Humans DNA is 99% similar to that of chimps?

[mark kennedy]

I'm stuggling with this right now. I've read that human dna is 99% similar to the dna of chimps. How do we as creationists reconcile that to our belief that we are not related to apes?

First of all we are not 99% simular to chimpanzees, it is more like 96% simular and about 29% identical in the protein coding genes. Secondly, the differences are enormous given a time frame of 5-7 million years. There are five million indels (insertions/deletions) in the nucleotide sequence that total about 90 million nucleotides. In order for this to happen in the estimated timeframe it would require something like 1 indel, 1-59,000 nucleotides being altered in the respective genomes every year for five million years. That is in addition to 35 million single nucleotide polymorphisms and about 20 million nucleotides worth of chromosomal rearrangements as long as 20 million nucleotides.

This is from the latest scientific research on the subject.

"Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements."​

http://www.nature.com/nature/journal/v437/n7055/full/nature04072.html

The mutation rate for human beings is about 10^-8 which is basically a decimal point followed by 8 zeros. Humans diverge from one another by one tenth of 1%. Whoever told you we are 99% simular to chimpanzees is either misinformed, willfully dishonest are something worse.

The problem is changing indels totaling 90 million nucleotides in 5 million years. You do the math and compare it to the substitution rate in living systems as directly observed and demonstrated in modern genetics. You are not going to find an answer to this problem for evolution but they would like you to believe they allready have.

 

[Gukkor]

Have you ever seen any atheists argue that the Bible is true, but in a non-scientific way? Isn't that something only TEs argue? That is where the main difference is.

As rmswilliams and Assyrian have excellently exposited, it really isn't surprising that TEs and atheists agree in terms of science. What is surprising, then, is that YECs and atheists agree in terms of the Bible. Why do I say that? Because atheists and YECs agree that "if creationism is false, the Bible is false".



What program? It has been pointed out that the percentage depends on how the difference is measured. For example, I may have gotten only 70% on a test, but if almost nobody else got above 70%, then I would end up in the 99% percentile, so you could either say that my results are "70%" or "99%", depending on which score you take.



And the YEC position is like a detective who, before seeing the body, decides that Merlin the magician killed the victim.

If I show him a garroted body, a garrot with Suspect A's fingerprints, and Suspect A with no alibi, the detective says "Merlin zapped him, made the garrot marks, put Suspect A's fingerprints on the garrot, and gave Suspect A amnesia so that he couldn't remember where he was during the crime."
If I show him a body with waterlogged lungs, clippings from under the victim's fingernails which match Suspect B's DNA, and Suspect B who was seen within 50m of the swimming pool during the time of murder, the detective says "Merlin zapped him, filled his lungs with water, put Suspect B's tissue under the victim's fingernails, and hypnotized the passerbys to imagine that they saw Suspect B at the pool."

Is there actually any evidence that Merlin killed the man? No, because there is no way to convince the detective that it wasn't Merlin who killed the man.

YECism is ultimately unfalsifiable and therefore isn't science.

Sadly, I'm afraid I must agree. I don't hold any enmity toward YECs, but I'm rather stunned by the degree to which many of them are willing to deny science, which should in fact be seen as one of the greatest testaments to God's power and glory.

 

[rmwilliamsll]

First of all we are not 99% simular to chimpanzees, it is more like 96% simular and about 29% identical in the protein coding genes.

WASHINGTON, Wed., Aug. 31, 2005 - The first comprehensive comparison of the genetic blueprints of humans and chimpanzees shows our closest living relatives share perfect identity with 96 percent of our DNA sequence, an international research consortium reported today.
...
The consortium found that the chimp and human genomes are very similar and encode very similar proteins. The DNA sequence that can be directly compared between the two genomes is almost 99 percent identical. When DNA insertions and deletions are taken into account, humans and chimps still share 96 percent of their sequence. At the protein level, 29 percent of genes code for the same amino sequences in chimps and humans. In fact, the typical human protein has accumulated just one unique change since protein and humans diverged from a common ancestor about 6 million years ago.

from: http://www.genome.gov/15515096

so far, confirmed with several articles.

Secondly, the differences are enormous given a time frame of 5-7 million years. There are five million indels (insertions/deletions) in the nucleotide sequence that total about 90 million nucleotides.

Two different things. one is number of potential mutation events, indels. The other is the number of effected DNA bp's.
5M events is .5 per year fixed in the chimp and human diverging populations since the last common ancestor. (think of it as mutation from human upto LCA then down to modern chimp, both of us: chimp and human are roughly the same genetic distance from the LCA)

What is 1/2 mutation per year? fast, slow, just what?

so how do evolutionary geneticists measure this rate?

