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Richard v. Sternberg

The Immaterial Gene How DNA sequencing projects have revealed the gene to be a multilevel mediator of information that lacks a physical description. Richard v. Sternberg. We are undoubtedly familiar with the atomistic or “beads on a string” view of the gene . Developmental “Black Box”. ….

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Richard v. Sternberg

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  1. The Immaterial GeneHow DNA sequencing projects have revealed the gene to be a multilevel mediator of information that lacks a physical description Richard v. Sternberg

  2. We are undoubtedly familiar with the atomistic or “beads on a string” view of the gene Developmental “Black Box” … Protein 3 Protein 1 Protein 2 … Gene 3 Gene 2 Gene 1

  3. This classical model of a gene was developed to support the Darwinian “New Synthesis” and was based on these assumptions: • Genes are discrete physical units • Only the collection of genes (genotype) is real; organismal development and traits (the phenotype) are epiphenomenal • The structure of the genotype can be explained solely in terms of population genetics (mutation and selection/genetic drift)

  4. This picture of genes as independent and mutable particles was the basis of the neo-Darwinian model of macroevolutionary transitions. Mutations Genotype ‘Z’ Genotype ‘W’

  5. How so? Consider the presuppositions of the model… 1) Genes are the only carriers of phenotypic determinants; no “laws of form” exist phenotypes mirror genotypes. 2) Genotypes are aggregates of simple entities that are constantly changing phenotypes are always transforming. 3) Loci can be combined and mutated in an unlimited way morphological evolution is “open-ended.” 4) Any two sets of genes are connected by a finite number of mutations morphological gaps are illusory.

  6. Then the molecular organization of DNA was discovered. This enabled a radically materialist picture of the gene to be proposed…The “Central Dogma.”   RNA Protein DNA Or  DNA

  7. The Central Dogma conflates a polymer (DNA) with information; the latter is nothing but the former. So by definition, mutations in DNA  changes in information.The process is simple: …ACCGTTAACGCGCTACGT… …ACCGTTAACTCGCTACGT…

  8. In theory, then, any two species can be interconverted by changing their DNA scripts. This is called the “Jurassic Park” or “genetic program” model. = DNA Mutations = DNA*

  9. Mutations also generate a lot of “junk” or DNA gibberish according to the model, with selection keeping the useful genetic codes intact.Genes are thus seen as isolated “beads” that are interrupted by junk, and separated by long strings of such “non-coding” DNA.

  10. Consider this line from Dante’s Paradiso as being akin to a gene: Although the veil, that from her head descended,  Encircled with the foliage of Minerva,  Did not permit her to appear distinctly, In attitude still royally majestic  Continued she, like unto one who speaks,  And keeps his warmest utterance in reserve: "Look at me well; in sooth I'm Beatrice!” From the standpoint of the atomistic, Darwinian model of the “gene” we have something like this: …SKJDJgsdgfqipowNcnehfhwefnWEAFE,CNwehfodfjojn,cNRONV,NV/N/VKNDSKVNz,zn,nkln,XNCNsoefweiw,vzewfscmXCsAlthoughnxscCQIWETtheveil,thatfromherasdbABSCBJbwp’/;MLCheaddescended,j.JAIOEROHSCnscbBSKJ.DmcXM.nsNDJCsdjk.KSHEFEFODFEncxxxxxxircledwiththeA8Y42WHDklasd283y8yr230refAASKLD2HR;akwdnEWIUGRUIGJDBfoliageofaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaMinera,99#Didnotpermitherweiorwfsdcjdsfu3grnwftoappearreDdistinctly,bInattitttttttttttttttttttude%^ds@stillroyallywejbbsasdhiaskcn%^%$hhbffmajesticContinuedshe,””’likeuntoone……..whospeaks,__iwefnSWFsmkkjdfvairghqndfvAndkeepshis))warmestutterance<<<>>>inreserve:AAAAAAAAAAAAAA"Lookatme~well;inyyysoothI'mBeatrice!”SHR3RMSPOCJ09UR 9RHW%&&d$w$trscvy*njbhj bfvdt…

  11. Hence, mutations are like monkeys at a typewriter generating line after line of mostly gibberish. Natural selection on the other hand is the force that keeps only the meaningful words and therefore “writes” sentences. This is the crux of the Darwinian gene concept—more or less randomly arranged messages that have been retained by evolution.

  12. The influence of this idea of the genetic locus is profound… It serves as the framework for the arguments of Richard Dawkins (The Selfish Gene, The Blind Watchmaker, Climbing Mount Improbable, etc.) and many other “scientific atheists.” It is used as an argument to justify animal-human hybrids/chimeras and the granting of human rights to great apes (Spain). After all, what supposedly separates us from chimps (and any other species) is a series of mutations—mostly junk. It is the centerpiece of the case for “theistic” Darwinian evolution in Francis Collins’s The Language of God and Ken Miller’s works.

