Molecular gene (genome) concept scientifically untenable

[PAWahid]

For nearly six decades now, biologists have been promoting molecular gene (DNA) as the blueprint of life. The world now believes that it is a chemical molecule that decides the phenotype, development, heritable traits and behaviour of an organism. Last century has been famously called ‘the century of the gene’. The molecular gene was born, christened, and brought up during that period.

In 1865, the Austrian monk Johann Gregor Mendel proposed three laws governing heredity, which however did not see light of the day until after 30 years when in 1900 three botanists independently and almost simultaneously rediscovered them. Bateson coined the term “genetics” for the then emerging science of heredity in 1906. Subsequently in 1909, Danish botanist Wilhelm Johannsen introduced the notions of “genotype” and “phenotype”. In addition, he proposed the term “gene” for the elements of the genotype. Johannsen had reservations with respect to gene’s particulate nature and had also warned against assuming genes for a particular character [1]. Thus the gene remained a hypothetical nonphysical entity.

Thomas Hunt Morgan and his group contributed substantially to the understanding of the mechanism of heredity. In the year 1933, on the occasion of his Nobel address, Morgan observed: “At the level at which the genetic experiments lie it does not make the slightest difference whether the gene is a hypothetical unit, or whether the gene is a material particle.” [2]. Nevertheless, many geneticists like Herman J. Muller (Morgan’s student), believed that genes had to be material particles. In 1950, on the occasion of the fiftieth anniversary of the rediscovery of Mendel’s work, Muller however admitted: “[T]he real core of gene theory still appears to lie in the deep unknown. That is, we have as yet no actual knowledge of the mechanism underlying that unique property which makes a gene a gene… its ability to cause the synthesis of another structure like itself, [in] which even the mutations of the original gene are copied. [We] do not know of such things yet in chemistry.” [3].

It has been known since about 1913 that the individual active units of heredity – the genes – are strung together in one-dimensional array along the chromosomes, the threadlike bodies in the nucleus of the cell. George Beadle and Edward Tatum during the late 1930s and early 1940s established the connection between genes and metabolism. They proposed the “one gene, one enzyme hypothesis”. Since chemical reactions occurring in the body are mediated by enzymes, and since enzymes are proteins and thus heritable traits, it is supposed that the gene and proteins are related. These views of gene function strengthened the idea of genetic specificity leading to molecularization of the gene. In the early 1940s, Oswald Avery and his colleagues purified the deoxyribonuleic acid (DNA) of one strain of bacteria, and demonstrated that it was able to transmit the infectious characteristics of that strain to another, harmless one [4]. The elucidation of the structure of DNA as macromolecular double helix by Francis Crick and James Watson in 1953 and in vitro characterization of the process of protein biosynthesis led to the idea that it was the linear sequence of ribonucleic acid derived from one of the DNA strands that directed the synthesis of a linear sequence of amino acids, or a polypeptide, and that this process was mediated by an adaptor molecule (RNA template). In 1958 Francis Crick formulated the “sequence hypothesis” (triplet code or codon, i.e., three bases at a time specified one amino acid) and the “central dogma” of molecular biology. All these considerations ultimately led to defining the molecular gene. According to the classical molecular concept, a gene is a stretch of DNA that encodes a functional product, a single polypeptide chain or RNA molecule. The entire collection of genes encoded by a particular organism is the “genome” that is supposed to constitute the genetic program. The assumption of “one gene, one protein” makes the genes generally synonymous with proteins. Thus the term “gene” refers to the gene that codes for protein. Johannsen’s non-particulate gene thus metamorphosed into particulate gene. The molecular gene was born!

With the introduction of the molecular gene concept, an organism is treated as just a material. It is nothing but a bundle of chemical structures without any nonphysical component.

Molecular biology opened the floodgates of boundless optimism about the ability of the super molecule DNA to decipher the mechanism of life as well as the potential of gene for genetic manipulation. In his classic and influential textbook, The Molecular Biology of the Gene, James Watson stated: “We have complete confidence that further research of the intensity given to genetics will eventually provide man with the ability to describe with completeness the essential features that constitute life.” [5]. But he was grossly wrong. Peter Cook reflects: “Watson and Crick must have thought that the sequence was everything. But life is much more complicated than that.” [6].

Today biology is drifting in the ocean of genomics like a ship that has lost its direction. The gene remains undefined and obscure to say the least. Further the warnings of Johannsen (i.e., against particulate nature of the gene and against considering gene for particular character) have also been proven true.

Molecular gene (genome) concept is wrong

In nature we find two kinds of components, the nonliving and living systems. The nonliving components carry chemical information encoded by their structures, which confers them their characteristic properties and behaviour. The living components carry biological information (or the so-called genetic information), which determines their biological behaviour. It is this biological information, which Wilhelm Johannsen considered as nonphysical while proposing the gene concept and later rejected by the scientific community in favour of a material gene – the DNA molecule.

Genome (DNA) is a chemical molecule. It has physical and chemical properties. By recognizing the gene as material, biologists are superimposing biological information over the chemical information encoded by the chemical structure of DNA. Even if it is taken for granted, it should conform to the well-established chemical fundamentals. By this canon biological information encoded by the genome should be specific to the structure. But in reality, the genome defies this principle in a variety of ways.

a) Changes in the phenotype during ontogenetic development and post-development stage of an individual reflect continuous change of information content of the genome (originally carried in the zygote) with time. A genome can even create two different biosystems (e.g., larva and butterfly)!