Rate of Evolution

To assess the rate of evolution for each gene, estimated KA, is the number of coding base substitutions that result in amino acid change as a fraction of all such possible sites. Because the background mutation rate varies across the genome, it is crucial to normalize KA for comparisons between genes. A striking illustration of this variation is the fact that the mean KA is 37% higher in the rapidly diverging distal 10Mb of chromosomes than in the more proximal regions. Classically, the background rate is estimated by KS, the synonymous substitution rate (coding base substitutions that, because of codon redundancy, do not result in amino acid change).

from: http://72.14.209.104/search?q=cache...ities+mutation+rates&hl=en&gl=us&ct=clnk&cd=3
google rendered power point slides.
nice easy introduction.

there is another more complete introduction to the ideas at:
http://www.genome.org/cgi/content/full/12/9/1350

there is an ICR article that makes the same mistake, confusing mutation events with nucleotides at:
http://72.14.209.104/search?q=cache...ties+mutation+rates&hl=en&gl=us&ct=clnk&cd=32

http://www.nature.com/nature/journal/v437/n7055/full/nature04072.html

The mutation rate for human beings is about 10^-8 which is basically a decimal point followed by 8 zeros. Humans diverge from one another by one tenth of 1%. Whoever told you we are 99% simular to chimpanzees is either misinformed, willfully dishonest are something worse.

The problem is changing indels totaling 90 million nucleotides in 5 million years. You do the math and compare it to the substitution rate in living systems as directly observed and demonstrated in modern genetics. You are not going to find an answer to this problem for evolution but they would like you to believe they allready have.

the problem with your argument is that it assumes 1 mutation fixed in the population means 1 nucleotide changed. That is not what happens, although i have been unsuccessful at finding the average number of nucleotides involved in a indel event. Although all the quoted articles make it clear that large pieces of DNA have been modified by single mutation events.

The analysis of modest-sized insertions reveals approx32 Mb of human-specific sequence and approx35 Mb of chimpanzee-specific sequence, contained in approx5 million events in each species

although this implies that (32+35)/5=13bp/event, i think.
quote from the nature article referred to several times.

one of the best and readable articles i came across is at:
http://home.att.net/~DNAPaleoAnth/MoleCalib.html
an individual, not a scientific paper. better as an introduction to the relevant issue.


.

 

[mark kennedy]

from: http://www.genome.gov/15515096

so far, confirmed with several articles.

That's right, the scientific research is the basis for my original statement. The mutation rate necessary is astronomically high when compared to the mutation rate in any living system known to man.

Two different things. one is number of potential mutation events, indels. The other is the number of effected DNA bp's.

The indels are simply differences in the respective genomes. When there is one sequence not present in the other it is an insertion, when it is absent it is refered to as a deletion. They know full well what the potential is for an indel, they are 98% neutral with the vast majority of the balance being deleterious.

5M events is .5 per year fixed in the chimp and human diverging populations since the last common ancestor. (think of it as mutation from human upto LCA then down to modern chimp, both of us: chimp and human are roughly the same genetic distance from the LCA)

Nonsense, the 5 million indels are 2-56,000 nucleotides a that add up to over 90 million nucleotides in 5-7 million years. Let's say this is a gross underestimation of the time frame and it actually 10 million years since the most recent common ancestor (MRCA). 10/90=9 per year for ten million years. This does not include the 35 million SNPs or the chromosomal rearrangements. The indels represent 5 million indel events, not nucleotides. The nucleotides are 1-56 thousand nucleotides in length.

"The analysis of modest-sized insertions reveals 32 Mb of human-specific sequence and 35 Mb of chimpanzee-specific sequence, contained in 5 million events in each species (Supplementary Information 'Genome evolution' and Supplementary Fig. S5). Nearly all of the human insertions are completely covered, whereas only half of the chimpanzee insertions are completely covered. Analysis of the completely covered insertions shows that the vast majority are small (45% of events cover only 1 base pair (bp), 96% are <20 bp and 98.6% are <80 bp), but that the largest few contain most of the sequence (with the 70,000 indels larger than 80 bp comprising 73% of the affected base pairs) (Fig. 5). The latter indels >80 bp fall into three categories: (1) about one-quarter are newly inserted transposable elements; (2) more than one-third are due to microsatellite and satellite sequences; (3) and the remainder are assumed to be mostly deletions in the other genome."

[note the bolded portion]

What is 1/2 mutation per year? fast, slow, just what?

That is absurd, pure and simple. I don't know where you are getting this 1/2 per year but even at that it is ridiculasly high. That adds up to ten per reproductive generation (20 years), fixed genome wide for millions of years. This simply does not happen in any living system known to man.

so how do evolutionary geneticists measure this rate?

By comparing nucleotide sequences over a specified number of generations of course.

This statement...

"The DNA sequence that can be directly compared between the two genomes is almost 99 percent identical."

has been conclusively proven to be absolutly false. Your source material is giving you outdated and bogus statistical information.

there is another more complete introduction to the ideas at:
http://www.genome.org/cgi/content/full/12/9/1350

The article simple speculates on the causes of selection, there is nothing concrete in any of it.

there is an ICR article that makes the same mistake, confusing mutation events with nucleotides at:
http://72.14.209.104/search?q=cache...ties+mutation+rates&hl=en&gl=us&ct=clnk&cd=32

ICR does not make a mistake here, they simply have not realized how great the differences are yet.

the problem with your argument is that it assumes 1 mutation fixed in the population means 1 nucleotide changed. That is not what happens, although i have been unsuccessful at finding the average number of nucleotides involved in a indel event. Although all the quoted articles make it clear that large pieces of DNA have been modified by single mutation events.

