A large study on meat and mortality was published today (Arch Intern Med, 2009, 169: 562-571.) The paper concludes that "Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality." But my careful review of the paper suggests that it is total meat intake rather than color that is important, consistent with my earlier observations on other similar studies.
I sent the following email to the corresponding author:
Dear Dr. Sinha,
I read with great interest your article "meat intake and mortality". I work on epigenetics and the role of diet in cancer. My latest paper here:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003390
From Table 1 of your paper, it is shown that the group (Q5) with the highest red meat intake consumed 119 g/kcal of all meat combined. Can you share the data of total amount of all meat about the group with the highest white meat intake? My estimation based on your reported data for this group is 69 g/kcal.
So, it seems that people who mostly eat white meat consumed about 2 fold less total meat than people who eat red meat.
People with highest intake of white meat have lower risk of death than those with lowest intake, as you reported. But those with low intake of white meat actually consume more red meat and total meat in general (table 1).
Bottom line, your data overall shows a link between total amount of meat and mortality. The color of meat is irrelevant. I have made this observation before on the original papers by Willett linking red meat with colon cancer. see my book chapter in Cancer Epigenetics: http://www.amazon.com/Cancer-Epigenetics-Trygve-Tollefsbol/dp/1420045792/ref=sr_1_1?ie=UTF8&s=books&qid=1226425804&sr=1-1
I wish that you could make a follow up revision and change the conclusion "Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality." to "Higher meat intake were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality."
Sincerely yours,
Shi Huang
Tuesday, March 24, 2009
Sunday, March 15, 2009
The mode and tempo of genome size evolution in eukaryotes
This old paper from 2007 was just brought to my attention by a netter discussing the MGD and the latest Science paper on high mutation rate of small genomes. This 2007 paper shows that large genomes show higher rate of large DNA segment duplications, insertions, rearrangments, etc, so called high rate of genome evolution in large genomes. These events are in fact both genetic and epigenetic, and are in fact stated in my MGD paper as epigenetic. Inserting a gene encoding an epigenetic enzyme is more of an epigenetic event. So, large genomes mainly use DNA indels and rearrangements, rather than point mutations, to adapt and evolve. This is the opposite of small genomes or simple organisms. This is entirely predicted by the MGD that large genomes or complex organisms use mainly epigenetic mechanisms rather than point mutations to evolve. Genetic diversity defined in the MGD paper is about neutral point mutations (some neutral indels may be included as well).
The mode and tempo of genome size evolution in eukaryotes
Matthew J. Oliver1,5, Dmitri Petrov2, David Ackerly3, Paul Falkowski1,4, and Oscar M. Schofield1
+Author Affiliations
1 Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, New Jersey 08901, USA;
2 Department of Biology, Stanford University, Stanford, California 93405, USA;
3 Department of Integrative Biology, University of California Berkeley, Berkeley, California 94720, USA;
4 Department of Geological Sciences, Rutgers University, Piscataway, New Jersey 08854, USA
Abstract
Eukaryotic genome size varies over five orders of magnitude; however, the distribution is strongly skewed toward small values. Genome size is highly correlated to a number of phenotypic traits, suggesting that the relative lack of large genomes in eukaryotes is due to selective removal. Using phylogenetic contrasts, we show that the rate of genome size evolution is proportional to genome size, with the fastest rates occurring in the largest genomes. This trend is evident across the 20 major eukaryotic clades analyzed, indicating that over long time scales, proportional change is the dominant and universal mode of genome-size evolution in eukaryotes. Our results reveal that the evolution of eukaryotic genome size can be described by a simple proportional model of evolution. This model explains the skewed distribution of eukaryotic genome sizes without invoking strong selection against large genomes.
The mode and tempo of genome size evolution in eukaryotes
Matthew J. Oliver1,5, Dmitri Petrov2, David Ackerly3, Paul Falkowski1,4, and Oscar M. Schofield1
+Author Affiliations
1 Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, New Jersey 08901, USA;
2 Department of Biology, Stanford University, Stanford, California 93405, USA;
3 Department of Integrative Biology, University of California Berkeley, Berkeley, California 94720, USA;
4 Department of Geological Sciences, Rutgers University, Piscataway, New Jersey 08854, USA
Abstract
Eukaryotic genome size varies over five orders of magnitude; however, the distribution is strongly skewed toward small values. Genome size is highly correlated to a number of phenotypic traits, suggesting that the relative lack of large genomes in eukaryotes is due to selective removal. Using phylogenetic contrasts, we show that the rate of genome size evolution is proportional to genome size, with the fastest rates occurring in the largest genomes. This trend is evident across the 20 major eukaryotic clades analyzed, indicating that over long time scales, proportional change is the dominant and universal mode of genome-size evolution in eukaryotes. Our results reveal that the evolution of eukaryotic genome size can be described by a simple proportional model of evolution. This model explains the skewed distribution of eukaryotic genome sizes without invoking strong selection against large genomes.