How can a molecule (i.e., genome in the zygote) encode information that changes with time?

If biological information can be encoded by the chemical molecule DNA, why no other molecule exhibits this property? Is it not strange that there is only one molecule (DNA) in the whole universe that can encode genetic information?

b) DNA is supposed to encode only information required for protein synthesis. Accordingly, protein-coding DNA is recognized as ‘the gene’. Protein synthesis is not the whole story of “life”. An organism requires information for the synthesis of numerous other substances during its life, development of body structures and their functions, behaviour, instincts, etc. The members of Homo sapiens also have intelligence, consciousness, feelings and freewill.

How can DNA encode genetic information required for instincts, feelings, likes and dislikes, etc.? Do biologists think protein is the sole basis of life?

c) It has been observed that an overwhelming 95% of DNA consists of non-coding DNA in eukaryotes and about 5% is constituted by the coding-DNA (or the genes). The non-coding DNA (ncDNA) is referred to as “junk DNA”. Though structurally comparable to coding DNA, surprisingly, the so-called junk DNA does not encode identical biological information (or vice versa).

How can this be explained?

d) It is believed that mitosis produces daughter cells with identical genome.

If the genomes of the cells in a body are identical, all the cells should carry identical information. But we find the tissues are structurally and functionally different. How can the tissues with identical genome (biological information) exhibit variable structure and function?

e) Recently, it has been shown that the genomes of different tissues are not identical [7]. This discovery sprang from an investigation into the underlying genetic causes of abdominal aortic aneurysms (AAA). The researchers found major genetic differences between blood cells and tissue cells of the same individuals. The finding calls into question one of the most basic assumptions of human genetics that DNA in every cell in the body is identical to every other cell. Apart from that, “This discovery may undercut the rationale behind numerous large-scale genetic studies conducted over the last 15 years, studies which were supposed to isolate the causes of scores of human diseases. Except for cancer, samples of diseased tissue are difficult or even impossible to take from living patients. Thus, the vast majority of genetic samples used in large-scale studies come in the form of blood. However, if it turns out that blood and tissue cells do not match genetically, these ambitious and expensive genome-wide association studies may prove to have been essentially flawed from the outset.” [8].

How is it possible for the genome of a parent cell (e.g., zygote) to create different genomes in the daughter cells? Is it not a clear proof that the genome does not constitute the biological program? Is this not enough of a proof to indicate that genetic information of the organism exists independently of the genome structure and it is according to that, cell structures including genome are produced?

f) Studies at the molecular level fail to demonstrate the expected correspondence between genome and phenotype. The most spectacular example of this is the morphological dissimilarity between human being and chimpanzee despite a 98.7% similarity in their DNA [9]. Although evolutionary biologists speak of genomes of chimp and man as being almost identical to support of their argument of human evolution from an animal, and for establishing chimpanzee as the closest animal ancestor of human being, they have not enumerated so far the identical phenotypic characters in human and chimp in terms of anatomy, physiology, development and other biological features. In fact there is none! A chimp is not even 0.1% human being or a human being 0.1% chimp. A human being differs from chimp in every detail and at every point of the body. The only similarity between chimp and man is in the DNA! The differences in traits, characteristic behaviour, instincts and capabilities between human (Homo sapiens) and chimpanzee (Pan sp.) are far greater than the small degree of sequence divergence (1.3%) could account for.

The chimp-human comparison is a case of similar genomes but dissimilar phenotypes. The reverse case is also known. Caenorhabditis elegans and C. briggsae are physically very similar organisms. It takes an expert to distinguish them. The two have near-identical biology, even down to the minutiae of developmental processes. Surprisingly, however, their genomes are not so similar. C. elegans has more than 700 chemoreceptor genes when C. briggsae gets on by just 430. There are also many genes unique to each of them [10]. Another anomaly is the lack of correspondence in the number of genes (taking for granted the meaninglessness of gene identification) with complexity of the organism. For example, fruit flies have fewer coding genes than roundworms, and rice plants have more than humans [11].

Are these not departures from the expected genome configuration (i.e., genetic information)-phenotype relationship?

g) Many insects exhibit alternative morphologies (polyphenisms) based on differential gene expression rather than genetic polymorphism (differences in genes themselves). One of the best understood insect polyphenisms is the queen-worker dimorphism in honey bees. Both the queens and the workers are females but morphologically distinct forms. Besides, the queen is fertile whereas the worker is sterile. Studies conducted with the bee species Apis mellifera revealed that numerous genes appeared to be differentially expressed between the two castes [12]. The seven differentially expressed loci observed in the study belonged to at least five distinctly different functional groups. The queen and the worker castes in honey bee provide an unfailing proof of natural existence of similar genomes exhibiting dissimilar phenotypes.

How is it possible for similar genes (chemical structures supposed to be encoding similar information) to express differently?

h) “Pseudogenes are similar in sequence to normal genes, but they usually contain obvious disablements such as frameshifts or stop codons in the middle of coding domains. This prevents them from producing a functional product or having a detectable effect on the organism’s phenotype…. The boundary between living and dead genes is often not sharp. A pseudogene in one individual can be functional in a different isolate of the same species… and so technically is a gene only in one strain…. there are other pseudogenes that have entire coding regions without obvious disablements but do not appear to be expressed.” [13].