For an insertion nucleotides are inserted, for deletions nucleotides are deleted...thus changed. That is what an indel event is and the one that would be required would have had to be:

"70,000 indels larger than 80 bp comprising 73% of the affected base pairs"

I suggest you read the article and not rely so much on google searches to produce links and pedantic one liners as commentary. The Nature article represent 3 years of research by dozens of world class researchers producing an entire genome sequence comparison.

although this implies that (32+35)/5=13bp/event, i think.
quote from the nature article referred to several times.

I think you must be refering to this:

"The analysis of modest-sized insertions reveals 32 Mb of human-specific sequence and 35 Mb of chimpanzee-specific sequence, contained in 5 million events in each species "

Mind you, these are the modest size insertions in the respective genomes and there are also 35 million SNPs and 8 major chromosomal rearrangements up to 4 million nucleotides long.

one of the best and readable articles i came across is at:
http://home.att.net/~DNAPaleoAnth/MoleCalib.html
an individual, not a scientific paper. better as an introduction to the relevant issue.


.

Ok, I don't know what the relevance of the last link is but if it does something for you, great. Maybe you would like to know how many gross structural changes are involved in the protein coding genes at an amino acid sequence level.

"Human&#8722;chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized."

http://www.nature.com/nature/journal/v429/n6990/full/nature02564.html

That is 68,000 indels with 83% of the 231 coding sequences showing differences at an amino acid sequence level. Want to know how this would have had to happen in the protein coding genes? This is the basic data they are working from:

"We compared the size of the successfully amplified DNA fragments from 219 indels, of which 193 showed lineage-specific changes in size. Thus, we were able to distinguish insertion from deletion events independently in human and chimpanzee lineages, and to estimate the original state of these regions in the genome of the last common ancestor."

Ok, differences identified right? Now the differences in the protein coding genes:

"Taken together, gross structural changes affecting gene products are far more common than previously estimated (20.3% of the PTR22 proteins, as listed in Supplementary Tables 4 and 5)."

That is just over 20% of the gene products showing gross structural changes. It is vastly more then 99% simular and this last little tidbit might interest you. The chimpanzee genome is 10% longer then the human genome. That means that the nucleotide sequences are only 90% simular when counting the number of nucleotides in the genomes alone. This is an example of the classic measure of divergance applied to comparitive nucleotide sequences in the protein coding regions.

"The neutrality of sequence differences found between orthologous pairs of human and chimpanzee genes can be assessed using KA and KS values (KA/KS1 indicates neutral evolution; KA/KS > 1 indicates positive selection, and KA/KS < 1 indicates negative selection; that is, purifying selection). KA, KS and other related values were calculated for 231 genes on PTR22q, with 10% of the genes having a KA/KS ratio >1"
(DNA sequence and comparative analysis of chimpanzee chromosome 22, linked above)


If you have a pencil handy and a little time you might try to calculate the mutation rate that would be necessary for this to happen. You also have to take into consideration that the brain nearly triples in size in about 2 1/2 million years so natural selection has to be working extra hard on this.

I have talked to TEs about this, science students, a geneticist and one of the authors of the Initial Sequence of the Chimpanzee Genome paper. None of them had an answer for this but it is the YEC who is wrong and the Darwinians who are right. Nevermind that the evidence is pointing to independant linage of humans and apes. The presumption of a LCA for chimpanzees and humans is bullet proof, no matter what the evidence tells us what would have had to happen.

 

[shernren]

If you have a pencil handy and a little time you might try to calculate the mutation rate that would be necessary for this to happen. You also have to take into consideration that the brain nearly triples in size in about 2 1/2 million years so natural selection has to be working extra hard on this.

In terms of phenotypic rates of divergence, a tripling of the brain size in 2.5 million years amounts to less than one darwin of change. Experimental studies reveal evolutionary rates up to thousands of darwins (Finding Darwin's God, quoting OTOH). One darwin compared to that is an astronomically slow rate of divergence, not fast, don't you think?

That is absurd, pure and simple. I don't know where you are getting this 1/2 per year but even at that it is ridiculasly high. That adds up to ten per reproductive generation (20 years), fixed genome wide for millions of years. This simply does not happen in any living system known to man.

I have seen this argument from incredulity for months already without a single resource to show what actual mutation rates are. How do you know that many mutations cannot happen and be fixed simultaneously?

 

[mark kennedy]

In terms of phenotypic rates of divergence, a tripling of the brain size in 2.5 million years amounts to less than one darwin of change. Experimental studies reveal evolutionary rates up to thousands of darwins (Finding Darwin's God, quoting OTOH). One darwin compared to that is an astronomically slow rate of divergence, not fast, don't you think?