Friday, March 6, 2009
Extremely High Mutation Rate of a Hammerhead Viroid by Gago et al
This Science paper confirms the MGD hypothesis. The author stated: "Such error-prone replication can only be tolerated by extremely simple genomes such as those of viroids." The simpler the organism, the more mutations it can tolerate.
Science 6 March 2009: Vol. 323. no. 5919, p. 1308 DOI: 10.1126/science.1169202 Prev | Table of Contents | Next
BREVIA
Extremely High Mutation Rate of a Hammerhead Viroid
Selma Gago,1 Santiago F. Elena,1 Ricardo Flores,1 Rafael Sanjuán1,2*
The mutation rates of viroids, plant pathogens with minimal non-protein-coding RNA genomes, are unknown. Their replication is mediated by host RNA polymerases and, in some cases, by hammerhead ribozymes, small self-cleaving motifs embedded in the viroid. By using the principle that the population frequency of nonviable genotypes equals the mutation rate, we screened for changes that inactivated the hammerheads of Chrysanthemum chlorotic mottle viroid. We obtained a mutation rate of 1/400 per site, the highest reported for any biological entity. Such error-prone replication can only be tolerated by extremely simple genomes such as those of viroids and, presumably, the primitive replicons of the RNA world. Our results suggest that the emergence of replication fidelity was critical for the evolution of complexity in the early history of life.
Also see this Science comment: "Fast-Mutating Viroids Hold Clues to Early Life" by Carl Zimmer
http://blogs.sciencemag.org/origins/2009/03/fast-mutating-viroids-hold-clu.html
"What's intriguing about this pattern is the size of the genomes involved: The higher the mutation rate, the smaller the genome."
Science 6 March 2009: Vol. 323. no. 5919, p. 1308 DOI: 10.1126/science.1169202 Prev | Table of Contents | Next
BREVIA
Extremely High Mutation Rate of a Hammerhead Viroid
Selma Gago,1 Santiago F. Elena,1 Ricardo Flores,1 Rafael Sanjuán1,2*
The mutation rates of viroids, plant pathogens with minimal non-protein-coding RNA genomes, are unknown. Their replication is mediated by host RNA polymerases and, in some cases, by hammerhead ribozymes, small self-cleaving motifs embedded in the viroid. By using the principle that the population frequency of nonviable genotypes equals the mutation rate, we screened for changes that inactivated the hammerheads of Chrysanthemum chlorotic mottle viroid. We obtained a mutation rate of 1/400 per site, the highest reported for any biological entity. Such error-prone replication can only be tolerated by extremely simple genomes such as those of viroids and, presumably, the primitive replicons of the RNA world. Our results suggest that the emergence of replication fidelity was critical for the evolution of complexity in the early history of life.
Also see this Science comment: "Fast-Mutating Viroids Hold Clues to Early Life" by Carl Zimmer
http://blogs.sciencemag.org/origins/2009/03/fast-mutating-viroids-hold-clu.html
"What's intriguing about this pattern is the size of the genomes involved: The higher the mutation rate, the smaller the genome."
Saturday, January 17, 2009
The DNA-encoded nucleosome organization of a eukaryotic genome by Kaplan et al
This paper supports the MGD hypothesis.
Nature advance online publication 17 December 2008 | doi:10.1038/nature07667; Received 2 October 2008; Accepted 26 November 2008; Published online 17 December 2008
The DNA-encoded nucleosome organization of a eukaryotic genome
Noam Kaplan1,9, Irene K. Moore3,9, Yvonne Fondufe-Mittendorf3, Andrea J. Gossett4, Desiree Tillo5, Yair Field1, Emily M. LeProust6, Timothy R. Hughes5,7,8, Jason D. Lieb4, Jonathan Widom3 & Eran Segal1,2
Department of Computer Science and Applied Mathematics,
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, Illinois 60208, USA
Department of Biology, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Agilent Technologies Inc., Genomics—LSSU, 5301 Stevens Creek Boulevard, MS 3L/MT Santa Clara, California 95051, USA
Terrence Donnelly Centre for Cellular & Biomolecular Research,
Banting and Best Department of Medical Research, 160 College Street, Toronto, Ontario M5S 3E1, Canada
These authors contributed equally to this work.
Correspondence to: Jonathan Widom3Eran Segal1,2 Correspondence and requests for materials should be addressed to J.W. (Email: j-widom@northwestern.edu) or E.S. (Email: eran.segal@weizmann.ac.il).
