The Immaterial Gene How DNA sequencing projects have revealed the gene to be a multilevel mediator o

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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

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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
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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)

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• 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
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• 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.

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Then the molecular organization of DNA was
discovered. This enabled a radically materialist
picture of the gene to be proposedThe Central
Dogma.
?
?
RNA
Protein
DNA
Or
?
DNA
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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
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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
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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.
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Consider this line from Dantes 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,cNR
ONV,NV/N/VKNDSKVNz,zn,nkln,XNCNsoefweiw,vzewfscmXC
sAlthoughnxscCQIWETtheveil,thatfromherasdbABSCBJbw
p/MLCheaddescended,j.JAIOEROHSCnscbBSKJ.DmcXM.ns
NDJCsdjk.KSHEFEFODFEncxxxxxxircledwiththeA8Y42WHDk
lasd283y8yr230refAASKLD2HRakwdnEWIUGRUIGJDBfoliag
eofaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaMinera,99Didnotp
ermitherweiorwfsdcjdsfu3grnwftoappearreDdistinctly
,bInattitttttttttttttttttttudeds_at_stillroyallywej
bbsasdhiaskcnhhbffmajesticContinuedshe,like
untoone..whospeaks,__iwefnSWFsmkkjdfvairghqndfvA
ndkeepshis))warmestutteranceltltltgtgtgtinreserveAAAAAA
AAAAAAAA"LookatmewellinyyysoothI'mBeatrice!SHR3
RMSPOCJ09UR 9RHWdwtrscvynjbhj bfvdt
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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 conceptmore or less randomly
arranged messages that have been retained by
evolution.
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• 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 mutationsmostly junk.
• It is the centerpiece of the case for theistic
  Darwinian evolution in Francis Collinss The
  Language of God and Ken Millers works.

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• The question is What evidence do we have that
  this model is correct?

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The First Clue
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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-1
Exon A-2
microRNA genes
Exon B-1
Exon B-2
Exon A-3
Virus-like element
Silencer
Terminator
Exon A-4
Nuclear matrix attachment site
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Data also emerged post-2001 revealing that
protein-coding genes are mainly clustered,
overlapping, and interleaved along
chromosomesyet they comprise but a few percent
of the total DNA.
Gene cluster control switches
Gene 4
Gene 2
Gene 3
Gene 5
Gene 1
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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
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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.
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• 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.
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The Second Clue
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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
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And the splicing of RNAs generates yet more gene
products
/
/
AAUAAAA
/
/
AAUAAAA
RNA splicing
AAUAAAA
AAUAAAA
AAUAAAA
AAUAAAA
AAUAAAA
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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)
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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.
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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.
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The Third Clue
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So-called junk DNA elements are replete with
experimentally demonstrated functions
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• 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.

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The Fourth Clue
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Co-expressed loci are clustered together along in
the nucleus, sometimes to create genes
Nuclear compartment with concentrated transcriptio
n factors
Chromosome 5 loop
Chromosome 21 loop
Chromosome 2 loop
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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.

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Emerging View of Genes
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But What Does This Entail for Intelligent Design?
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• 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, Dembskiand
  far, far beyond the reach of chance.

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• 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).

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

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• Morphogenetic
• information is not
• reducible to the
• genotypethough it is
• strongly dependent upon
• it. Therefore, changes in
• DNA do not equal
• changes in the information
• that enstructures
• the bodyplan.

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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