9 nucleotides fixed genome wide, per year, for 10 million years is not gradual, it's impossible.

I have seen this argument from incredulity for months already without a single resource to show what actual mutation rates are. How do you know that many mutations cannot happen and be fixed simultaneously?

The mutation rate is 10^-8, it is not a difficult statistic to find if you make any kind of an effort at all. What is more, well over 98% will be neutral which is to say they do nothing at all with the vast majority of the balance being deleterious which means they are harmfull. We have a great disparity between the known divergance rate which is a decimal point followed by 8 zeros. Then there is the rate of fixed nucleotide sequences which comes to 9 per year for 10 million years and that is twice the amount of time scientists five it.

Try typing mutation rate for Homo sapians and you will confirm what I have allready told you for months. Try the Wikepedia article on the subject of mutations as a primer.

The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but is generally on the order of 10-8 (1 in 100 million) per nucleotide per generation[1]. Specifically, mutation rate in eukaryotes is in general 10-4 to 10-6, and for bacteria and phages the rate is 10-5 to 10-7 per gene per generation[2].

http://en.wikipedia.org/wiki/Mutation_rate

Start with that and we can go from there, I have things to do for now and I don't know how to make it any simplier.

Grace and peace,
Mark

 

[RightWingGirl]

I'm stuggling with this right now. I've read that human dna is 99% similar to the dna of chimps. How do we as creationists reconcile that to our belief that we are not related to apes?

What is there to be reconciled? What does this similarity show? A similarity and nothing else.
Because DNA is, simplistically, the "pattern" for our bodies--a code that describes all of our physical attributes, it should be no surprise that our DNA is similar to apes, because we are physically similar to chimps.

 

[shernren]

O_O

The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but is generally on the order of 10-8 (1 in 100 million) per nucleotide per generation[1]. Specifically, mutation rate in eukaryotes is in general 10-4 to 10-6, and for bacteria and phages the rate is 10-5 to 10-7 per gene per generation[2].

(emphasis added)

The actual rate is:

10^-8 / nucleotide / generation
* 3.2*10^9 base pairs

~= 32 nucleotides per generation.

Does it still seem minute to you?

 

[rmwilliamsll]

O_O



(emphasis added)

The actual rate is:

10^-8 / nucleotide / generation
* 3.2*10^9 base pairs

~= 32 nucleotides per generation.

Does it still seem minute to you?

at 20 years generation time that is close to 1.5 nucleotides per year.
and my back of the envelope calculation above was .5 nucleotides per year would account for the information we've read in the articles cited.

 

[random_guy]

What is there to be reconciled? What does this similarity show? A similarity and nothing else.
Because DNA is, simplistically, the "pattern" for our bodies--a code that describes all of our physical attributes, it should be no surprise that our DNA is similar to apes, because we are physically similar to chimps.

The problem isn't just similarity, it's similarity such that it shows evidence of common descent. For example, HRV give evidence that humans and apes share a common ancestor. In our DNA sequence, there's evidence that supports two ape chromosomes fused into one. Our pseudogene for vitamin C are both similar, even though both a faulty genes. Why would defects, pattern markings, etc... all be in places that we expect according to evolution?

 

[shernren]

And that is why units are very important in science. Often if a student can memorize how the units are inter-derived in physics half the battle is won - 1N = 1kgms^-2 is as concise (although slightly incomplete) a statement of Newton's Second Law as you'll get.

I chose the darwin to measure your data on skull size change because it is an appropriate unit to measure phenotypic divergence when it is difficult or impossible to directly quantify the underlying genetic causes of the divergence. In this case, the divergence is ln(3)/5 ~= 0.2 darwins. This is rather huge when compared to the fossil record, over which the average rate of change is on the order of 0.05 darwins. But modern experiments have observed rates up to 16,000 darwins, so this isn't a problem.

Secondly, in terms of units, the unit solves the problem. 10^-8 mutations per nucleotide per generation has to be multiplied by the length of the human genome, 3.2 x 10^9 base pairs, to get the average expectation of 32 mutations a generation. Also, the unit denotes that we are actually applying a rate for individual nucleotide substitutions, to which the rate for indels has to be added separately. (And an expected indel rate hasn't been supplied. Is 1 indel a year too many?) IOW, the mutation rate only has to apply to the nucleotide divergence, which is 1.06% x 3.2x10^9 = 3.4 million nucleotides.

Applying a normal probability distribution (with mean = np = 32, std. dev. = sqrt(npq) = 5.65685), there is a 98.5% chance that more than 20 mutations will occur per generation. Over a 40-year generational length this is 0.5 nucleotides a year - right up rmswilliams' ballpark estimate.

Taking the figures over 5 million years, the probability of a nucleotide undergoing mutation is 10^-8 mutations per nucleotide per generation x 125,000 generations = 1.25 x 10^-3 mutations per nucleotide. Using another normal distribution (mean = np = 4,000,000, std. dev. = sqrt(npq) = 1999), the probability that less than 3.4 million mutations will occur is ... practically zero.