Nucleosome organization is critical for gene regulation1. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers2, competition with site-specific DNA-binding proteins3, and the DNA sequence preferences of the nucleosomes themselves4, 5, 6, 7, 8. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo 7, 9, 10, 11, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.
Nature advance online publication 17 December 2008 | doi:10.1038/nature07667; Received 2 October 2008; Accepted 26 November 2008; Published online 17 December 2008
The DNA-encoded nucleosome organization of a eukaryotic genome
Noam Kaplan1,9, Irene K. Moore3,9, Yvonne Fondufe-Mittendorf3, Andrea J. Gossett4, Desiree Tillo5, Yair Field1, Emily M. LeProust6, Timothy R. Hughes5,7,8, Jason D. Lieb4, Jonathan Widom3 & Eran Segal1,2
Department of Computer Science and Applied Mathematics,
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, Illinois 60208, USA
Department of Biology, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Agilent Technologies Inc., Genomics—LSSU, 5301 Stevens Creek Boulevard, MS 3L/MT Santa Clara, California 95051, USA
Terrence Donnelly Centre for Cellular & Biomolecular Research,
Banting and Best Department of Medical Research, 160 College Street, Toronto, Ontario M5S 3E1, Canada
These authors contributed equally to this work.
Correspondence to: Jonathan Widom3Eran Segal1,2 Correspondence and requests for materials should be addressed to J.W. (Email: j-widom@northwestern.edu) or E.S. (Email: eran.segal@weizmann.ac.il).
Nucleosome organization is critical for gene regulation1. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers2, competition with site-specific DNA-binding proteins3, and the DNA sequence preferences of the nucleosomes themselves4, 5, 6, 7, 8. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo 7, 9, 10, 11, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.
Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites by Sasaki et al
The paper by Sasaki et al in Science supports the MGD hypothesis. Indel rate is inversely related to point mutation rate. Indel is more of an epigenetic event.
Originally published in Science Express on 11 December 2008
Science 16 January 2009:
Vol. 323. no. 5912, pp. 401 - 404
DOI: 10.1126/science.1163183
Prev | Table of Contents | Next
REPORTS
Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites
Shin Sasaki,1* Cecilia C. Mello,2 Atsuko Shimada,3 Yoichiro Nakatani,1 Shin-ichi Hashimoto,4 Masako Ogawa,4 Kouji Matsushima,4 Sam Guoping Gu,2 Masahiro Kasahara,1 Budrul Ahsan,1 Atsushi Sasaki,1 Taro Saito,1 Yutaka Suzuki,5 Sumio Sugano,5 Yuji Kohara,6 Hiroyuki Takeda,3 Andrew Fire,2 Shinichi Morishita1,7
Might DNA sequence variation reflect germline genetic activity and underlying chromatin structure? We investigated this question using medaka (Japanese killifish, Oryzias latipes), by comparing the genomic sequences of two strains (Hd-rR and HNI) and by mapping 37.3 million nucleosome cores from Hd-rR blastulae and 11,654 representative transcription start sites from six embryonic stages. We observed a distinctive 200–base pair (bp) periodic pattern of genetic variation downstream of transcription start sites; the rate of insertions and deletions longer than 1 bp peaked at positions of approximately +200, +400, and +600 bp, whereas the point mutation rate showed corresponding valleys. This 200-bp periodicity was correlated with the chromatin structure, with nucleosome occupancy minimized at positions 0, +200, +400, and +600 bp. These data exemplify the potential for genetic activity (transcription) and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.
Originally published in Science Express on 11 December 2008
Science 16 January 2009:
Vol. 323. no. 5912, pp. 401 - 404
DOI: 10.1126/science.1163183
Prev | Table of Contents | Next
REPORTS
Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites
Shin Sasaki,1* Cecilia C. Mello,2 Atsuko Shimada,3 Yoichiro Nakatani,1 Shin-ichi Hashimoto,4 Masako Ogawa,4 Kouji Matsushima,4 Sam Guoping Gu,2 Masahiro Kasahara,1 Budrul Ahsan,1 Atsushi Sasaki,1 Taro Saito,1 Yutaka Suzuki,5 Sumio Sugano,5 Yuji Kohara,6 Hiroyuki Takeda,3 Andrew Fire,2 Shinichi Morishita1,7
Might DNA sequence variation reflect germline genetic activity and underlying chromatin structure? We investigated this question using medaka (Japanese killifish, Oryzias latipes), by comparing the genomic sequences of two strains (Hd-rR and HNI) and by mapping 37.3 million nucleosome cores from Hd-rR blastulae and 11,654 representative transcription start sites from six embryonic stages. We observed a distinctive 200–base pair (bp) periodic pattern of genetic variation downstream of transcription start sites; the rate of insertions and deletions longer than 1 bp peaked at positions of approximately +200, +400, and +600 bp, whereas the point mutation rate showed corresponding valleys. This 200-bp periodicity was correlated with the chromatin structure, with nucleosome occupancy minimized at positions 0, +200, +400, and +600 bp. These data exemplify the potential for genetic activity (transcription) and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.
