Related papers: Factors controlling protein evolvability, at the m…
In epistatic fitness landscapes, the fitness effect of a mutation depends on the genetic background and may even switch between deleterious and beneficial depending on the presence of another mutation. Epistatic interactions may cause both…
A central question in developmental biology is how size and position are determined. The genetic code carries instructions on how to control these properties in order to regulate the pattern and morphology of structures in the developing…
Biases in molecular evolution can significantly influence evolutionary trajectories. They have been described in a variety of contexts such as development and mutation, but not for acquiring new functions (i.e. emergence). Here, we…
Biological evolution continuously refines the design of species, resulting in highly optimised organisms over hundreds of millennia. Intuitively, we expect that random changes-evolution's primary mechanism-are more likely to be harmful than…
Our understanding of evolution is shaped strongly by how we conceive of its fundamental causes. In the original Modern Synthesis, evolution was defined as a process of shifting the frequencies of available alleles at many loci affecting a…
Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…
Epistasis occurs when the effect of a mutation depends on its carrier's genetic background. Despite increasing evidence that epistasis for fitness is common, its role during evolution is contentious. Fitness landscapes, mappings of genotype…
These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…
Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the probability of multi-mutation leaps, that is, several mutations…
Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…
Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein to occupy, leaving open the question of what controls the emergence of these distinct…
The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated…
Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is…
The evolutionary origins of ageing and age-associated diseases continue to pose a fundamental question in biology. This study is concerned with a recently proposed framework, which conceptualises development and ageing as a continuous…
The diversity and quality of natural systems have been a puzzle and inspiration for communities studying artificial life. It is now widely admitted that the adaptation mechanisms enabling these properties are largely influenced by the…
Constraints on changes in expression levels across all cell components imposed by the steady growth of cells have recently been discussed both experimentally and theoretically. By assuming a small environmental perturbation and considering…
Evolution has fascinated quantitative and physical scientists for decades: how can the random process of mutation, recombination, and duplication of genetic information generate the diversity of life? What determines the rate of evolution?…
If evolution can be connected to the principle of least action, and if it is depicted in evolution space versus time then it corresponds to the direction of ultimate causation. As an organism evolves and follows a path of proximate…
During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous…
Acidosis in tumors arises from reprogrammed metabolism and compromised vasculature, creating a harsh, acidic microenvironment that drives the evolutionary selection of acid-resistant cell phenotypes. A mathematical model is proposed to…