If you want the mathematical guts of the calculations, come ask me. It's just typical normal distribution calculations, nothing difficult involved.

 

[mark kennedy]

O_O



(emphasis added)

The actual rate is:

10^-8 / nucleotide / generation
* 3.2*10^9 base pairs

~= 32 nucleotides per generation.

Does it still seem minute to you?

You are overlooking the obvious, we are talking about mutations that are fixed in the respective genomes. The human genome diverges about 1/10 of 1% dispite the fact that there are maybe 130 mutations in every human being. For the most part they are neutral and the vast majority of the rest are deleterious.

The fact is 32 nucleotides per 20 year generations isn't even close and that is assuming that they are all fixed genome wide. It would be more like 180 per generation and that is not counting the SNPs and chromosomal rearrangements. You have major chromosomal rearrangements coming to about 20 million nucleotides, 35 million single nucleotide polymorphisms and just under 90 million nucleotides for the indels. Some of these indels are upwards of 70,000 nucleotides long and a single nucleotide substitution can cause mental retardation, sickle cell...etc.

You might want to sharpen your pencil and go back and recalculate this.

Grace and peace,
Mark

 

[shernren]

Well, I'm quite sure I'm wrong to assume that the 10^-8 mutation rate doesn't have to cover indels, so quite a bit of post #31 is probably wrong. I need a geneticist! XD It's 1:30 am, the only reason i'm on is because there's a really good performance of Beethoven's Moonlight Sonata on my classical streaming radio (which just finished). Over the next few days we'll look into this, it should be interesting.

Thanks for providing the source for your 10^-8 figure, Mark, I hope we've cleared up the misunderstanding. Now could I ask, what's your source that the human genome "diverges about 0.1%" - diverges from what? It's alright if you can't remember the exact URL but at least the specific terminology used so that I can Google it up more easily.

Also, I'm still confused about whether you are arguing from the rate of mutation required, or that the energetic costs of the mutations are unfeasible. Statements like this: a single nucleotide substitution can cause mental retardation, sickle cell...etc. seem to indicate that you regard some genomic changes as being unexplainable by evolution no matter what timescale is assigned.

For my part, I will have to check out Wikipedia's sources. In particular, if it is legitimate to use the 10^-6 figure provided as the lower bound for eukaryotes, I end up with a very comfortable mean expectation of 3200 mutations per generation, far higher than you consider necessary. The most important thing to note is that suddenly, our target is less than one order of magnitude from our current data (180 needed vs. 32 actual). If the trend continues, maybe we'll have to start asking why evolution was so slow, not so fast, in the human line.

 

[sfs]

9 nucleotides fixed genome wide, per year, for 10 million years is not gradual, it's impossible.

Mark, I thought you'd agreed to stop using this argument, the last time I corrected you on it. What happened?

The mutation rate is 10^-8, it is not a difficult statistic to find if you make any kind of an effort at all. What is more, well over 98% will be neutral which is to say they do nothing at all with the vast majority of the balance being deleterious which means they are harmfull. We have a great disparity between the known divergance rate which is a decimal point followed by 8 zeros. Then there is the rate of fixed nucleotide sequences which comes to 9 per year for 10 million years and that is twice the amount of time scientists five it.

I don't know what this means, but there is absolutely nothing surprising to geneticists about the divergence between humans and chimpanzees. The single-base mutation rate in humans is estimated to be 2x10^-8/bp/gen, which gives 60 mutations per genome copy per generation. Multiply that by two because humans and chimpanzees each accumulate mutations at the same rate. So we expect ~120 mutations per generation, half in humans and half in chimps.

Now neutral mutations (ones that are neither good nor bad for the individual) fix in the population (that is, reach 100% frequency) at the same rate they occur. (Note that any given mutation only has a tiny probability of fixing, but every individual in the population has his own set of new mutations, so there are a ton of mutations around to fix.) So, based on the known mutation rate, geneticists would expect (and did expect) 120 mutations/generation x 300,000 generations (six million years) = 36 million fixed single base differences between humans and chimps. Divided by the 3 billion bases in the genome, that's a predicted difference of 1.2%. The observed difference is 1.3%. (The number comes from the chimpanzee genome paper.) Pretty stunning success for evolution, I'd say.

That's single-base substitutions. There was no good prediction for indels, because there was no good estimate for the mutation rate, just a rough idea that they occur about one-tenth as often as single base substitutions. Comparison of the human and chimp genomes (in the chimp genome paper, again) shows that the rate of indel differences is about one-fifth the single-base difference, rather than one-tenth. This improves our knowledge of the indel mutation rate, but there is nothing problematic about the improved estimate. So where's the problem?

The last time I saw you talking about this subject, you said you'd stop talking about the neutral mutation rate, because your argument was wrong. Why did you change your mind?

 

[Assyrian]

What is more, well over 98% will be neutral which is to say they do nothing at all with the vast majority of the balance being deleterious which means they are harmfull.

Ok biology is not my area, the question is how are these mutations fixed in the genome. The harmful ones obviously aren't, they are usually gotten rid of. What about the 98% with no reason to be selected, how are they fixed?