Sunday, December 28, 2008
Dr. Francisco Ayala's response and my rebuttal
I posted the following on Amazon.com, http://www.amazon.com/review/R8WB8ZQSOUVGC
In case anyone is interested in what the NAS experts may respond to my email to them, I here make public the response from NAS member Dr. Francisco Ayala who headed the NAS panel that wrote the booklet. I also post here my rebuttal. I have yet to hear from Dr. Ayala again after my rebuttal of 11/18/2008, suggesting that he is no longer willing to engage in this exchange and in persuading me to his view. All I know is that if I have the truth, I would be very generous with my time to relentlessly persuade every honest truth seeker in the world to my view, even if I have to do it individual by individual.
Since these email exchanges are purely scientific in nature, I see no reason why they cannot be made public. Dr. Ayala is a very public person anyway and has in my view taught false information, perhaps unknowingly, to my children and millions of others', and should therefore be made publicly accountable for his views. But I have deleted any personal information such as email address. If this public exposure could stimulate anyone to debate me in public with the aim of seeking truth and teaching only truth to our children, I would indeed be very pleased. The well known policy of the Darwinian mainstream to not to engage in debate with competing parties is not conductive to seeking truth and is a pure sign of weakness.
Date: Fri, 14 Nov 2008 11:15:03 -0800
To: "Labov, Jay"
From: "Francisco J. Ayala" < email address deleted >
Subject: RE: evolution teaching
Cc: Shi Huang < email address deleted >
Dear Jay:
Our statements are correct as they stand, but of course we don't explain everything that can be said about the subject, including apparent and real variations around the expected average values in molecular and other differences. Perhaps Dr. Huang might be willing to read one of my numerous papers concerning the vagaries of the molecular clock, showing that the rate of molecular evolution is not stochastically constant (as predicted by the neutral theory of molecular evolution) and that it varies from gene to gene and from group to group of organisms, which does not invalidate the statements we make in the booklet, neither in the 1999 or in the 2005 versions. Would Dr. Huang consider invalid the statement that people who have a healthy diet and exercise live longer than those who don't, just because some people who do, die younger than some people who don't?
Two papers, among many, that Dr. Huang might want to read are:
-F.J. Ayala, "On the virtues and pitfalls of the molecular evolutionary clock," The Wilhelmine E. Key Award lecture of the American Genetics Association, J. of Heredity 77:226-235, 1986.
-F.J. Ayala, "Vagaries of the molecular clock," PNAS 94:7776-7783, 1997.
Best wishes,
Francisco
P.S. I find it nothing short of amusing to read Dr. Huang's statement that "The experts [who prepared the NAS booklet] simply have not understood molecular evolution well enough to teach it." As you may know, over the years I have published in top journals well over 100 papers on molecular evolution (and edited a book with that title as early as 1976).
Date: Fri, 18 Nov 2008 4:04 -0800
To: "Francisco J. Ayala" < email address deleted >
From: Shi Huang < email address deleted >
Subject: RE: evolution teaching
Cc: "Labov, Jay" < email address deleted>
Dear Dr. Ayala,
Thank you very much for the comment and the papers. I appreciate very much as it helps me see where you are coming from in believing what you do. I now see that you are an honest true believer of what you do. The only way for an honest person to believe in an incoherent theory is to rationalize the contradictions in a mistaken way, which is what has unfortunately happened to most people in the molecular evolution field. People who are honest and did not happen to make a logical lapse have only one way to go, leaving the field, which is what happened to one of my college classmates after doing her graduate work on molecular evolution in Japan. She found contradictions that she could not resolve and have since held a very low regard of the field. In the recent 25 year reunion, she advised me not to touch this field but I told her that I have sorted it all out. Just an example of the absurd state of affairs in this field, experts could not even agree on whether the molecular clock is a hypothesis or a fact. Your papers show that you consider it a hypothesis. But professor Chung-I Wu of University of Chicago insisted to me that it is a fact not a hypothesis, when I met him this summer in Beijing.