How can a chemical structure function as gene in one strain and fail to function similarly in another strain?

i) The variation observed in the use of triplet codes among organisms is another issue. Like the pseudogene this aspect is against chemical fundamentals and remains unexplained. The degenerate nature of the biological code implies several triplets coding per amino acid. Further, two amino acids have only one mRNA codon each; AUG for methionine and UGG for tryptophan. Hence 59 degenerate triplets code 18 amino acids; these 18 have two to six synonymous codons each. Choices between synonymous codons are not random; some codons in the set specific to an amino acid are used more than the others [14]. The ‘genome hypothesis’ which tries to explain the variation in codon use states that codon use is species-specific, i.e., each genome or type of genome shows a particular pattern of choices between synonymous codons. Thus overall codon usage differs between taxa; but codon bias is also influenced by other factors like gene length, gene expressivity (the amount of protein made per gene), environment and lifestyle of the organism [15]. The codon bias gives rise to the paradox whether protein evolution determined DNA sequence or DNA commanded protein evolution. Many such dilemmas remain in molecular evolution. The origin of bias in codon and anticodon frequencies continues to elude researchers [14].

How can these be explained?

j) There are many kinds of DNA repairs. Rosenfeld gives a detailed account of the self-healing strategies of the ‘master molecule’. If a base is put in wrong place during replication, there are enzymes to correct the mistake. Purines, without any errors and without any damages drop out by the thousands every day presumably due to wear and tear of existence in the chromosomes only to be promptly replaced by insertases. A base can spontaneously undergo change. A cytosine, for example, will lose an amino group and become uracil. Uracil is perfectly at home in RNA but not in DNA. The enzymes called uracil glycosylases recognize the uracil, remove it and replace it with a new cytosine. Suppose that an error has occurred in one of the DNA strands say, a T has been put across from a G, where a C really belongs. This would give rise to two strands one with a G and the other with a T. The enzymatic apparatus ‘knows’ that cannot be correct, but how does it know whether to replace the C with a T on one strand, or the C with an A on the other? If the replacement takes place not on the right strand, the result would be either death of the cell or a mutation. How does it know which is the authentic original? [16].

How can a chemical structure (DNA) be aware of the change in its elemental composition and arrangement? How can it detect the ‘wrong’ one and ‘correct’ it with the genetic information encoded by it?

Molecular gene remains undefined

a) Although molecular biologists liberally use the term “gene” and claim identification of genes for various characters and diseases, the “gene” remains unknown to them even today. According to geneticist Peter Portin, “The gene is no longer a fixed point on the chromosome, producing a single messenger RNA. Rather, most eukaryotic genes consist of split DNA sequences, often producing more than one mRNA by means of complex promoters and/or alternative splicing. Furthermore, DNA sequences are movable in certain respects, and proteins produced by a single gene are processed into their constituent parts. Moreover, in certain cases the primary transcript is edited before translation, using information from different genetic units and thereby demolishing the one-to-one correspondence between gene and messenger RNA. Finally, the occurrence of nested genes invalidates the simpler and earlier idea of the linear arrangement of genes in the linkage group, and gene assembly similarly confutes the idea of a simple one-to-one correspondence between the gene as the unit of transmission and of genetic function….” [17]. Other leading scientists like Thomas Fogle and Michel Morange also concede that there is no longer a precise definition of what could count as a gene [18, 19]. The objective of genomic research is to ultimately understand the relationships between heritable units and their phenotypes. But it appears that genome concept would not deliver that information. The genome organization is extremely complex. Genes reside within one another, share some of their DNA sequences, are transcribed and spliced in complex patterns, and can overlap in function with other genes of the same sequence families. “Today, in the era of genomic sequencing and intense effort to identify sites of expression, the declared goal is to search for genes, entities assumed to have physical integrity. Ironically, the sharper resolving power of modern investigative tools make less clear what, exactly, is meant by a molecular gene, and therefore, how this goal will be realized and what it will mean”, observes Fogle [18]. These findings clearly expose the meaninglessness of the concept of molecular gene (genome).

When the “gene” remains unknown to biologists, what justification is there in using the molecular gene concept to explain biological attributes and functions?

How can a concept, which scientists cannot define or explain, was accepted in biology in the first place? Is it not strange?

b) Horace Freeland Judson writing in Nature notes: “The phrases current in genetics that most plainly do violence to understanding begin “the gene for”: the gene for breast cancer, the gene for hypercholesterolaemia, the gene for schizophrenia, the gene for homosexuality, and so on. We know of course that there are no single genes for such things.” [20]. Yet we find even now in every biology journal the term “gene” used in the general sense as well as to indicate specific characters.

Although biologists find there is no single gene to characterize an attribute or disease and the journal editors accept it, the same people continue to publish the term “the gene for” even now. If there is no single gene for a character, why papers suggesting “the gene for” continue to be published? Will the use of the term “the gene for” not corrupt science and mislead the public?

Secondly gene counts are also widely published in the journals. If the gene is not definable, how can it be counted? If single genes do not determine the phenotypic characters, what meaning is there in gene counts?

