I dont think you are really addressing the problem.

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

I dont think you are really addressing the problem. You hopefully suggest, “Many features, of dogs for example, are polygenetic – such as height or color, etc. For example, the determination of coat color and pattern is a polygenic in that these features are controlled by more than one gene or gene complex.”

Indeed that is true but at each of these polygenic sites there are only at maximum 4 possibilities in a [breeding] pair of 2.

That’s right, but a polygenic trait is not governed by a single site. It might help to get a few concepts straight here. “Quantitative traits refer to phenotypes (characteristics) that vary in degree and can be attributed to polygenic effects, i.e., product of two or more genes… Polygenic inheritance refers to inheritance of a phenotypic characteristic (trait) that is attributable to two or more genes and can be measured Quantitatively… Unlike monogenic traits, polygenic traits do not follow patterns of Mendelian inheritance (separated traits). Instead, their phenotypes typically vary along a continuous gradient depicted by a bell curve… Most phenotypic characteristics are the result of the interaction of multiple genes.” (Link)

Sometimes hundreds of genetic loci are involved in governing the expression of a given trait or feature. For example, height in humans is governed by the interaction of some 200 genetic regions. Genome-wide association studies in humans, laboratory animals, and outcrossed domesticated plants such as maize show that the genetic architecture of most phenotypes tested to date—including body size, body mass index, lipid level, and flowering time—appear to be under the control of hundreds of genes, each contributing a very modest amount to the overall heritability of a given trait. This makes a great deal of variety of expression of a given trait possible – even starting with a very small population (such a just two individuals). This is why my brother and I look so different despite having the very same parents. He has dark skin. I have light skin. He is hairy. I’m not. He has dark green eyes. I have light greenish blue eyes. etc. The is also why two dogs can produce a mix of very different looking puppies within the same litter – to include significant differences in color, hair texture, size, etc…

Of course, it not always the case that a wide variety of a phenotypic trait expressions is the result of a large number of genes. When it comes to modern dog breeds in particular, it seems like relatively few genetic regions of large phenotypic effect underlie most traits.

For example, dog size (the variation of which is greater across dog breeds than in any other terrestrial species) seems to be controlled mainly by six genetic regions (CFA15.44226659, CFAX.106866624, CFA10.11440860, CFAX.86813164, CFA4.42351982, and CFA7.46842856) – with a few dozen other more minor genetic influences. “The signal on CFA15 corresponds to the location of IGF1 which encodes a growth factor previously described to control a significant proportion of size variation across dog breeds. The CFA10 signal corresponds to the location of HMGA2, a gene known to affect body size variation in humans and mice. Both HMGA2 and a locus corresponding to the CFA7 signal, SMAD2, have been previously associated with dog body size. In contrast, the signals on CFA4 and CFAX hits have not previously been associated with body size variation in dogs. Interestingly, the CFA4 signal contains (among other genes) the STC2 locus, a known growth inhibitor in mice. The two signals on the X chromosome lie in separate LD blocks that each contains dozens of genes.”

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000451

So, although such traits in dogs are controlled by fewer genetic regions, it seems quite clear that far more than just “4 possibilities” could be produced by a single breeding pair when it comes to most phenotypic traits – depending upon the combination of these genetic loci and how they control the expression of a given trait.

Of course, “in all six regions, wolves are not highly polymorphic” – as would be expected since wolf morphology is fairly uniform (not having been bred to highlight unique morphologic features that could be isolated in relatively short order). Of course, there are additional allelic options, based on unique mutations, within modern dogs, as compared to the wolf…

For example, the short stubby legs of Dachshunds, Basset Hounds, Corgis, and the like have an extra copy of a gene that codes for Fibroblast Growth Factor 4 (FGF4). This extra gene is a mutated retrogene. Neither the introns nor the upstream promoter sequences of the gene are present in the inserted retrogene. However all exons are present, with no alterations in the coding sequence, as well as the 3’ UTR and poly-A tail – characteristic of retrotransposition of processed mRNA. The lack of introns normally found in FGF4 genes causes the retrogene version to malfunction. In short, this malfunctioning retrogene results in the overproduction of FGF4 transcript. The “atypical expression” of the FGF4 transcript in the chondrocytes apparently causes the inappropriate activation of one or more of the fibroblast growth factor receptors – such as FGFR3. An activating mutation in FGFR3 is responsible for > 95% of achondroplasia cases, the most common form of dwarfism in humans, and 60–65% of hypochondroplasia cases, a human syndrome that is more similar in appearance to breed defining chondrodysplasia (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748762/). In other words, this overproduction of FGF4 is thought to disturb the normal process of limb growth during fetal development, such as turning on key growth receptors at the wrong time, leading to short legs in dogs. What happens is that the development of long bones is curtailed due to calcification of growth plates, resulting in short legs with a curved appearance.