Indeed, the early death of a specific individual who eat healthy diet and exercise in no way contradicts the statement that people who have a healthy diet and exercise live longer than those who don't. The reason is obvious to everyone with a common sense. The statement is of course a statistical average of a population and has no predictive value when applied to any specific individual. Now, if the statement "If two species have a relatively recent common ancestor, their DNA sequences will be more similar than the DNA sequences for two species that share a distant common ancestor" is a statistical average of many splits, then it would have no predictive value to any specific splitting event. If on average, two species have 5% difference in DNA sequence after 25 million years of divergence, it could mean that some species may differ from another by 10% and some by 1%. Therefore when we see a chimp differing from human by 1%, we cannot conclude a split time of 5 million years. And yet that is precisely what has been done by the field. So, Dr. Ayala, if you want your statement to represent a statistical average that would perhaps accommodate the contradictions in your way, you have invalidated the whole molecular evolution field and most of your own work in this area. If even leaders like you would have to make this kind of logical lapses in order to justify a belief in the present theory, could anyone have any confidence in the theory?
I dont know how you got yourself into believing this but I bet it is a personal belief not widely shared by your colleagues. For the statement to be applicable in specific cases, it simply cannot be a statistical average. As far as I know no one else would consider that statement to mean what you have meant. For example, the 1969 PNAS paper by Wilson and Sarich used monkey-human divergence as calibration to date the human-chimp divergence time. Here, the monkey human data is definitely not an average.
Furthermore, there is nothing in the context of the booklet that would inform the readers that the statement means "on average". If it is about the average, then it has no use as a tool of molecular phylogeny and adds nothing useful to evolution studies or in terms of providing evidence to evolution. The fact that it is used by the field for molecular phylogeny studies of specific splitting event shows that it is not about average. If it is not about average, then it is contradicted by about half of all data. In either case, the statement as it stands is misleading and needs to be deleted from the booklet.
Another common way of making peace with a flawed theory is to overlook the contradicting facts as if they never existed. The most earth-shaking and conspicuous fact of molecular evolution that should be taught to everyone and should be the highlight of your booklet is the genetic equidistance result first reported by Margoliash in 1963. This result shows all descendants of yeast are approximately equidistant to yeasts, or more generally, sister species are approximately equidistant to a simpler outgroup. This is the most direct evidence for a constant clock and directly triggered the clock hypothesis. This result is extremely robust and universal. And yet greater than 99% of biologist dont know about it and I rediscovered it independently a few years ago. I was shocked by it, which was in part how I end up doing so much research in the molecular evolution area. The constant mutation rate interpretation of this result makes no sense to me and I want to find my own interpretation and I have now succeeded. This paper (http://precedings.nature.com/documents/1733/version/2) discusses the fallacy of the clock interpretation of the equidistance result. The paper here (http://precedings.nature.com/documents/1751/version/1) provides the real interpretation.
In your paper of 1986 that you sent me, you showed nicely that SOD does not have a constant clock and is therefore unlike CytC. But did you realize that the same data set reported in your paper can also lead me or anyone else to conclude that SOD has a perfectly constant clock, thus in direct contradiction to your conclusion. Data in table 4 shows that yeast is approximately equidistant (69-63 changes) to human, rat, horse, cow, fish, and fly. But you made no mention of this fact that shows that human, rat, horse, cow, fish, and fly all have similar mutation rate. I dont know why the field would let this kinds of contradiction go unnoticed for years. Your paper is not the only one of this kind. The Fitch and Margoliash 1967 Science paper is another that concludes non-equidistance of cytC while never mentioning the other side of their data that shows equidistance.
To falsify the constant mutation rate interpretation of the genetic equidistance result, you can ask your students to do this exercise. Use a complex organism such as human as the outgroup to compare with sister species from a simpler clade such as mollusks or the reptile/birds clade. You will find that octopus is closer to human than cockle is, or birds are closer to human than snakes are. But the constant mutation rate hypothesis would predict equidistance, regardless whether the outgroup is more or less complex. If you read my paper, you will find why the complexity of the outgroup makes a huge difference on the equidistance result.
If you read these papers of mine, you will find a completely different interpretation of all the major facts of molecular evolution. It is coherent and has no contradictions. I have no doubt that it is the correct and true story of nature. This is why I said that the experts have not really understood molecular evolution. I do not mean to be disrespectful and I value greatly the primary data generated by these experts. It is the interpretation that is in question. I realize that pointing out contradictions is no way of changing minds. The only way is offer your own theory as a target of attack by your opponents or competing parties. So please feel free to attack it anyway you wish. Real gold is not afraid of burning by fire (Chinese proverb).
I wish I have expressed my ideas clearly so that you have no need to spend time in getting back to me with questions. But I am always at your service if you would find it helpful. If my ideas are sound to you, I wish you would consider revising the booklet. If you can find flaws in my ideas, please offer your rebuttal.