More than six decades have passed since the introduction of the molecular gene concept. Thousands of journals have published several thousands of papers annually in molecular gene-related area literally filling all the physical and virtual spaces in the libraries of the research institutes and universities the world over. Several new fields like bioinformatics, genomics, synthetic biology, etc., have emerged. Thousands of Ph.Ds have been produced. Hundreds of courses are now available in these subjects. Bu to no use! The molecular gene remains even now undefined and unknown! And the phenomenon of life also remains undefined and unexplained. Is it not time to reject the molecular gene concept, which has already proven to be the costliest blunder in science?

Proof of non-molecular existence of biological information

a) In 1970 Miroslav Radman discovered the phenomenon of cell-directed mutagenesis. He found that bacteria harboured a genetic program to make mutations. At that time, no one believed this heretical proposal [21]. In 1988 molecular biologist John Cairns and his colleagues observed induced mutations of various elements of the lac operon changes in Escherichia coli bacteria [22]. Their results were even more shocking than Radman’s. “…depending on their environmental conditions, bacteria might be able to direct mutations to particular genes….Outraged, a number of evolutionary biologists quickly embarked on their own studies to test the notion” [21]. Goodman described the studies conducted by Joshua Lederberg at the University of Wisconsin which showed that mutations for resistance to some antibiotics occurred spontaneously in cells that had never been exposed before to the antibiotics [23]. A recent report of resistance of bacteria to antibiotics also provides evidence of cell-induced mutation [24]. There are several mechanisms such as crossing over (recombination) during meiosis, chromosomal aberrations like deletion, replication, translocation and translocation, non-disjunction, cell divisions (mitosis and meiosis), etc., which are dismissed by biologists as errors or random phenomena. These are not recognized as cell-induced mechanisms to bring about mutations.

These findings are sufficient evidence to establish that mutations are induced from within the cells and that genetic program is not encoded by the DNA. The genetic program exists independently of DNA structure.

Why these findings are not accepted by the scientific community with due importance but are sidelined to uphold the concept that biological information exists as molecules?

b) A fundamental feature of chemical molecule is that it cannot lose its properties. The genome appears to be an exception to this rule also. Going by the present concept of particulate genetic program, a cell carrying the genome should invariably show the life properties. However a dead cell with its genome remaining intact fails to exhibit “life” clearly indicating the genome does not encode the biological program.

When I put this question to Nature (Scitable), I received the least expected silly answer from its expert, which is no answer to my question at all. The Scitable answer [25] is reproduced below:

“Questions like yours about life and death spurred the earliest scientific inquiry and keep the field moving forward. It is possible for the genome to be intact in dead cells. For example, think about your local library: at night, nothing is going on and none of the books can be checked out, but all the books would still be there. Similarly, the genetic code is still present in dead cells; however, the absence of certain key biochemical processes, such as transcription and translation, makes reading the code (like checking books out from a library) impossible. Death can be understood at two levels: at the level of the organism and at the level of the cell. In the first case, death arrests all key biochemical processes. No key enzymes are available to translate mRNA and no amino acids are linked to create polypeptide chains. But in the second case death can also help other cells in the same body. This process is called programmed cell death (or apoptosis) and involves a series of biochemical events leading to changes in cell shape followed by cell death. These changes in cell shape include blebbing, which occurs when a portion of the cytoskeleton separates from the plasma membrane and creates an irregular bulge called a bleb. This is like the locking of a door — a change in cell structure arresting cell activity. The cell membrane also loses symmetry and detaches from the cytoskeleton, which leads to cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and the eventual damaging of the cell’s genome. All these processes make it harder for the cell’s transcription machinery to read the genetic code, just as locked doors make it difficult for us to check out books from the library at night. A second type of cell death can actually damage neighboring cells, like a fire in the library that spreads to the bookstore across the street. This type of cell death is called necrosis and results from acute cellular injury or infection. Cells undergoing necrosis eventually burst and release their cellular contents, which can damage neighboring cells and induce inflammation. You’re right: the genetic code is essential for all life. But key proteins required to read the genetic code stop working in dead cells. Despite the great wealth of information contained within the genetic code, a genome alone doesn’t lead to the creation of proteins that serve as the basis of life.”

Clearly there is no answer to the natural irreversible cessation of all biological activities at some point of time during the life of an organism with all its material contents including genome intact. It is impossible to explain the cessation of biological activity of the organism (i.e., death) based on molecular gene concept when the genome is intact. In case it has undergone alteration at death, its repair should restore the life of the organism. Further the body starts decaying immediately after death. What makes the body resistant to microbial decomposition and susceptible to decay when the material body is identical prior to and after death is also unexplainable. Clearly the genetic program exists independently of any chemical structure. The phenomenon of life and death cannot be defined or explained based on material gene and will ever remain unexplained in biology!

Is it possible for biologists to refute these conclusions?

For a discussion of nonmaterial basis of life please see my post ‘Life is nonmaterial phenomenon’ in this forum in the same section ‘Molecular biology’. The subject is covered in detail elsewhere [26, 27, 28].

References

1. Johannsen, W. 1911. The genotype conception of heredity. The American Naturalist 45, 129-159.

2. Morgan, T. H. 1935. The relation of genetics to physiology and medicine. Les prix Nobel en 1933. Imprimerie Royale, Stockholm, 1-16.

