Reorganizing the Genome Information Generating or Information Shuffling Richard v' Sternberg

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Reorganizing the Genome Information Generating
or Information Shuffling?Richard v. Sternberg
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Genome Reorganization and Information

• A thought experiment
• Office workspaces can be rearranged with ease.

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Genome Reorganization and Information

• Question does this shuffling of components
  generate anything really new? configurations not
  already there to begin with?

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Genome Reorganization and Information

• If not, why not?

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Genome Reorganization and Information

• Yet genomes are rearranged in similar ways all
  the time
• Genome plasticity sites in bacterial genomes
  (e.g., phase variation genes)
• Repetitive DNA variation in prokaryotes and
  eukaryotes such as movements of transposable
  elements
• The construction of macronuclear genomes in
  ciliate protozoa
• Generation of immunoglobulin and T-cell receptor
  gene variability in vertebrates
• Mating-type switching in yeast

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Ciliate Genome Reorganization
MIC
MAC
Meiosis/ Nuclear Exchange
Pairing of Cells
Nuclear Fusion/ Duplication of Zygotic Nucleus
Development of Macronucleus/ Nuclear Degeneration
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Genome Reorganization and Information

• Ciliate protozoa literally construct their genes
  de novo during macronuclear development by
  unscrambling micronuclear sequences.

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Unscrambling the a-subunit gene of the
telomere-binding protein in Oxytricha nova
IESs
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Germline micronuclear genome
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Engineered macronuclear genome
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Genome Reorganization and Information

• Before any assessment can be made concerning the
  information generating aspects of genome
  rearrangements (like those seen in ciliates), two
  factors must be considered
• Genomic prerequisites
• Morphogenetic prerequisites

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Genome Reorganization and Information

• Genomic prerequisites
• X x1, x2,, xn where xi ? X is a sequence
  module and X ? G, where G is the (haploid) genome
• Y x1x1, x1x2,, xnxn where xixi yj where
  yj ? Y is a sequence module combination and Y ? G
  
• Generative rule ?(X) Y where the rule is a
  recombinational algorithm

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Back to Cubopolis

• Going back to the world of cubicles,
• X is the set of components (chairs,
• desks, partitions, etc.) that can be
• reorganized.

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Back to Cubopolis

• Y is the set of cubicle
• arrangements that can be
• generated given the
• components available.

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Back to Cubopolis

• And ? is the organization plan used to reorganize
  the cubicles.

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Genome Reorganization and Information

• A simple example
• Phage CTXphi encodes the cholera toxin and
  integrate specifically into dif-like sites in the
  Vibrio cholerae genome.
• This is mediated by the host-encoded XerCD
  recombinases.

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Genome Reorganization and Information
,
G AGGTTCAAGGATTACGACTTGGCATGCCGATTACGGCA
X
,
Phage CTXphi
?
XerCD (recombinase)
G AGGTTCAAGGATTACG
ACTTGGCATGCCGATTACGG
CA
Y
Phage CTXphi
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Genome Reorganization and Information

• 1st trivial observation The modified genome
  Vibrio cholerae genome G is clearly a derivative
  of the generative rule ?(X).
• This means that the possible sequence
  rearrangements given ? and X are informationally
  latent within ?(X).

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Genome Reorganization and Information

• That is, in cubopolis terms, the information
  for various cubicle arrangements is embedded in
  the various blueprints at hand.

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Genome Reorganization and Information

• 2nd trivial observation The generative rule ?(X)
  can range from being crisp (where any y is highly
  specific) to being fuzzy (where a number of
  mutational outcomes are possible).

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Genome Reorganization and Information

• Again, from the standpoint of cubicles, the
  blueprints and how they are executed can range
  from precision to rather shoddy.

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Genome Reorganization and Information
CAA
X
AAA
TAA
CCA
GGA
GAA
?(X)
An example of a crisp generative rule
Y
TAATAATAATAATAATAATAATAATAA
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Genome Reorganization and Information
CAA
X
AAA
TAA
CCA
GGA
GAA
?(X)
An example of a moderately crisp generative rule
Y
TAACAATAATAATAACAACAATAATAA
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Genome Reorganization and Information
CAA
X
AAA
TAA
CCA
GGA
GAA
?(X)
An example of a fuzzy generative rule
Y
TAACAA(TAA)nCAACAA
GGACCA(CAA)nAAATAA
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Genome Reorganization and Information

• Implication (1)
• If Y is small because ? is highly specific or X
  has few
• sequence modules, then the same ys will arise
  repeatedly.
• Genomic changes will be nonrandom (focused) and ?
• will be inferred.