Best regards,
Shi
In case anyone is interested in what the NAS experts may respond to my email to them, I here make public the response from NAS member Dr. Francisco Ayala who headed the NAS panel that wrote the booklet. I also post here my rebuttal. I have yet to hear from Dr. Ayala again after my rebuttal of 11/18/2008, suggesting that he is no longer willing to engage in this exchange and in persuading me to his view. All I know is that if I have the truth, I would be very generous with my time to relentlessly persuade every honest truth seeker in the world to my view, even if I have to do it individual by individual.
Since these email exchanges are purely scientific in nature, I see no reason why they cannot be made public. Dr. Ayala is a very public person anyway and has in my view taught false information, perhaps unknowingly, to my children and millions of others', and should therefore be made publicly accountable for his views. But I have deleted any personal information such as email address. If this public exposure could stimulate anyone to debate me in public with the aim of seeking truth and teaching only truth to our children, I would indeed be very pleased. The well known policy of the Darwinian mainstream to not to engage in debate with competing parties is not conductive to seeking truth and is a pure sign of weakness.
Date: Fri, 14 Nov 2008 11:15:03 -0800
To: "Labov, Jay"
From: "Francisco J. Ayala" < email address deleted >
Subject: RE: evolution teaching
Cc: Shi Huang < email address deleted >
Dear Jay:
Our statements are correct as they stand, but of course we don't explain everything that can be said about the subject, including apparent and real variations around the expected average values in molecular and other differences. Perhaps Dr. Huang might be willing to read one of my numerous papers concerning the vagaries of the molecular clock, showing that the rate of molecular evolution is not stochastically constant (as predicted by the neutral theory of molecular evolution) and that it varies from gene to gene and from group to group of organisms, which does not invalidate the statements we make in the booklet, neither in the 1999 or in the 2005 versions. Would Dr. Huang consider invalid the statement that people who have a healthy diet and exercise live longer than those who don't, just because some people who do, die younger than some people who don't?
Two papers, among many, that Dr. Huang might want to read are:
-F.J. Ayala, "On the virtues and pitfalls of the molecular evolutionary clock," The Wilhelmine E. Key Award lecture of the American Genetics Association, J. of Heredity 77:226-235, 1986.
-F.J. Ayala, "Vagaries of the molecular clock," PNAS 94:7776-7783, 1997.
Best wishes,
Francisco
P.S. I find it nothing short of amusing to read Dr. Huang's statement that "The experts [who prepared the NAS booklet] simply have not understood molecular evolution well enough to teach it." As you may know, over the years I have published in top journals well over 100 papers on molecular evolution (and edited a book with that title as early as 1976).
Date: Fri, 18 Nov 2008 4:04 -0800
To: "Francisco J. Ayala" < email address deleted >
From: Shi Huang < email address deleted >
Subject: RE: evolution teaching
Cc: "Labov, Jay" < email address deleted>
Dear Dr. Ayala,
Thank you very much for the comment and the papers. I appreciate very much as it helps me see where you are coming from in believing what you do. I now see that you are an honest true believer of what you do. The only way for an honest person to believe in an incoherent theory is to rationalize the contradictions in a mistaken way, which is what has unfortunately happened to most people in the molecular evolution field. People who are honest and did not happen to make a logical lapse have only one way to go, leaving the field, which is what happened to one of my college classmates after doing her graduate work on molecular evolution in Japan. She found contradictions that she could not resolve and have since held a very low regard of the field. In the recent 25 year reunion, she advised me not to touch this field but I told her that I have sorted it all out. Just an example of the absurd state of affairs in this field, experts could not even agree on whether the molecular clock is a hypothesis or a fact. Your papers show that you consider it a hypothesis. But professor Chung-I Wu of University of Chicago insisted to me that it is a fact not a hypothesis, when I met him this summer in Beijing.
Indeed, the early death of a specific individual who eat healthy diet and exercise in no way contradicts the statement that people who have a healthy diet and exercise live longer than those who don't. The reason is obvious to everyone with a common sense. The statement is of course a statistical average of a population and has no predictive value when applied to any specific individual. Now, if the statement "If two species have a relatively recent common ancestor, their DNA sequences will be more similar than the DNA sequences for two species that share a distant common ancestor" is a statistical average of many splits, then it would have no predictive value to any specific splitting event. If on average, two species have 5% difference in DNA sequence after 25 million years of divergence, it could mean that some species may differ from another by 10% and some by 1%. Therefore when we see a chimp differing from human by 1%, we cannot conclude a split time of 5 million years. And yet that is precisely what has been done by the field. So, Dr. Ayala, if you want your statement to represent a statistical average that would perhaps accommodate the contradictions in your way, you have invalidated the whole molecular evolution field and most of your own work in this area. If even leaders like you would have to make this kind of logical lapses in order to justify a belief in the present theory, could anyone have any confidence in the theory?
