6,921 research outputs found
Predictability of evolutionary trajectories in fitness landscapes
Experimental studies on enzyme evolution show that only a small fraction of
all possible mutation trajectories are accessible to evolution. However, these
experiments deal with individual enzymes and explore a tiny part of the fitness
landscape. We report an exhaustive analysis of fitness landscapes constructed
with an off-lattice model of protein folding where fitness is equated with
robustness to misfolding. This model mimics the essential features of the
interactions between amino acids, is consistent with the key paradigms of
protein folding and reproduces the universal distribution of evolutionary rates
among orthologous proteins. We introduce mean path divergence as a quantitative
measure of the degree to which the starting and ending points determine the
path of evolution in fitness landscapes. Global measures of landscape roughness
are good predictors of path divergence in all studied landscapes: the mean path
divergence is greater in smooth landscapes than in rough ones. The
model-derived and experimental landscapes are significantly smoother than
random landscapes and resemble additive landscapes perturbed with moderate
amounts of noise; thus, these landscapes are substantially robust to mutation.
The model landscapes show a deficit of suboptimal peaks even compared with
noisy additive landscapes with similar overall roughness. We suggest that
smoothness and the substantial deficit of peaks in the fitness landscapes of
protein evolution are fundamental consequences of the physics of protein
folding.Comment: 14 pages, 7 figure
Statistical Physics of Evolutionary Trajectories on Fitness Landscapes
Random walks on multidimensional nonlinear landscapes are of interest in many
areas of science and engineering. In particular, properties of adaptive
trajectories on fitness landscapes determine population fates and thus play a
central role in evolutionary theory. The topography of fitness landscapes and
its effect on evolutionary dynamics have been extensively studied in the
literature. We will survey the current research knowledge in this field,
focusing on a recently developed systematic approach to characterizing path
lengths, mean first-passage times, and other statistics of the path ensemble.
This approach, based on general techniques from statistical physics, is
applicable to landscapes of arbitrary complexity and structure. It is
especially well-suited to quantifying the diversity of stochastic trajectories
and repeatability of evolutionary events. We demonstrate this methodology using
a biophysical model of protein evolution that describes how proteins maintain
stability while evolving new functions
Chance and Necessity in Evolution: Lessons from RNA
The relationship between sequences and secondary structures or shapes in RNA
exhibits robust statistical properties summarized by three notions: (1) the
notion of a typical shape (that among all sequences of fixed length certain
shapes are realized much more frequently than others), (2) the notion of shape
space covering (that all typical shapes are realized in a small neighborhood of
any random sequence), and (3) the notion of a neutral network (that sequences
folding into the same typical shape form networks that percolate through
sequence space). Neutral networks loosen the requirements on the mutation rate
for selection to remain effective. The original (genotypic) error threshold has
to be reformulated in terms of a phenotypic error threshold. With regard to
adaptation, neutrality has two seemingly contradictory effects: It acts as a
buffer against mutations ensuring that a phenotype is preserved. Yet it is
deeply enabling, because it permits evolutionary change to occur by allowing
the sequence context to vary silently until a single point mutation can become
phenotypically consequential. Neutrality also influences predictability of
adaptive trajectories in seemingly contradictory ways. On the one hand it
increases the uncertainty of their genotypic trace. At the same time neutrality
structures the access from one shape to another, thereby inducing a topology
among RNA shapes which permits a distinction between continuous and
discontinuous shape transformations. To the extent that adaptive trajectories
must undergo such transformations, their phenotypic trace becomes more
predictable.Comment: 37 pages, 14 figures; 1998 CNLS conference; high quality figures at
http://www.santafe.edu/~walte
Funnels in Energy Landscapes
Local minima and the saddle points separating them in the energy landscape
are known to dominate the dynamics of biopolymer folding. Here we introduce a
notion of a "folding funnel" that is concisely defined in terms of energy
minima and saddle points, while at the same time conforming to a notion of a
"folding funnel" as it is discussed in the protein folding literature.Comment: 6 pages, 3 figures, submitted to European Conference on Complex
Systems 200
Fractal geometry of spin-glass models
Stability and diversity are two key properties that living entities share
with spin glasses, where they are manifested through the breaking of the phase
space into many valleys or local minima connected by saddle points. The
topology of the phase space can be conveniently condensed into a tree
structure, akin to the biological phylogenetic trees, whose tips are the local
minima and internal nodes are the lowest-energy saddles connecting those
minima. For the infinite-range Ising spin glass with p-spin interactions, we
show that the average size-frequency distribution of saddles obeys a power law
, where w=w(s) is the number of minima that can be
connected through saddle s, and D is the fractal dimension of the phase space
Fractal geometry of spin-glass models
Stability and diversity are two key properties that living entities share
with spin glasses, where they are manifested through the breaking of the phase
space into many valleys or local minima connected by saddle points. The
topology of the phase space can be conveniently condensed into a tree
structure, akin to the biological phylogenetic trees, whose tips are the local
minima and internal nodes are the lowest-energy saddles connecting those
minima. For the infinite-range Ising spin glass with p-spin interactions, we
show that the average size-frequency distribution of saddles obeys a power law
, where w=w(s) is the number of minima that can be
connected through saddle s, and D is the fractal dimension of the phase space
Complexity of evolutionary equilibria in static fitness landscapes
A fitness landscape is a genetic space -- with two genotypes adjacent if they
differ in a single locus -- and a fitness function. Evolutionary dynamics
produce a flow on this landscape from lower fitness to higher; reaching
equilibrium only if a local fitness peak is found. I use computational
complexity to question the common assumption that evolution on static fitness
landscapes can quickly reach a local fitness peak. I do this by showing that
the popular NK model of rugged fitness landscapes is PLS-complete for K >= 2;
the reduction from Weighted 2SAT is a bijection on adaptive walks, so there are
NK fitness landscapes where every adaptive path from some vertices is of
exponential length. Alternatively -- under the standard complexity theoretic
assumption that there are problems in PLS not solvable in polynomial time --
this means that there are no evolutionary dynamics (known, or to be discovered,
and not necessarily following adaptive paths) that can converge to a local
fitness peak on all NK landscapes with K = 2. Applying results from the
analysis of simplex algorithms, I show that there exist single-peaked
landscapes with no reciprocal sign epistasis where the expected length of an
adaptive path following strong selection weak mutation dynamics is
even though an adaptive path to the optimum of length less
than n is available from every vertex. The technical results are written to be
accessible to mathematical biologists without a computer science background,
and the biological literature is summarized for the convenience of
non-biologists with the aim to open a constructive dialogue between the two
disciplines.Comment: 14 pages, 3 figure
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