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Genome Reorganization and Information

• Implication (2)
• But if Y is large because X has many sequence
  modules and/or ? is
• fuzzy (as with LINE and SINE integration in
  eukaryotic genomes),
• then, temporally, the appearance of any y ? Y
  will appear to be an
• evolutionarily novel event provided no
  consideration is given
• to ? or X.
• New genomic information will seem to have been
  generated by accident.

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Genome Reorganization and Information
In the strict sense then, any mutational result y
is not novel except in the trivial temporal
sense if any generative rule ? is operative,
regardless of the size of sets X and Y.
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Genome Reorganization and Information

• Phenotypic prerequisites
• 3rd trivial observation Any derivative yj ? Y
  can be termed a specification iff
• ? yj ? zj,
• where zj, a phenotypic role, is a member of Z,
  the set of intracellular component-relations, and
  ? is a higher-order generative rule.

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Genome Reorganization and Information

• Cubopolis meaning
• We can rearrange cubicles over and over again,
  but unless the different layouts have some
  higher-order system to interpret them (such as a
  staff to work there), then the process is without
  any significance.

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Genome Reorganization and Information

• Implication (3)
• Genomic changes (regardless of their mode of
  generation) only result in phenotypic changes in
  the context of a morphogenetic system.
• Genomic changes that cannot be read by the
  morphogenetic system are not informational,
  irrespective of their novelty.

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Genome Reorganization and Information
Control-element factor
Phage-binding factor
Promoter-binding factor
G AGGTTCAAGGATTAC
ACTTG
Operon
Phage CTXphi
Phage CTXphi
?
Control element
Promoter
Altered operon expression
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Genome Reorganization and Information
Genoptypic level
GATA
?
acgtGATA(GATA)nGATCGATAtttt
GATC
?
G
?
GATA-Protein
GATAGATAGATAGATA
Heterochromatin
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Genome Reorganization and Information

• At a minimum then, two things are required for
  the emergence of new
• phylogenetic information
• open-ended genomic change (i.e., mutations
  giving rise to
• information not latent or compressed in the
  system), with
• the novel mutation(s) expanding the phenotypic
  range of
• the population bearing the new genotype.

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Genome Reorganization and Information

• 1. Change (mutation) in set X
• x1 ? x1

• If (e.g.) the set X (N)3 where N can be A, C,
  G, or T, the 64 possibilities are already
  contained in X (mutation will just convert one
  module into another).
• If X is small (say with two modules, AAA and
  AAT), then a mutation AAT ? AAC will be
  informative depending on ? and ?.

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Genome Reorganization and Information

• Set enlargement again will be informative
  depending on ? and ?.
• Ditto

• Enlargement of set X.
• Both 1 and 2.

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Genome Reorganization and Information

• 4. Change in generative rule ?.

• If the change is from a fuzzier rule to a crisper
  one, then the mutational spectra will be
  diminished (no information increase).
• If the modification is from crisp to fuzzier,
  information will possibly increase.
• Regardless of the change, ? is the final arbiter
  of genomic information content.

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Genome Reorganization and Information

• If the modification is from crisp to fuzzier,
  information will possibly increase.
• Regardless of the change, ? is the final arbiter
  of genomic information content.

• 5. Change in generative rule ?.

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Genome Reorganization and Information

• Strong conclusions
• Genomic rearrangements make explicit information
  that is implicit in the genetic system (vide
  Caporale, 2003).
• Regardless of whether genomic change occurs
  through highly constrained (programmed)
  modifications or seemingly random mutations, it
  is the morphogenetic system that determines if,
  how, and when explicit information is expressed.
• Evolutionary novelty, then, must be entailed by
  generative rules.
• But if novelty is entailed by a morphogenetic
  system, how can it can be novel in any real
  sense?