I dont know how you got yourself into believing this but I bet it is a personal belief not widely shared by your colleagues. For the statement to be applicable in specific cases, it simply cannot be a statistical average. As far as I know no one else would consider that statement to mean what you have meant. For example, the 1969 PNAS paper by Wilson and Sarich used monkey-human divergence as calibration to date the human-chimp divergence time. Here, the monkey human data is definitely not an average.
Furthermore, there is nothing in the context of the booklet that would inform the readers that the statement means "on average". If it is about the average, then it has no use as a tool of molecular phylogeny and adds nothing useful to evolution studies or in terms of providing evidence to evolution. The fact that it is used by the field for molecular phylogeny studies of specific splitting event shows that it is not about average. If it is not about average, then it is contradicted by about half of all data. In either case, the statement as it stands is misleading and needs to be deleted from the booklet.
Another common way of making peace with a flawed theory is to overlook the contradicting facts as if they never existed. The most earth-shaking and conspicuous fact of molecular evolution that should be taught to everyone and should be the highlight of your booklet is the genetic equidistance result first reported by Margoliash in 1963. This result shows all descendants of yeast are approximately equidistant to yeasts, or more generally, sister species are approximately equidistant to a simpler outgroup. This is the most direct evidence for a constant clock and directly triggered the clock hypothesis. This result is extremely robust and universal. And yet greater than 99% of biologist dont know about it and I rediscovered it independently a few years ago. I was shocked by it, which was in part how I end up doing so much research in the molecular evolution area. The constant mutation rate interpretation of this result makes no sense to me and I want to find my own interpretation and I have now succeeded. This paper (http://precedings.nature.com/documents/1733/version/2) discusses the fallacy of the clock interpretation of the equidistance result. The paper here (http://precedings.nature.com/documents/1751/version/1) provides the real interpretation.
In your paper of 1986 that you sent me, you showed nicely that SOD does not have a constant clock and is therefore unlike CytC. But did you realize that the same data set reported in your paper can also lead me or anyone else to conclude that SOD has a perfectly constant clock, thus in direct contradiction to your conclusion. Data in table 4 shows that yeast is approximately equidistant (69-63 changes) to human, rat, horse, cow, fish, and fly. But you made no mention of this fact that shows that human, rat, horse, cow, fish, and fly all have similar mutation rate. I dont know why the field would let this kinds of contradiction go unnoticed for years. Your paper is not the only one of this kind. The Fitch and Margoliash 1967 Science paper is another that concludes non-equidistance of cytC while never mentioning the other side of their data that shows equidistance.
To falsify the constant mutation rate interpretation of the genetic equidistance result, you can ask your students to do this exercise. Use a complex organism such as human as the outgroup to compare with sister species from a simpler clade such as mollusks or the reptile/birds clade. You will find that octopus is closer to human than cockle is, or birds are closer to human than snakes are. But the constant mutation rate hypothesis would predict equidistance, regardless whether the outgroup is more or less complex. If you read my paper, you will find why the complexity of the outgroup makes a huge difference on the equidistance result.
If you read these papers of mine, you will find a completely different interpretation of all the major facts of molecular evolution. It is coherent and has no contradictions. I have no doubt that it is the correct and true story of nature. This is why I said that the experts have not really understood molecular evolution. I do not mean to be disrespectful and I value greatly the primary data generated by these experts. It is the interpretation that is in question. I realize that pointing out contradictions is no way of changing minds. The only way is offer your own theory as a target of attack by your opponents or competing parties. So please feel free to attack it anyway you wish. Real gold is not afraid of burning by fire (Chinese proverb).
I wish I have expressed my ideas clearly so that you have no need to spend time in getting back to me with questions. But I am always at your service if you would find it helpful. If my ideas are sound to you, I wish you would consider revising the booklet. If you can find flaws in my ideas, please offer your rebuttal.
Best regards,
Shi
Tuesday, November 11, 2008
Misleading teachings in “Science, Evolution, and Creationism, A view from the National Academy of Sciences, 2008”
Today I sent an email to Jay Labov, cc. Francisco Ayala, of the National Academy of Sciences, asking them to correct a misleading statement on molecular evolution.
Dear Jay:
I find it sad that a group of scientists of the NAS caliber simply cannot make a true statement in the field of molecular evolution.
