102 research outputs found
The Freezing of Random RNA
We study secondary structures of random RNA molecules by means of a
renormalized field theory based on an expansion in the sequence disorder. We
show that there is a continuous phase transition from a molten phase at higher
temperatures to a low-temperature glass phase. The primary freezing occurs
above the critical temperature, with local islands of stable folds forming
within the molten phase. The size of these islands defines the correlation
length of the transition. Our results include critical exponents at the
transition and in the glass phase.Comment: 4 pages, 8 figures. v2: presentation improve
Multiple Crossover Phenomena and Scale Hopping in Two Dimensions
We study the renormalization group for nearly marginal perturbations of a
minimal conformal field theory M_p with p >> 1. To leading order in
perturbation theory, we find a unique one-parameter family of ``hopping
trajectories'' that is characterized by a staircase-like renormalization group
flow of the C-function and the anomalous dimensions and that is related to a
recently solved factorizable scattering theory. We argue that this system is
described by interactions of the form t phi_{(1,3)} - t' \phi_{(3,1)} . As a
function of the relevant parameter t, it undergoes a phase transition with new
critical exponents simultaneously governed by all fixed points M_p, M_{p-1},
..., M_3. Integrable lattice models represent different phases of the same
integrable system that are distinguished by the sign of the irrelevant
parameter t'.Comment: 20 pages, 5 figure
Adaptive evolution of transcription factor binding sites
The regulation of a gene depends on the binding of transcription factors to
specific sites located in the regulatory region of the gene. The generation of
these binding sites and of cooperativity between them are essential building
blocks in the evolution of complex regulatory networks. We study a theoretical
model for the sequence evolution of binding sites by point mutations. The
approach is based on biophysical models for the binding of transcription
factors to DNA. Hence we derive empirically grounded fitness landscapes, which
enter a population genetics model including mutations, genetic drift, and
selection. We show that the selection for factor binding generically leads to
specific correlations between nucleotide frequencies at different positions of
a binding site. We demonstrate the possibility of rapid adaptive evolution
generating a new binding site for a given transcription factor by point
mutations. The evolutionary time required is estimated in terms of the neutral
(background) mutation rate, the selection coefficient, and the effective
population size. The efficiency of binding site formation is seen to depend on
two joint conditions: the binding site motif must be short enough and the
promoter region must be long enough. These constraints on promoter architecture
are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive
evolution of genetic switches and of signal integration through binding
cooperativity between different sites. Experimental tests of this picture
involving the statistics of polymorphisms and phylogenies of sites are
discussed.Comment: published versio
Universality and predictability in molecular quantitative genetics
Molecular traits, such as gene expression levels or protein binding
affinities, are increasingly accessible to quantitative measurement by modern
high-throughput techniques. Such traits measure molecular functions and, from
an evolutionary point of view, are important as targets of natural selection.
We review recent developments in evolutionary theory and experiments that are
expected to become building blocks of a quantitative genetics of molecular
traits. We focus on universal evolutionary characteristics: these are largely
independent of a trait's genetic basis, which is often at least partially
unknown. We show that universal measurements can be used to infer selection on
a quantitative trait, which determines its evolutionary mode of conservation or
adaptation. Furthermore, universality is closely linked to predictability of
trait evolution across lineages. We argue that universal trait statistics
extends over a range of cellular scales and opens new avenues of quantitative
evolutionary systems biology
Rate and cost of adaptation in the Drosophila Genome
Recent studies have consistently inferred high rates of adaptive molecular
evolution between Drosophila species. At the same time, the Drosophila genome
evolves under different rates of recombination, which results in partial
genetic linkage between alleles at neighboring genomic loci. Here we analyze
how linkage correlations affect adaptive evolution. We develop a new inference
method for adaptation that takes into account the effect on an allele at a
focal site caused by neighboring deleterious alleles (background selection) and
by neighboring adaptive substitutions (hitchhiking). Using complete genome
sequence data and fine-scale recombination maps, we infer a highly
heterogeneous scenario of adaptation in Drosophila. In high-recombining
regions, about 50% of all amino acid substitutions are adaptive, together with
about 20% of all substitutions in proximal intergenic regions. In
low-recombining regions, only a small fraction of the amino acid substitutions
are adaptive, while hitchhiking accounts for the majority of these changes.
Hitchhiking of deleterious alleles generates a substantial collateral cost of
adaptation, leading to a fitness decline of about 30/2N per gene and per
million years in the lowest-recombining regions. Our results show how
recombination shapes rate and efficacy of the adaptive dynamics in eukaryotic
genomes
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