is the point that you’re simply not addressing in any of your responses thus far.

Also, what do any of your arguments have to do with my statement that the current phenotypic variety of animals is largely based on pre-programmed or “front-loaded” information? – that many current allelic options are detrimental or degenerative in nature? – or that there are no examples of qualitatively novel functionality beyond very low levels of functional complexity arising by RM/NS?

I look forward to reading you PLOS one or PLOS genetics paper on the recognition and importance of mutations with “very very low levels of functional complexity”.

I do not dispute the impact or even the importance of mutations with low-level functional effects. That’s not even in question here. Such mutational effects can and do happen – very commonly in fact in larger populations. That is why it doesn’t require long periods of time for such mutations to be realized. What cannot be explained by you or anyone else coming from a Neo-Darwinian perspective is the origin of qualitatively novel systems of function that require a minimum of more than 1000 specifically arranged amino acid residues.

Sean Pitman
www.DetectingDesign.com

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Sean Pitman Also Commented

Southern Adventist University opens Origins Exhibit
@pauluc:

If I may summarize our previous posts on allelic variation, SNPs and speciation
You suggest

1] There was frontloading of genetic information in a breeding pair for most species 2349-2348 BC.

The frontloading was at the time of creation by the Creator (less than 10,000 years ago), with a genetic bottleneck at the time of the Noachian Flood some 4,000 or so years ago . . .

2] Variation leading to speciation within kinds was by genetic mechanisms of allelic variation from the original gene pool. Maybe 10-20% of the variation can be attributed to this front loading.

It depends what type of variation you’re talking about. All of the variation beyond very low levels of functional complexity is the result of frontloading . . .

3] Most of the allelic variation and SNPs seen in species today has arisen by random mutation within the populations derived from this starting population of 4 haplotypes. ie 80-90% of the variation within species derived from “kind” ancestor.

At low levels of functional complexity, yes, the vast majority of allelic variations are the result of random mutations.

4] Most (80-90%) of the phenotypic differences seen between species has occurred by natural selection and genetic drift.

Within the same basic “kind” of gene pool – yes.

5] Any differences due to RM/NS after selecting the front-loaded pair can only confer very very low level complexity.

That’s right.

6] There is a barrier of 1000fsaar that limits any ability to generate anything novel and complex within this 80-90% of new mutations.

Yes.

Apropos of the recent paper:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310774/?tool=pubmed

How do you modify your model of constraint by 1000fsaar to account for the role of SNPs in determining the effects of non-coding regulatory elements? In this context any discussion of hamming distance is really examining the edge effect of minimal relevance. I should not have to explain how this is particularly germane and impacts your discussion about genetics of feathers and the regulation of genes controlling feathered phenotype.

Non-coding regulatory elements are key to the building of complex systems within living things – far more important than are the protein-coding genes themselves (which function more like bricks and mortar that can be used to create many different types of buildings). SNPs can affect these regulatory elements, obviously. However, SNPs cannot affect these regulatory elements in a way that causes them to produce a qualitatively novel type of “building” with the “bricks and mortar” – beyond very low levels of functional complexity of course. In other words, you have to ask yourself the odds that a single point mutation to a regulatory non-coding sequence, or any other type of mutation, will result in a change in the location of the final product to an entirely novel island in sequence space that has a qualitatively unique function that requires a minimum of more than 1000 specifically arranged amino acid parts? That just doesn’t happen. There are no examples of this anywhere in literature – period.

If you would actually sit down and do the math, you’d see why. Sequence space has a fairly uniform distribution of potentially viable sequences/structures. As the minimum size and or specificity of the system under consideration increases in a linear manner, what do you think happens to the ratio of potentially viable/beneficial vs. non-viable/non-beneficial sequences in sequence space? The number of non-viable sequences increases in an exponential manner compared to the potentially viable sequences. The means that the viable sequences become more and more isolated in sequences space, dramatically so, with each step up the ladder of minimum size and/or specificity requirements. This means, of course that the minimum likely gap distance between viable sequences in different island clusters increases in a linear manner with each increase in the minimum size and/or specificity requirements. And, this means, of course, that the average time needed for any kind of random mutations needed to traverse the linearly increasing gap distances increases exponentially.

Now, tell me, how do you solve this sequences/structure space problem at increasing levels of functional complexity? Do you really not see the exponential nature of the problem? There is really no point in further discussion if you will not discuss this particular question. I really don’t understand your continued reluctance to substantive address such problems or consider the statistical basis for your own evolutionary assumptions. Why don’t you sit down and actually do a few calculations? Why not calculate the odds, for yourself, of any kind of mutation or series of mutations in any kind of coding or non-coding region evolving any kind of qualitatively novel system at various levels of functional complexity?

Give it a shot already. What could it hurt?

Sean Pitman
www.DetectingDesign.com

Southern Adventist University opens Origins Exhibit
@pauluc:

Since you havent responded to my request to identify in the genomic comparison of mammalian species or primates with the instances of where the 1000fsaar criteria limiting the sequence differences, I suggest an alternative.

But I have responded to this question at least a couple times in this thread. Please go back and review these responses to you and Jeff Kent.

Please provide insights on this recent paper from Kate Sullivans group on Human Accelerated Regions that are proposed to be contributors to the differences between humans and Chimps particularly in limb and brain development. Im interested in the comparison between human SNPs and the varying presence of these SNPs in chimp, Neandertal and Denisova genomic sequences.