We are not given a percentage of how many non neutral are harmful, but lets say 99.9%. That's what? 49,000 harmless mutations to every beneficial one? So you could easily have 49,000 neutral mutations on a chromosome when the beneficial mutations comes along. Doesn't this mean every one of the neutral mutations will also be fixed with the beneficial one on the same chromosome.

 

[mark kennedy]

Mark, I thought you'd agreed to stop using this argument, the last time I corrected you on it. What happened?

I agreed not to use it in my discussions with you. I also reserved the right to bring it up from time to time. It's such a solid line of evidence I really hate to abandon it entirely.

I don't know what this means, but there is absolutely nothing surprising to geneticists about the divergence between humans and chimpanzees. The single-base mutation rate in humans is estimated to be 2x10^-8/bp/gen, which gives 60 mutations per genome copy per generation. Multiply that by two because humans and chimpanzees each accumulate mutations at the same rate. So we expect ~120 mutations per generation, half in humans and half in chimps.

That is pretty supprising for me since most of those mutations are neutral while the majority of the rest are deleterious. The thing is that the human race has populations in the billions and the divergence is 1/10 of 1%. With all these generations producing so many mutations it seems a little odd that they are not changing the respective genomes very much at all.

These are not minor variations in the respective genomes, some of them are as long as 70,000 nucleotides long. We are not just talking about the random mutations you statistic is based on. These are going to have to be fixed genome wide, how this does not create at least some supprise in the mind of scientists is a mystery to me.

Now neutral mutations (ones that are neither good nor bad for the individual) fix in the population (that is, reach 100% frequency) at the same rate they occur. (Note that any given mutation only has a tiny probability of fixing, but every individual in the population has his own set of new mutations, so there are a ton of mutations around to fix.) So, based on the known mutation rate, geneticists would expect (and did expect) 120 mutations/generation x 300,000 generations (six million years) = 36 million fixed single base differences between humans and chimps. Divided by the 3 billion bases in the genome, that's a predicted difference of 1.2%. The observed difference is 1.3%. (The number comes from the chimpanzee genome paper.) Pretty stunning success for evolution, I'd say.

I would agree with that as well were it not for the fact that you completly left out the indels that dwarf the SNPs by a considerable amount. That also leaves out the Chromosomal rearrangements but I am not really too concerned about those. I think that can be explained to some extent but the indels being fixed require at least some line of evidence that demonstrates a directly observed mechanism.

The indels are the real issue here, you seem to address that in the next paragraph. Lets see what we have here.

That's single-base substitutions. There was no good prediction for indels, because there was no good estimate for the mutation rate, just a rough idea that they occur about one-tenth as often as single base substitutions. Comparison of the human and chimp genomes (in the chimp genome paper, again) shows that the rate of indel differences is about one-fifth the single-base difference, rather than one-tenth. This improves our knowledge of the indel mutation rate, but there is nothing problematic about the improved estimate. So where's the problem?

For one thing there are gross structural changes in just over 20% of the protein coding genes in Chromosome 22 alone. What is the problem? The ones that are neutral are of no concern I suppose, at least at this point. What is most important is that with most mutations that have an effect its deleterious. You have indels happening about 1/5 as frequently as single base substitutions. Just out of curiosity what would you expect would be the largerst indel discovered in human genetics? Like I say, I'm just curious and interested to see what you think it might be.

The last time I saw you talking about this subject, you said you'd stop talking about the neutral mutation rate, because your argument was wrong. Why did you change your mind?

I remember the exchange but don't recall agreeing that my argument was wrong. It is still a major problem for TOE in my mind and I have yet to see a demonstrated or directly observed mechanism for fixing the indels on this level.

I really would like to move on from the gross number of mutations throughout the respective genomes. One of the reasons I agreed not to bring it up with you was because I realize you have extensive knowledge of the protein coding genes, regulatory genes...etc. I have very little time for research these days but I would dearly love to see one to one comparisons of particular genes.

At any rate, it is exciting to see you again Professor. It's the opportunity to have these discussions with world class scientists like yourself that keeps me fascinated with this subject.

 

[mark kennedy]

Well, I'm quite sure I'm wrong to assume that the 10^-8 mutation rate doesn't have to cover indels, so quite a bit of post #31 is probably wrong. I need a geneticist! XD It's 1:30 am, the only reason i'm on is because there's a really good performance of Beethoven's Moonlight Sonata on my classical streaming radio (which just finished). Over the next few days we'll look into this, it should be interesting.

If you want a scientist that has extensive knowledge of genetics you really want to read sfs carefully. I don't think it's right to tell you who he is but rest assured he is as capable a scientist as you will find on these boards. Now as far as the mutation rate covering indels, the simple answer is that there is no demonstrated mechanism for either producing or preserving mutations on this scale. I realize your tired so lets move on.

Thanks for providing the source for your 10^-8 figure, Mark, I hope we've cleared up the misunderstanding. Now could I ask, what's your source that the human genome "diverges about 0.1%" - diverges from what? It's alright if you can't remember the exact URL but at least the specific terminology used so that I can Google it up more easily.