  13. The question is: What evidence do we have that this model is correct?

  14. The First Clue

  15. During the 1990s it became apparent that every locus is a non-randomly arranged set of coding modules Tissue-specific enhancers SINE Mini-satellite Imprinting element Nuclear matrix attachment site snoRNA gene Promoters Exon A-2 Exon A-1 microRNA genes Exon B-1 Exon B-2 Exon A-3 Virus-like element Silencer Terminator Exon A-4 Nuclear matrix attachment site

  16. Data also emerged post-2001 revealing that protein-coding genes are mainly clustered, overlapping, and interleaved along chromosomes—yet they comprise but a few percent of the total DNA. Gene cluster control switches “Gene” 4 “Gene” 2 “Gene” 3 “Gene” 5 “Gene” 1

  17. Even more startling was discovery in 2004-2007 that making RNA copies often begins in one “gene” and ends in another, and occurs on both DNA strands and in “non-gene” regions transcripts “Gene” 4 “Gene” 2 “Gene” 3 “Gene” 5 “Gene” 1

  18. As a consequence of these results, a physical description of the “gene” is currently lacking. What we do know is that each locus:- Is hierarchically ordered - Has “multilevel optimization” of many different types of information- Is connected by “coding chains” with adjacent loci, and genes on other chromosomes.

  19. The existence alone of overlapping protein-coding frames is “virtually impossible by chance.”* *Chung, W.-Y et al., 2007. A first look at the ARFome: Dual-coding genes in mammalian genomes. PLoS Computational Biology 3(5): e91.

  20. The Second Clue

  21. Other key pieces of evidence also began to accumulate. For example, it was found that most “genes” encode many different transcripts (over 38,000 in some cases!) / / Gene transcription / / AAUAAAA… Primary transcripts / / AAUAAAA…

  22. And the splicing of RNAs generates yet more gene products / / AAUAAAA… / / AAUAAAA… RNA splicing AAUAAAA… AAUAAAA… AAUAAAA… AAUAAAA… AAUAAAA…

  23. In addition, it was soon realized that the “junk” sections of RNAs are processed into a host of functional sequences AAUAAAA… AAUAAAA… AAUAAAA… AAUAAAA… AAUAAAA… Processing of exons and introns snoRNAs (RNA editing) ncRNAs (various roles) microRNAs (regulatory)

  24. And now it is known that cellular pathways literally rewrite genetic scripts to make new transcripts and proteins, a widespread phenomenon called “RNA editing” Fig. 1, Lev-Maor, G. et al., 2007. RNA-editing-mediated exon evolution. Genome Biology 8(2): R29.

  25. Clearly, the “gene” provides the substrate for many types of information that are layered on by the cell. In fact…- Many RNAs, because of being rearranged and edited, do not mirror any DNA sequence - The RNA-level codes that are formed are often topological in nature - Many RNA-level codes are sequence- independent Thus the phenotype even at the most basic level cannot be reduced to the genotype.

  26. The Third Clue

  27. So-called junk DNA elements are replete with experimentally demonstrated functions:

  28. Although less than 2% of genomic DNA in many vertebrates (e.g., mammals) can be placed in the traditional “gene” category, nearly all sequences are transcribed in a cell- and tissue-specific manner.

  29. The Fourth Clue

  30. Co-expressed loci are clustered together along in the nucleus, sometimes to “create” genes Nuclear compartment with concentrated transcription factors Chromosome 5 loop Chromosome 21 loop Chromosome 2 loop

  31. Beyond Genes: DNA Sequences as Context-Dependent, Data-Storage Regions Given all the evidence we now have available,a new model of the genome is now emerging.

  32. Emerging View of “Genes”

  33. But What Does This Entail for Intelligent Design?

  34. Gen(om)e organization is patterned to be maximally informative. The overlapping codes observed are known to be evolutionarily “costly,” because random mutations will likely have a deteriorating effect, not an enstructuring role (Chung, W.-Y et al., 2007). So the complex specified information entailed by any genomic region is orders of magnitude higher than previously suspected by, say, Dembski—and far, far beyond the reach of chance.

  35. Any seemingly random aspect of chromosome sequence arrangement is not. A case in point involves endogenous retroviruses (ERVs): A. Human ERVs contribute 51,197 promoter elements that initiate transcription at various stages (Conley et al., Bioinformatics 24: 1563-1567, 2008). B. Mouse ERVs are highly expressed at the 2-cell embryo stage (and are the earliest to be transcribed in the zygote) and are essential for ontogenesis (Kigami et al., Biology of Reproduction 68: 651-654, 2003).

  36. This implies that the taxonomically-specific formatting, indexing, punctuation, etc., of genomes was precisely “written.”

  37. Morphogenetic information is not reducible to the genotype—though it is strongly dependent upon it. Therefore, changes in DNA do not equal changes in the information that enstructures the bodyplan.

  38. Fig. 4. A self-sustained posttranslational oscillator (PTO) embedded within a transcription and translation feedback loop (TTFL) C. H. Johnson et al., Science 322, 697 -701 (2008) Published by AAAS

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