Related papers: Strong Selection Significantly Increases Epistatic…
Background: The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to…
In this work we employ various methods of analysis (unfolding simulations and comparative analysis of structures and sequences of proteomes of thermophilic organisms) to show that organisms can follow two major strategies of thermophilic…
The Saccharomyces cerevisiae protein-protein interaction map, as well as many natural and man-made networks, shares the scale-free topology. The preferential attachment model was suggested as a generic network evolution model that yields…
An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a…
Drug resistance remains a major problem for the treatment of HIV. Resistance can occur due to mutations that were present before treatment starts or due to mutations that occur during treatment. The relative importance of these two sources…
Identifying and quantifying the benefits of sex and recombination is a long standing problem in evolutionary theory. In particular, contradictory claims have been made about the existence of a benefit of recombination on high dimensional…
Human pathogens transmitted through environmental pathways are subject to stress and pressures outside of the host. These pressures may cause pathogen pathovars to diverge in their environmental persistence and their infectivity on an…
The factors that influence genetic architecture shape the structure of the fitness landscape, and therefore play a large role in the evolutionary dynamics. Here the NK model is used to investigate how epistasis and pleiotropy -- key…
The outcomes of evolution are determined by which mutations occur and fix. In rapidly adapting microbial populations, this process is particularly hard to predict because lineages with different beneficial mutations often spread…
The genotype-fitness map plays a fundamental role in shaping the dynamics of evolution. However, it is difficult to directly measure a fitness landscape in practice, because the number of possible genotypes is astronomical. One approach is…
The fitness landscape defines the relationship between genotypes and fitness in a given environment, and underlies fundamental quantities such as the distribution of selection coefficient, or the magnitude and type of epistasis. A better…
Expression level is known to be a strong determinant of a protein's rate of evolution. But the converse can also be true: evolutionary dynamics can affect expression levels of proteins. Having implications in both directions fosters the…
The structure of molecular networks derives from dynamical processes on evolutionary time scales. For protein interaction networks, global statistical features of their structure can now be inferred consistently from several…
How do living cells achieve sufficient abundances of functional protein complexes while minimizing promiscuous non-functional interactions? Here we study this problem using a first-principle model of the cell whose phenotypic traits are…
The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, e.g., of central importance for our understanding of the phenotypic effect of mutations related to…
A central question is how the conformational changes of proteins affect their function and the inhibition of this function by drug molecules. Many enzymes change from an open to a closed conformation upon binding of substrate or inhibitor…
Hysteresis and bet-hedging (random choice of phenotypes) are two different observations typically linked with multiplicity of phenotypes in biological systems. Hysteresis can be viewed as form of the system's persistent memory of past…
Epigenetics plays a key role in cellular differentiation and maintaining cell identity, enabling cells to regulate their genetic activity without altering the DNA sequence. Epigenetic regulation occurs within the context of hierarchically…
Gene-environment interactions have important implications to elucidate the genetic basis of complex diseases beyond the joint function of multiple genetic factors and their interactions (or epistasis). In the past, G$\times$E interactions…
Protein-protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions and structural biology has provided detailed functional insight for select 3D protein…