3. Muller, H. J. 1951. The development of the gene theory. In Leslie C. Dunn (ed.), Genetics in the 20th Century. Essays on the Progress of Genetics During its First 50 Years. MacMillan, New York 1951, 77-99.

4. Rheinberger, Hans-Jörg, Müller-Wille, Staffan, “Gene”, The Stanford Encyclopedia of Philosophy (Winter 2004 Edition), Edward N. Zalta (ed.), URL = http://plato.stanford.edu/archives/win2 … ries/gene/ Accessed on 11 December 2005.

5. Watson, J. 1973. The Molecular Biology of the Gene, third edition. Menlo Park, California: The Benjamin/Cummings Publ. Co.

6. Pearson, H. 2003. DNA: Beyond the double helix. Nature 421: 310-312.

7. Gottlieb et al., “BAK1 gene variation and abdominal aortic aneurysms”, Human Mutation Vol. 30, 2009, pp. 1043. DOI: 10.1002/humu.21046.

8. DNA not the same in every cell of body: Major genetic differences between blood and tissue cells revealed,” ScienceDaily (July 16, 2009).

9. Wells, J. Homology in Biology: A Problem for Naturalistic Science. By Jonathan http://www.trueorigin.org/homology.asp Retrieved 24 November 2001.

10. M. Blaxter, M. 2003. Two worms are better than one. Nature 426:395-396.

11. W.W. Gibbs, W.W. 2003. The unseen genome: Gems among the junk. Scientific American 289, November 2003, pp. 46-53.

12. Evans, J.D. and Wheeler, D.E. 1999. Differential gene expression between developing queens and workers in the honeybee, Apis mellifera. Proc. Natl. Acad. Sci. USA. 96:5575-5580.

13. Snyder, M. and Gerstein, M. 2003. Genomics: Defining genes in the genomics era. Science 300:258- 260.

14. Grantham, R.L. Codon usage in molecular evolution. doi: 10.1038/npg.els.0001806.

15. Grantham, R. et al., 1981. Codon catalog usage is a genome strategy modulated for gene expressivity. Nucleic Acids Res. 9:43-47.

16. Rosenfeld, A. 1981. Master molecule heal thyself. Mosaic 12(1).

17. Portin, P. 1993. The concept of the gene: Short history and present status. The Quarterly Review of Biology 68:173-223.

18. Fogle, T. 2000. The dissolution of protein coding genes in molecular biology. In Peter Beurton, Raphael Falk, and Hans-Jörg Rheinberger, The Concept of the Gene in Development and Evolution. Historical and Epistemological Perspectives, Cambridge University Press, Cambridge, pp. 3-25.

19. Morange, M. 2000. The developmental gene concept: History and limits. In Peter Beurton, Raphael Falk, and Hans-Jörg Rheinberger (eds.), The Concept of the Gene in Development and Evolution. Historical and Epistemological Perspectives, Cambridge University Press, Cambridge, pp.193-215.

20. H. F. Judson, H.F. 2001. Talking about the genome. Nature 409:769.

21. Chicurel, M. 2001. Can organisms speed their own evolution? Science 292(5523):1824-1827.

22. Cairns, J., Overbaugh, J. and Miller, S. 1988. The origin of the mutants. Nature 335:142-145.

23. Goodman, B. 1992. Directed mutations: Heredity made to order. Mosaic 23(1):24-33.

24. Kohanski, M.A., DePristo, M.A. and J. J. Collins. 2010. Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Molecular Cell 37(3):311-320.

25. http://www.nature.com/scitable/my-discussion/474.

26. Wahid, P.A. 2007. The Great Gene Fiasco: The Quran Defines Life. Adam Publishers and Distributors, New Delhi.

27. Wahid, P.A. 2006. The Computer Universe: A Scientific Rendering of the Holy Quran (2006), Adam Publishers and Distributors, New Delhi.

28. Wahid, P.A. 2010. Memetics of the computer universe based on the Quran. J. Software Engineering & Applications 3:728-735.

[JackBean]

You’re lucky, that we were part of the Habsburgmonarchy, so I won’t take it as insult claiming Mendel being Austrian :devil:

Although you seem to be a scientist (at least you obviously publish "something"), you’re apparently missing several important points and "new" discoveries.
I didn’t read it all (who would? :roll:), but few points:
the information coded by DNA is changing in time due to mutations with several mechanisms. But that’s not provably what you asked for. You probably meant changes in development during organism ontogenesis. These are caused by changes in gene expression, not in DNA.
It’s clear nowadays, that protein-coding sequences play only minor role in DNA (BTW there are genes, which do not code for proteins). Actually, whole genome is widely transcribed. The other parts result in all kinds of RNAi.
I don’t see any problem in gene definition, just because it’s alternatively spliced. It’s still just one gene on DNA producing several different RNAs (and proteins).
It may be true, there is nothing like gene for cancer, but that doesn’t mean there are not several genes involved in cancer occurence. And more importantly, we do have gene for glukose kinase, for pyruvate dehydrogenase etc.

[DougB]

I think there is some history to development of genetics as a study in your post. Perhaps one thing we can take from this is that genetics as a field is constantly evolving. One new area that seeks to explain gene expression is epigenetics, how something external influences gene expression. One example is cancer. Let’s say we have two individuals both carrying a set of genes coding for cancer. Yet one person develops cancer and the other does not. Why? It could be the afflicted person also smokes. So, how does smoking cause cancer?

