Natural selection drives evolving populations up the fitness landscape, the projection from
nucleotide sequence space to organismal reproductive success. While it has long been …

When attempting to understand evolution, we traditionally rely on analysing evolutionary
outcomes, despite the fact that unseen intermediates determine its course. A handful of …

Directed evolution can generate a remarkable range of new enzyme properties. Alternate
substrate specificities and reaction selectivities are readily accessible in enzymes from …

The fitness landscape captures the relationship between genotype and evolutionary fitness
and is a pervasive metaphor used to describe the possible evolutionary trajectories of …

Sequencing DNA from several organisms has revealed that duplication and drift of existing
genes have primarily moulded the contents of a given genome. Though the effect of …

The spread of high-level pyrimethamine resistance in Africa threatens to curtail the
therapeutic lifetime of antifolate antimalarials. We studied the possible evolutionary …

Having multiple peaks within fitness landscapes critically affects the course of evolution, but
whether their presence imposes specific requirements at the level of genetic interactions …

The effect of a mutation on the organism often depends on what other mutations are already
present in its genome. Geneticists refer to such mutational interactions as epistasis. Pairwise …

Evolutionary adaptation is often likened to climbing a hill or peak. While this process is
simple for fitness landscapes where mutations are independent, the interaction between …

Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may
fail to evolve when essential mutations are only accessible through positive selection if they …