Transcript Robustness
Robustness mechanisms
in biology
Rüdiger W. Brause
Introduction
Robustness, NOT evolvability or stability
for
disturbances in ecosystems
cell response to environmental or genetic change
computer performance at input errors, disk failures,
network overload
resilience of a political institution during societal flux
viability of a technological product in wildly changing
markets
Robustness = aspect of structural network stability
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R.Brause: Nature-inspired Robustness
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What is biological robustness ?
DEF
small variances of a state
Hermisson, Wagner 2005
health, fitness, phenotype
against changes in underlying working conditions
toxic conditions, mutations, environment changes,…
compared to variance of other states to the same
changes.
Different from pure
Adaptivity
turning to a desired state
Structural stability
param. changes lead to another
structure with same behavior
NiSIS Workshop, Mallorca 2006
R.Brause: Nature-inspired Robustness
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Phenotypic robustness
Principles
Canalization
Phenotype development in multi-hill fitness landscape:
Only path (channel) with best fitness is taken. Here,
phenotypic change by landscape change stays small.
(Precondition: genetic variance).
Evolutionary neutrality
Huge phenotype differences, but small fitness
differences: no evolutionary selection.
(e.g. electrophoretic data variance of species)
NiSIS Workshop, Mallorca 2006
R.Brause: Nature-inspired Robustness
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Molecular mechanisms
Redundancy
Paralogues copies of molecules: function promote
doubling does not double effect concentrations, e.g.
transcription factors
signal transduction proteins,
metabolic pathway genes
genes encoding antibody peptides
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R.Brause: Nature-inspired Robustness
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Molecular mechanisms
Counter-effect of multiple copies: molecular costs are
too high for fast replication & translation, e.g. viruses,
bacteria.
Anti-Redundancy
suppression of deleterious variance
high redundancy accumulation of deleterious
mutations (Muller‘s ratchet) !
AR-mechanisms needed for robustness !
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Suppression of bad mutations
Mutation repair and buffering
Repair mechanism types for unreliable DNA copy
Excision repair: removing damaged regions
Direct repair:
reversal of nucleotide damage
Codon repair:
code units of messenger mRNA sequence
on transfer tRNA recognized.
Mismatch repair: replacing non-complementary bases on double
helix strands
In case of nonsense codons, tRNA suppressed.
Nonsense-mediated mRNA decay:
mRNA is supervised in cell by NMD.
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Suppression of bad mutations
Mutation repair and buffering (cont.)
Checkpoint genes in eukaryotes (kernel based cells) e.g. p53
Stop cell development until all damage is repaired:
concentration of p53 high in cells with high err. product
concentration. Trigger DNA repair on threshold overshooting.
Damage too high: p53, TNF triggers cell death (apoptosis)
Imprinting
masking of gene mutations (buffering) by
comparing DNA strings methylation of differences (MIP)
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R.Brause: Nature-inspired Robustness
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Suppression of bad mutations
Mutation result repair and buffering
Protein quality control by chaperons
Checking of passing proteins, endoplasmic reticulum-induced protein
degradation: no accumulation of unfolded proteins.
Autophagy
breaking and recycling of translated protein products of oncogenes
by overexpression of the beclin gene
Dominance modifiers
dominant genes correct influence of defective genes on enzymatic
pathways.
Main reason for alleles of diploid organisms to cause no phenotypic
effects.
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Suppression of bad mutations
Mutation result enhancement
Enhancement of damages phenotypic differences
natural selection
by
Accumulation of errors in long living cells:
programmed cell death for long living individuals
by telomere chromosome caps
loss of key error repair genes (mitochondria)
NiSIS Workshop, Mallorca 2006
R.Brause: Nature-inspired Robustness
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Robustness by statistics
codon bias
codon = (c1,c2,c3) with ci {A,G,C,T}, 43 = 64 codons possible.
Only 20 amino acids ex. redundancy with pdf of nucleotides.
But: pdf typical for species,
uniform pdf of mutations can be eliminated.
genetic bottleneck
generation transformation
diploid haploid diploid
enables strip off of deleterious mutations.
Good for small populations (small offspring, small selection).
Large populations: no bottleneck needed (bacteria, viruses).
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R.Brause: Nature-inspired Robustness
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Conclusion
Robustness in biology is achieved by different
mechanisms.
Redundancy is used, like in technical systems.
But Anti-redundancy is also necessary, to get rid of
hidden (buffered) bad mutations
Different organisms have different molecular
mechanisms, dependent on their complexity and
offspring mechanisms.
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R.Brause: Nature-inspired Robustness
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