Gene expression could be influenced by many things other than proteins called cofactors. Perhaps tobacco contains a chemical that acts as a cofactor for cancerous genes. Therefore, we conclude that smoking causes cancer.

The question of why cells with identical genomes develop into different tissue is still difficult to answer. Forensics benefits from this fact. Blood cells acquired from a crime scene can be genetically compared to cheek cells from a suspect. However, blood cells and cheek cells are clearly different. The process of cell differentiation is not fully understood. Proximity is somehow involved. During early development, cells in contact with each other generally develop into similar tissue. While other cells also in contact develop into different tissue. Perhaps it is the presence of cofactors that lead to cell differentiation. Perhaps diffusion rates depletes the concentration of certain cofactors so only cells in one area develop into a specific tissue. Of course this bring question as to where the cofactors come from.

One process we do have a better understanding is why progeny different from parents. Mutation only explains one reason. Children acquire two sets of genes, one maternal and one paternal. Therefore children have mixed qualities from both parents. The process of meiosis and crossover explain more differences. One parent could have genes for blue eyes, blond hair and type A blood on one chromosome. The sister chromosome has genes for brown eyes, red hair and type B blood. Crossing over repositions the genes so one is blue eyes, red hair and type B blood versus brown eyes, blond hair and type A blood.

Two hundred years ago, we did not know about bacteria. Now we have sequenced the genomes from many bacteria. One hundred years ago, we did not know what DNA was. Now we can sequence whole genomes in a week. Imagine what we will know fifty years from now.

[AstraSequi]

A lot of your writing seems to resemble a persuasive essay rather than scientific criticism. For example, your introductory section (up until your first heading) seems to be unnecessary to any argument you might be making.

(And increasing your concision would also make people much more willing to engage with you. Tell me, what is the core of your argument in a single paragraph of 200 words or less?)

There are also some clear inaccuracies. For example:

quote :

there is only one molecule (DNA) in the whole universe that can encode genetic information

quote :

If the genomes of the cells in a body are identical, all the cells should carry identical information.

quote :

A fundamental feature of chemical molecule is that it cannot lose its properties.

And many others both explicit and implicit. I think you need to do more research on the topics you’re trying to discuss – and even if you think a point supports your position, you need to first spend some time to make sure that the point is accurate, even if you feel like continuing wouldn’t be worth your time (http://lesswrong.com/lw/km/motivated_st … tinuation/).

More generally, I think one problem is that you think that genes are supposed to be deterministic. Of course, there are other inputs as well, namely environmental ones. The genome specifies a range of possible responses to the environment.

[Wallyanna]

Interesting paper. Well referenced, many quotes from well qualified scientists. The author did do a very good job of gathering information and some of the questions are certainly good questions. They are just the sort of questions that will inspire geneticists to continue to find more and more answers, perhaps in time developing brand new fields of study.
But I agree with astrasequi here that your article is written as a persuasive argument rather than as a scientific paper.
If others here will read a bit further, the signature of the writer and the last three references will show where the writer is "coming from"
with his efforts to persuade.
Are you a scientist, or an Imam? Either way you are very intelligent to be able to put together this article, and especially so if you are not a scientist as well as a Muslim, because you had to have understood much of what you quoted in order to try to use it to persuade. Like astrasequi said, though, you made a few errors that she caught right away.
Nevertheless, your comprehension is admirable for a non scientist if you are not one.
However the gaps in the knowledge that seem to be expressed by the scientists you quote,(I would
have to read the articles to see if you cherry picked and quoted out of context) and your evidence that some scientists may not be using clear and concise wording for articles regarding genetic links
to diseases, all in all your scientific quotes and questions do not prove the Quran.

Science doesn’t prove spiritual things. Sometimes it SEEMS to seek to disprove spiritual things but it really doesn’t do that either. Although it might occasionally accidentally seem to disprove religious dogmas the dogmatic won’t pay attention to it anyhow, so that sort of thing changes nothing in the minds of the dogmatic, and becomes a waste of effort in the long run.

Spiritual matters aren’t the bailiwick of science.

Meanwhile we all can hope that new knowledge found in science will be used for the benefit of us
all, and that good intentions don’t pave the way to disasters as new scientific knowledge is utilized in future endeavors.

[AstraSequi]

quote :

… you had to have understood much of what you quoted in order to try to use it to persuade. Like astrasequi said, though, you made a few errors that she caught right away.

I will just point that some people most certainly do quote scientists in great detail without understanding; and also that there are far more than "a few" errors. I only mentioned several of the most egregious.

[PAWahid]

There are a few points raised by AstraSequi and Wallyanna that need clarification from my side.

AstraSequi says: “A lot of your writing seems to resemble a persuasive essay rather than scientific criticism.”

I beg to differ with you. It is both persuasive and scientific criticism. What I believe based on the available literature on molecular gene is that it is chemically and hence scientifically wrong. I have presented enough scientific reasons for that. Therefore it is indeed scientific criticism. Can you please explain why you do not consider my criticism as scientific? Regarding the introductory part, for a geneticist the introduction I have given may appear redundant, but certainly others will find it quite useful.

AstraSequi says: “Tell me, what is the core of your argument in a single paragraph of 200 words or less?”