I have written to you in 2005 about a misleading (part truth part lie) statement in the 1999 booklet 'Science and Creationism, A view from the National Academy of Sciences, 1999.' This statement is: “The more closely related two organisms are, the less different their DNA will be.” The reality is that vastly different species differ little in DNA and similar species differ vastly in DNA. Hippos should be more related to pigs in morphology, but hippos are more related to whales in DNA/protein than to pigs. Crocodiles are similar to lizards in phenotypes but are more related to birds in DNA/protein. The variation in brain power and gross phenotype between human and chimpanzee is much greater than between the mouse species Mus musculus and Mus spretus, although the sequence difference in the two cases is similar.
I am glad to see that the expert panel has now deleted this misleading statement in the 2008 edition “Science, Evolution, and Creationism, A view from the National Academy of Sciences, 2008”. But I am also sad to see that they again made a misleading statement that is part truth part lie. This statement is : “If two species have a relatively recent common ancestor, their DNA sequences will be more similar than the DNA sequences for two species that share a distant common ancestor.”
Here are just three examples of the factual contradictions to this statement. Two different mice strains that separated no more than 12 million years ago had more dissimilarity in DNA than human and monkey that shared a common ancestor 20-30 million years ago. (see Xiang et al., Human Molecular Genetics. 17(1):27-37, 2008.) At the DNA sequence level, Apodemus and Mus differ by 18% as estimated from neutral sites of genes. In comparison, genome divergence is 8% between human and the Old World monkeys. Two madaka fish populations that separated 4 million years ago had more dissimilarity in DNA than human and chimpanzees that separated 5-7 million years ago. (see Nature, 447:714-719, 2007, June 7). Two flowering plants (Arabidopsis and apple tree) that shared a common ancestor no more than 125 million years ago have more dissimilarity in DNA than humans and birds that shared a common ancestor 310 million years ago. (see my paper, submitted, preprint available at http://precedings.nature.com/documents/1733/version/2)
Why cannot the experts just make a truthful statement that has no factual contradictions? I have given the question some thoughts. My answer is simple. The experts simply have not understood molecular evolution well enough to be able to teach it.
Please make a quick revision to your booklet, deleting the part on molecular evolution. After repeated tries, the experts have shown that they are incapable of stating truth without also stating lies. The only way out is to say nothing on something you don't really understand.
Yours truly,
Shi Huang
Dear Jay:
I find it sad that a group of scientists of the NAS caliber simply cannot make a true statement in the field of molecular evolution.
I have written to you in 2005 about a misleading (part truth part lie) statement in the 1999 booklet 'Science and Creationism, A view from the National Academy of Sciences, 1999.' This statement is: “The more closely related two organisms are, the less different their DNA will be.” The reality is that vastly different species differ little in DNA and similar species differ vastly in DNA. Hippos should be more related to pigs in morphology, but hippos are more related to whales in DNA/protein than to pigs. Crocodiles are similar to lizards in phenotypes but are more related to birds in DNA/protein. The variation in brain power and gross phenotype between human and chimpanzee is much greater than between the mouse species Mus musculus and Mus spretus, although the sequence difference in the two cases is similar.
I am glad to see that the expert panel has now deleted this misleading statement in the 2008 edition “Science, Evolution, and Creationism, A view from the National Academy of Sciences, 2008”. But I am also sad to see that they again made a misleading statement that is part truth part lie. This statement is : “If two species have a relatively recent common ancestor, their DNA sequences will be more similar than the DNA sequences for two species that share a distant common ancestor.”
Here are just three examples of the factual contradictions to this statement. Two different mice strains that separated no more than 12 million years ago had more dissimilarity in DNA than human and monkey that shared a common ancestor 20-30 million years ago. (see Xiang et al., Human Molecular Genetics. 17(1):27-37, 2008.) At the DNA sequence level, Apodemus and Mus differ by 18% as estimated from neutral sites of genes. In comparison, genome divergence is 8% between human and the Old World monkeys. Two madaka fish populations that separated 4 million years ago had more dissimilarity in DNA than human and chimpanzees that separated 5-7 million years ago. (see Nature, 447:714-719, 2007, June 7). Two flowering plants (Arabidopsis and apple tree) that shared a common ancestor no more than 125 million years ago have more dissimilarity in DNA than humans and birds that shared a common ancestor 310 million years ago. (see my paper, submitted, preprint available at http://precedings.nature.com/documents/1733/version/2)
Why cannot the experts just make a truthful statement that has no factual contradictions? I have given the question some thoughts. My answer is simple. The experts simply have not understood molecular evolution well enough to be able to teach it.
Please make a quick revision to your booklet, deleting the part on molecular evolution. After repeated tries, the experts have shown that they are incapable of stating truth without also stating lies. The only way out is to say nothing on something you don't really understand.
Yours truly,
Shi Huang
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