This example illustrates the fact that dramatic phenotypic differences can be produced by gene dosage alterations – i.e., an increase or decrease in gene products. Mutations that cause an over or under production of gene products are not uncommon and can be realized in relatively short order – especially in larger populations.

Remember, it is far far easier for mutations to cause a loss or disruption or even a gain of the same basic type of pre-established functionality vs. the evolution of entirely novel, qualitatively novel, functionality – which does not happen at all beyond very low levels of functional complexity.

This is why such novel features in various breeds, such a dog breeds, or even “species” that were derived from the same ancestral gene pool, can be realized in such short order. They really have nothing truly new, qualitatively new, beyond very low levels of functional complexity – compared to what their original parents had. Almost all examples of the evolution of “new” functional traits or alleles are based on the disruption or loss of a pre-existing trait or functional system. And, those occasional examples of evolution where qualitatively novel functional systems are produced in observable time are all at very very low levels of functional complexity (requiring a minimum of no more than a few hundred specifically arranged amino acid residues).

That is why I argue that the current phenotypic variety of breeds, such as dogs, is based on front-loaded genetic information with very little if any qualitatively novel traits evolving which were not based on the quantitative increase or decrease of expression of pre-existing genetic elements – something that can be achieved in very short order.

I am again confused. Are you arguing for dogs derived from 2 wolves or not? If you take the genesis account literally which I understand you do, dogs are unclean and you must consider that they are therefore derived from the most severe genetic bottleneck possible.

What I’m saying here is that it would be possible to produce all or nearly all the phenotypic diversity of modern dog breeds within a very short time starting with only two individuals. I’m not quite sure why you think longer periods of time would be required for selective breeding to produce essentially the same degree of phenotypic variety that we see today? Where is the limiting factor here?

It would help your argument if you could point to an example of a reintroduction program where there was success with 2 genetically isolated animals. I certainly cannot find any.

If you care to read the paper on reintroduction of wolfs into yellowstone

http://www.ncbi.nlm.nih.gov/pubmed/17877715

You will see they followed the standard practice built up based on long experience and reintroducing around 40 animals. [It is argued whether sustainable populations are around 30 or if 50 are needed)

Which brings us back to our previous discussion about declining genomic quality over time. As already explained in some detail, this decline is due to the continual build-up of detrimental mutations in the gene pools of all slowly reproducing creatures far far faster than natural selection can get rid of them. The death rate required for natural selection to deal with this problem is simply far too high. That is why inbreeding within small groups of animals or people is such a big problem today. It enhances odds of the fixation of detrimental mutations within a population – resulting in a greater chance of genetic meltdown and extinction within a shorter time span. This is also why many modern dog pure-breeds suffer from far more genetic diseases than do hybrid dogs.

There is also, of course, the problem of the dangers of living in the wild – of dealing with random accidents, injuries, sickness, disease, infertility, ext. Increasing the population size helps to alleviate these problems when trying to start a new colony.

The experience with 4 avian species again shows that populations with low genome equivalents are subject to significant and life threatening inbreeding and loss of genetic diversity

http://www.ncbi.nlm.nih.gov/pubmed/20825445

2 genome equivalents is clearly in the unsustainable range according to all the current practical and theoretical models of population genetics.

In modern times, yes. Thank you for highlighting my point. This was not the situation, however, when gene pools were much closer to their original creation and had not yet built up so many detrimental mutations…

I really don’t know why you seem to be continually arguing for naturalistic mechanisms for scenarios around the miraculous global flood account. Can’t you accept that derivation of all populations from the ark is genetically untenable and accept it as miraculous. Creation science is intrinsically miraculous; turtles all the way down. Just accept it and don’t pretend it is some scientific hypothesis that can be tested by experiment. As prof Kent argues it is even worse because you not only try to argue a particular interpretation is scientifically valid but then pin your faith on your ability to argue the scientific validity. It’s a miracle. Move on to the consequences and you might not find it is so foundational.

There is no need to invoke God to explain the phenotypic diversity of living things beyond His original programming of the parental population – His “front-loading” of the gene pools if you will. God did not need to step in and create novel alleles within wolves or dogs in order for the diversity of dog breeds to be realized in very short order via natural processes that have been in place since the beginning of life on this planet. It is simply your lack of understanding that makes you think that a subsequent Divine miracle, or an ongoing series of miracles of deliberate design, would have to have been required. What? would you really have me believe that God was the one who stepped in and deliberately created the retrovirus FGF4 gene for the “inappropriate activation” of FGFR3? so that modern dogs could have stumpy legs? I suppose God also causes achondroplasia in humans? Come on now…

The same is true for the nature of the geologic / fossil records. No Divine miracle is required to explain most of their features from a Biblical perspective. Sure, there are still unanswered questions. However, the weight of evidence, science itself (true science that is), strongly supports the claims of the Bible. Faith in the reliability of the Bible as the true Word of God need not be blind or indistinguishable from wishful thinking…

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