The Human Genome Project provided that particular statistic, here is the link to their site.

"Almost all (99.9%) nucleotide bases are exactly the same in all people."

http://www.ornl.gov/sci/techresources/Human_Genome/project/info.shtml

This statement from the Intitial Sequence of the Human Genome paper should be in every biology textbook in the world:

"The rediscovery of Mendel's laws of heredity in the opening weeks of the 20th century1, 2, 3 sparked a scientific quest to understand the nature and content of genetic information that has propelled biology for the last hundred years. The scientific progress made falls naturally into four main phases, corresponding roughly to the four quarters of the century. The first established the cellular basis of heredity: the chromosomes. The second defined the molecular basis of heredity: the DNA double helix. The third unlocked the informational basis of heredity, with the discovery of the biological mechanism by which cells read the information contained in genes and with the invention of the recombinant DNA technologies of cloning and sequencing by which scientists can do the same."

http://www.nature.com/nature/journal/v409/n6822/full/409860a0.html

That is the history of modern genetics in a nutshell from world class scientists who produced a landmark scientific achievment.

Also, I'm still confused about whether you are arguing from the rate of mutation required, or that the energetic costs of the mutations are unfeasible. Statements like this: a single nucleotide substitution can cause mental retardation, sickle cell...etc. seem to indicate that you regard some genomic changes as being unexplainable by evolution no matter what timescale is assigned.

The thing that I am most focused on is Darwinian natural selection. In order for something like a mutation to be preserved there has to be an advantage. With genetic mutations this creates a major problem due to the energetic costs of evolution. The deleterious effects will outweigh the beneficial effects by a considerable amount and rarely provide adaptive traits. When they effect something like a vital organ like the brain the statistic probability of them being preserved must be off the chart. Vast numbers of nucleotides being deleted, inserted and fixed genome wide seems unlikely at best.

Frankly, I see it as an impossiblity and there is no demonstrated or directly observed mechanism for this. Heck, they don't even have a rate to gage the occurance of indels which is the most important difference in the two genomes.

For my part, I will have to check out Wikipedia's sources. In particular, if it is legitimate to use the 10^-6 figure provided as the lower bound for eukaryotes, I end up with a very comfortable mean expectation of 3200 mutations per generation, far higher than you consider necessary. The most important thing to note is that suddenly, our target is less than one order of magnitude from our current data (180 needed vs. 32 actual). If the trend continues, maybe we'll have to start asking why evolution was so slow, not so fast, in the human line.

You have got to be putting me on! 3200 per generation? Where on earth did you get that particular statistic?

 

[mark kennedy]

Ok biology is not my area, the question is how are these mutations fixed in the genome. The harmful ones obviously aren't, they are usually gotten rid of. What about the 98% with no reason to be selected, how are they fixed?

That is a good question and I have no idea how or why they would be fixed. There are plenty of random mutations occuring in the human genome but all humans have 99.9% identical nucleotide sequences. This is the thing, dispite the minute differences between any two humans on earth we can be very different. Want to know how this is happening without changing the nucleotide sequences? There are several mechanisms like recombination of genes and prions that turn certain genes on and off. There are also other things that account for adaptive traits that don't need genetic mutations factored into the equation.

We are not given a percentage of how many non neutral are harmful, but lets say 99.9%. That's what? 49,000 harmless mutations to every beneficial one? So you could easily have 49,000 neutral mutations on a chromosome when the beneficial mutations comes along. Doesn't this mean every one of the neutral mutations will also be fixed with the beneficial one on the same chromosome.

The fixation of mutations like chromosomal rearrangements, SNPs and indels would appear to be random. In other words these things simply happen by chance and natural selection acts on them in some nebulous way in the mind of evolutionists.

There are enormous differences between chimpanzees and humans, for instance, their genome is 10% longer. Their brain is 2 1/2 times smaller. They cannot grip, much less design tools. The parts of the genomes that can be compared are 96% simular and only about 29% identical and the list goes on.

This is what I am getting at, there are scientific reasons for creationism. It is absured that a person is antiscience because they refuse to accept they have a common ancestor with apes. In fact, it makes a lot more sense then accepting that enourmous genetic mutations can be fixed genome wide, like clockwork, for millions of years and then suddenly stop altogether.

 

[shernren]

You have got to be putting me on! 3200 per generation? Where on earth did you get that particular statistic?

Basic math with statements from the Wikipedia article you cited. If I replace the 10^-8 rate for humans with the 10^-6 lower bound rate for eukaryotes cited in the article (since, after all, a human is an eukaryote), then 32 mutations per generation is immediately inflated to 3200 mutations per generation. Which is why I need to track down the citations when I get back to college.

For one thing there are gross structural changes in just over 20% of the protein coding genes in Chromosome 22 alone. What is the problem? The ones that are neutral are of no concern I suppose, at least at this point. What is most important is that with most mutations that have an effect its deleterious. You have indels happening about 1/5 as frequently as single base substitutions. Just out of curiosity what would you expect would be the largerst indel discovered in human genetics? Like I say, I'm just curious and interested to see what you think it might be.