I argue that the molecular gene concept is wrong. Biological information is not encoded by any chemical structure. Chemical structure encodes only chemical information. The DNA structure encodes chemical information relating to its physical and chemical properties and behaviour like any other structure. Biological information is nonphysical or nonparticulate as originally proposed by Wilhelm Johannsen in 1909. Today in the era of computer technology the nonphysical or nonmaterial phenomenon can be explained. It is no longer weird. The nonphysical existence of biological information can be explained by the computer model of organism. That is, biological program exists as stored information on chromosome structure like software exists on a computer hard disk. The software of a computer is not encoded by the chemical structure of the hard disk; it only serves as medium for storage. Likewise, some or all of chromosome structure (DNA included) may be serving as the storage medium. Johannsen’s nonphysical gene agrees well with the Quranic revelation of soul as the cause of life. The invisible software that drives a computer is akin to the invisible soul (biological program) that drives an organism (biocomputer or biorobot system) as given in the Scripture. This would imply that the entire literature pertaining to molecular gene as the biological information is wrong.

AstraSequi says: “There are also some clear inaccuracies. For example: there is only one molecule (DNA) in the whole universe that can encode genetic information”

What is wrong with this statement? Perhaps you may add RNA and protein also. What I refute is that none of the chemical structures encodes biological information. The clear evidence is that a dead cell has all its genome intact. If it encodes biological information, the dead cell should show life. In other words, so long as genome is present in a cell it cannot die. Even if it is damaged, repair of the genome should bring it back to life.

Another inaccuracy indicated is: “If the genomes of the cells in a body are identical, all the cells should carry identical information.”

Identical structures should have identical information. How can it be different? My statement is not at all incorrect. Please tell me why you consider it as inaccurate?

A third inaccuracy mentioned is: “A fundamental feature of chemical molecule is that it cannot lose its properties.”

This statement is also one hundred per cent correct. Can you please cite just one example of a chemical structure losing its properties when the structure is intact? When you have doubts about my concept of nonphysical biological information although it is supported by scientific facts, why do you consider molecular gene with no scientific proof to support it as correct? Can you please explain?

Apart from these, there is some query from Wallyanna.

“Are you a scientist, or an Imam?”

I am basically a scientist (chemist). I am a Muslim. I use my true name in my posts unless the blogger asks to give a different name. I do not fix boundaries in knowledge as religion (spiritual), science, etc. I believe in things that my mind can scientifically explain to me. It is my conviction to be a truth seeker. However the current trend is we blindly believe in everything that is published in science journals, and we blindly disbelieve in everything that is in the Scripture. This trend should go and we should be prepared to call a spade spade. Now in the case of gene, the Scripture is true. But just because the current trend is to question the Scripture, people do that. They do not question the molecular gene despite the fact that even biologists who proposed that concept do not know what it is! I wonder how could they propose even without knowing what it is! More than that how the scientific community accepted it as scientific truth!

[JackBean]

quote PAWahid:

AstraSequi says: “Tell me, what is the core of your argument in a single paragraph of 200 words or less?”

I argue that the molecular gene concept is wrong. Biological information is not encoded by any chemical structure. Chemical structure encodes only chemical information. The DNA structure encodes chemical information relating to its physical and chemical properties and behaviour like any other structure. Biological information is nonphysical or nonparticulate as originally proposed by Wilhelm Johannsen in 1909. Today in the era of computer technology the nonphysical or nonmaterial phenomenon can be explained. It is no longer weird. The nonphysical existence of biological information can be explained by the computer model of organism. That is, biological program exists as stored information on chromosome structure like software exists on a computer hard disk. The software of a computer is not encoded by the chemical structure of the hard disk; it only serves as medium for storage. Likewise, some or all of chromosome structure (DNA included) may be serving as the storage medium. Johannsen’s nonphysical gene agrees well with the Quranic revelation of soul as the cause of life. The invisible software that drives a computer is akin to the invisible soul (biological program) that drives an organism (biocomputer or biorobot system) as given in the Scripture. This would imply that the entire literature pertaining to molecular gene as the biological information is wrong.

To my knowledge, even the computers need to store the information somehow and it is in the form of bits, i.e. either 0 or 1. Similarly, in the DNA, the A,C,T and G codes for the information.
I think it was Pasteur who proved, that life cannot originate from non-living.

quote PAWahid:

AstraSequi says: “There are also some clear inaccuracies. For example: there is only one molecule (DNA) in the whole universe that can encode genetic information”

What is wrong with this statement? Perhaps you may add RNA and protein also. What I refute is that none of the chemical structures encodes biological information. The clear evidence is that a dead cell has all its genome intact. If it encodes biological information, the dead cell should show life. In other words, so long as genome is present in a cell it cannot die. Even if it is damaged, repair of the genome should bring it back to life.

That’s not true. You can take artificial genome or even the genome from dead cell (if it’s still intact, but it gets usually quickly degraded), insert it into cell and you will get viable cell. And it’s not true that cell cannot die as long as genome is present. The genome is hardly first to be affected by cell death.

quote PAWahid:

Another inaccuracy indicated is: “If the genomes of the cells in a body are identical, all the cells should carry identical information.”

Identical structures should have identical information. How can it be different? My statement is not at all incorrect. Please tell me why you consider it as inaccurate?