Differences between human and ape brain development are based on more than SNPs (which would produce quantitative differences in form and function, but not produce qualitative changes beyond very low levels of functional complexity).

As already noted a few posts above in this thread, humans and apes are quite different in various respects, to include brain structure and function – which is thought to be based on numerous differences in genetic regions that code for miRNAs (around 8% of which are human specific).

“miRNAs recently have been implicated in synaptic development and in memory formation. As the species specific miRNAs described here are expressed in the brain, which is the most complex tissue in the human body, with an estimated 10,000 different cell types, these miRNAs could have a role in establishing or maintaining cellular diversity and could thereby contribute to the differences in human and chimpanzee brain … function.”

Eugene Berezikov, Fritz Thuemmler, Linda W van Laake, Ivanela Kondova, Ronald Bontrop4, Edwin Cuppen & Ronald H A Plasterk, “Diversity of microRNAs in human and chimpanzee brain”, Nature Genetics, Vol 38 | Number 12 | December 2006 pp. 1375-1377.

The Y-chromosome is even more unique. A study published by Nature in early 2010 showed many striking differences between human and chimp chromosome structure, gene content, and even qualitatively unique genes between the two species.

As far as looking at specific genes, the chimp and human Y-chromosomes seem to have a dramatic difference in gene content of up to 53 percent. In other words, the chimp is lacking approximately half of the genes found on a human Y-chromosome. Because genes occur in families or similarity categories, the researchers also sought to determine if there was any difference in actual gene categories. They found a shocking 33 percent difference. The human Y-chromosome contains a third more gene categories, entirely different classes of genes, compared to chimps.

Hughes, J.F. et al. 2010. Chimpanzee and human Y chromosomes are remarkably divergent in structure gene content. Nature. 463 (7280): 536-539.

For further discussion see:

http://www.detectingdesign.com/pseudogenes.html#Key

I am sure you see P Troglodyes as entirely unrelated to man but I am a little unclear on your model of origins in terms of relatedness of Neandertal and Denisova hominids to man. Are they the children of Adam, Noah or neither? How do you account for any sharing of SNPs, the HAR and the development of pehnotypic differences by SNPs?

Neandertals and Denisova are human, descendants of Noah. They are simply ethnic variations of humans. Even mainstream scientists think that they could interbreed with each other to produce viable and virile offspring.

Of course there will be SNP differences between modern humans and Neandertals and other ancient ethnic groups – as there are between modern ethnic groups. And, these SNPs may be associated with functional differences – but not beyond low levels of functional complexity (usually only quantitative differences of the same basic type of gene function).

As far as the HAR-1 RNA, there are 18 character differences between humans and chimps (out of 118 characters/nucleotides). These differences are thought to play some role in the development of our brain differences, but no one knows exactly what role. Obviously, there are many structural and functional brain differences at high levels of functional complexity. However, there are also many unique non-coding genetic elements that seem to be involved with these differences (as already explained). No single point mutation or small cluster of mutations is going to be able to cross the gap between any qualitatively novel higher level system of function. Again, there are no examples of this in literature – for very good statistical reasons.

Another paper that cries out for your interpretation including the point at which ignorance about the 1000fsaar limit has blinded this group of scientist.

http://www.ncbi.nlm.nih.gov/pubmed/22398555

Critique below the abstract would be most helpful in seeing the errors.

Where in this paper is there any discussion of levels of functional complexity and how mutations can generate qualitatively novel systems at high levels of functional complexity? Remember, we aren’t just talking about quantitative differences in functionality here. We are talking about qualitatively novel differences beyond low levels of functional complexity. We need some actual math here – a few statistical calculations as to the odds that the just-so stories in papers like this might or might not actually be likely to be realized in a given span of time. Please do quote for me the relevant portion of this or any other paper along these lines.

Don’t just give me a bunch of references without any quotes or commentary (aka: reference mining). Show me that you actually understand the problem under discussion by, well, discussing it for a change with the use of quotes that you think are relevant. That would be most helpful…

Sean Pitman
www.DetectingDesign.com

Southern Adventist University opens Origins Exhibit
@Professor Kent:

Again, the question is why does one accept the Bible among so many compete options as the real Word of God? If this choice is based on blind faith without any rational basis or appeal to the weight of empirical evidence, what you have is nothing much more useful than wishful thinking… not the kind of faith that has the power to provide a solid hope in the future for most rational people – especially in the face of very difficult trials or even the threat of torture and death.

What you’re asking people to do is to accept the Bible without really considering the weight of empirical evidence or any additional evidence that may contribute to the current weight of evidence for or against the Bible’s credibility. That’s simply not a rational expectation. Certain God does not expect anyone to believe without a rational basis for belief or faith set upon the weight of evidence that would appeal to the candid mind.

In this line, we are talking about what paid representatives of the SDA Church are teaching and/or preaching in the name of the Church. The Adventist Church, as an organization, simply cannot afford to pay people to go around teaching our young people that the best we have to support the Adventist position on origins is faith that is effectively blind to the otherwise overwhelming scientific basis for neo-Darwinism. That simply isn’t helpful to Adventism. Those who believe in neo-Darwinism, however honest and sincere they may be (and there are many in this category) cannot effectively represent the Adventist perspective on several fundamental doctrinal positions within our schools…

Sean Pitman
www.DetectingDesign.com