Mutations from the ancestral genome into the current human genome would have been beneficial, so they would have a higher fixation rate compared to the fixation rate of mutations away from the current human genome. On the genomic phase space I see the human genome as an attractor, so it should be no surprise that natural selection fixed mutations towards it very rapidly but can only fix mutations away from it very slowly.

But sfs, am I right to view the human genome as an attractor in the genomic phase space?

The thing that I am most focused on is Darwinian natural selection. In order for something like a mutation to be preserved there has to be an advantage. With genetic mutations this creates a major problem due to the energetic costs of evolution. The deleterious effects will outweigh the beneficial effects by a considerable amount and rarely provide adaptive traits. When they effect something like a vital organ like the brain the statistic probability of them being preserved must be off the chart. Vast numbers of nucleotides being deleted, inserted and fixed genome wide seems unlikely at best.

Are you referring to this?

Starting from 12,164 catalogued disease variants in 1,384 human genes, we identified 16 cases in which the altered sequence in a disease allele matched the chimpanzee sequence, and had plausible support in the literature (Table 7; see also Supplementary Table S43). Upon re-sequencing in seven chimpanzees, 15 cases were confirmed homozygous in all individuals, whereas one (PON1 I102V) appears to be a shared polymorphism (Supplementary Table S44).

In these cases, the mutations would be away from the wild-type chimp disease gene towards the human "normal" gene, and would thus be favourable mutations, thus having a higher likelihood and rate of being fixed, wouldn't they?

The fixation of mutations like chromosomal rearrangements, SNPs and indels would appear to be random. In other words these things simply happen by chance and natural selection acts on them in some nebulous way in the mind of evolutionists.

From Wikipedia on genetic drift:

The lifetime of an allele is governed by the effective population size. In a very small population, only a few generations might be required for genetic drift to result in fixation. In a large population, it would take many more generations. On average, an allele will be fixed in 4Ne generations, where Ne is the effective population size.

The important question to ask is what the effective population of humanity was while these genetic changes were taking place, especially in light of ideas like the Toba catastrophe genetic bottleneck.

 

[sfs]

Ok biology is not my area, the question is how are these mutations fixed in the genome. The harmful ones obviously aren't, they are usually gotten rid of. What about the 98% with no reason to be selected, how are they fixed?

Shernren (sp?) has already given the answer to that: random genetic drift. It's a simple concept, really. Suppose I have a new mutation on one of my two copies of a particular gene. I may pass on that one copy to one of my children (meaning the proportion of the population with the mutation would remain unchanged), but I may also pass on zero copies (if I have no children, or if I don't happen to pass on that copy to any of them) or two, three or more copies (depending on how many kids I've got). So the proportion of the population with any variant changes randomly from generation to generation. That's genetic drift.

Because of drift, every site that has two neutral variants will eventually fix one or the other of them. The probability that a particular variant (allele) will fix is just its current frequency. So a 50/50 variant has equal chance of fixing either allele, while a brand new mutation has a very small chance of fixing. Specifically, if there are N individuals in the population, a new mutation has an initial frequency of 1/(2*N), and a probability of fixing of 1/(2*N).

So what is the rate at which new neutral mutations fix? If the probability of a mutation at a given site is u (the mutation rate we've been talking about), then the rate of mutations at that site in the entire population is 2*N*u, that is, every chromosome in the population has an equal shot at mutating each generation. If the rate at which mutations occur is 2*N*u, and the probability that one new mutation will fix is 1/(2*N), the rate at which new mutations fix is 2*N*u / (2*N) = u. Which is why I said the rate at which neutral mutations fix is just the mutation rate.

We are not given a percentage of how many non neutral are harmful, but lets say 99.9%. That's what? 49,000 harmless mutations to every beneficial one? So you could easily have 49,000 neutral mutations on a chromosome when the beneficial mutations comes along. Doesn't this mean every one of the neutral mutations will also be fixed with the beneficial one on the same chromosome.

I'm not sure how to interpret your numbers, since you start out talking about harmful vs neutral and then switch to beneficial vs neutral. Something like 2-3% of mutations are harmful, and are quickly eliminated by natural selection, and a tiny fraction of the remaining ones are beneficial.

Yes, positive selection on one mutation will move nearby neutral variants to fixation; this is known as a selective sweep. It doesn't operate over a whole chromsome, because chromosomes recombine every generation, so that the new mutation will be found on many chromosomal backgrounds after a few generations. Close to the beneficial mutation, however, recombination is unlikely to occur while the mutation is fixing, and that region will be swept. For example, the ability to digest milk as an adult was selected for in Europeans, around the time cattle were domesticated. The beneficial allele was in a regulatory region near the gene for lactase, and the selective sweep included at least a million base pairs of surrounding sequence. (You might be able to tell that I just finished working on a review paper about natural selection in humans.)