You have obviously skipped not only RNAi lecture, but also my post where I refer to it.
It is true that all the cells carry identical information, but not all information is used in all cells. Imagine skyscaper being built. People at all levels have blueprints for the whole skyscaper, but they will use only the relevant part which shows their level.

[AstraSequi]

I really don’t have much time to discuss, so I’ll make this my last post.

With regards to the reply that Jack did not address:

quote :

Can you please cite just one example of a chemical structure losing its properties when the structure is intact?

Since you’re a chemist, you surely know about the kinetic isotope effect. Nuclear decay will change the properties of a molecule, without changing chemical structure.

But regardless, that is not what you said the first time. You did not say “a chemical structure cannot lose its properties when the structure is intact.” (Of course, every single chemical reaction involves a change in properties, and these occur in all cells at an incredibly fast rate.)

The sentence you wrote on its own could potentially be interpreted either way. However, the argument that followed the claim assumed that such changes cannot occur – you said that if DNA has the property of “life,” then a dead cell with an intact genome could not exist. Of course, “life” is not a property of DNA but the entire system, which is another of the misconceptions that I referred to above.

quote :

It is both persuasive and scientific criticism.

This is possible, but it is generally bad form in science. I assumed that if you were posting here, you were intending to present your ideas to scientists. I apologize if that is not the case.

quote :

Can you please explain why you do not consider my criticism as scientific?

I have not made this claim, as I did not evaluate it in detail. However, given the misconceptions you have incorporated into the discussion, my impression is that it is unlikely.

quote :

…why do you consider molecular gene with no scientific proof to support it as correct?

The scientific proof actually exists. There is lots of it, so I suggest that you look it up yourself. 🙂

One good way approach this would be to ask yourself what specific experiment (as simple as possible) would prove it correct, and then afterwards look (or ask here) to see whether it has been done. (In fact, this is a general strategy – it is applicable to almost any proposition you can think of.)

quote :

I argue that the molecular gene concept is wrong…This would imply that the entire literature pertaining to molecular gene as the biological information is wrong.

Sorry, I wasn’t specific enough. This still contains many unsupported statements, for which evidence must still be provided. The explanation should refer back to the results of the actual experiments and why they are in support of your position.

However, I still think that you made the argument much clearer, so well done. 🙂

[PAWahid]

AstraSequi wrote: “With regards to the reply that Jack did not address:
“Can you please cite just one example of a chemical structure losing its properties when the structure is intact?”

Since you’re a chemist, you surely know about the kinetic isotope effect. Nuclear decay will change the properties of a molecule, without changing chemical structure.”

Dear AstraSequi, you are misleading people by your comments of this kind; that too to support the erroneous molecular gene theory. Nuclear decay changes the nuclide. There are atomic species for an element; these species we distinguish as “nuclides”. For example P-31 with 15 protons and 16 neutrons is the stable phosphorus nuclide, which is not radioactive. When the neutron number increases to 17 it becomes P-32 and its property changes. It becomes radioactive. This nuclide is still called phosphorus because the criterion we adopt to distinguish between elements is the proton number. Both P-31 and P-32 have the same proton number, i.e., 15. When a radionuclide decays by emitting radiation, there again it changes. That is why its property changes. What you said is wrong. For example P-32 on emission of a beta particle becomes sulphur.

My response: “It is both persuasive and scientific criticism.”

AstraSequi wrote: “This is possible, but it is generally bad form in science. I assumed that if you were posting here, you were intending to present your ideas to scientists. I apologize if that is not the case.”

A scientific criticism is also persuasive because the scientific evidences presented to support the criticism direct you to the truth. It is what science is. What do you mean by “it is generally bad form in science”?

I think all my arguments against the molecular gene are adequately substantiated by scientific reports cited by me. The reader can very well verify the papers I cited and confirm their relevance. If AstraSequi is still not convinced, I have this last question. Biologists believe that a living organism is nothing but material like any substance. It does not contain anything nonmaterial (or nonmolecular). What I argue is that it contains nonmolecular biological program that is stored on the chromosomes. It is not encoded by any chemical structure including DNA. It is like the storage of computer software on hard disk. The chemical structure of the hard disk does not encode the information stored on it. The chemical structure only encodes chemical information responsible for its properties and behaviour and not the information we store.

If a living organism is merely chemical molecules and does not have any nonmolecular component, what is the difference between the living and dead counterpart? At the time of death, the material is intact. Even if there is any change in any molecule, as I mentioned earlier, its repair should restore its life. Molecular gene concept does not and cannot differentiate between the living and dead states of a body. Can you please explain this scientifically? If you cannot, how can you still argue that molecular gene encodes biological program and that the concept is correct?

[JackBean]

Why do you hesitate to respond to counterarguments in our previous posts?

How is it that we are able to run reactions in vitro? Are we able to get the ghost into our eppies?

What’s the difference between government and chaos? All the parts are present in both cases, the only difference is organisation.

[PAWahid]

Dear Jackbean: My arguments against molecular biological program have been posted here. I have also summarized my arguments in the last two paragraphs of my previous reply to AstraSequi. My argument is very clear. Also I have posted my concept of non-molecular biological program entitled “Life is nonmaterial phenomenon” in the same section (Molecular Biology) in the light of a computer model of organism. Unless I get a scientific response that can challenge either of these, there is no need of further response from me.

[JackBean]

If this is how you think scientific dialogue should look like than there is no reason to keep this topic opened.

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