As organisms evolve, the effects of mutations change as a result of epistatic interactions with
other mutations accumulated along the line of descent. This can lead to shifts in adaptability …

The genotype–fitness map (that is, the fitness landscape) is a key determinant of evolution,
yet it has mostly been used as a superficial metaphor because we know little about its …

Evolutionary changes in organismal traits may occur either gradually or suddenly. However,
until recently, there has been little direct information about how phenotypic changes are …

Substantial improvements in enzyme activity demand multiple mutations at spatially
proximal positions in the active site. Such mutations, however, often exhibit unpredictable …

The evolution of antibiotic resistance carries a fitness cost, expressed in terms of reduced
competitive ability in the absence of antibiotics. This cost plays a key role in the dynamics of …

The main forces directing long-term molecular evolution remain obscure. A sizable fraction
of amino-acid substitutions seem to be fixed by positive selection,,,, but it is unclear to what …

Recent years have witnessed an explosion of interest in understanding the role of
conformational dynamics both in the evolution of new enzymatic activities from existing …

There has been much debate about the extent to which mutational epistasis, that is, the
dependence of the outcome of a mutation on the genetic background, constrains …

The concept of a fitness landscape is a powerful metaphor that offers insight into various
aspects of evolutionary processes and guidance for the study of evolution. Until recently …

Proteins are molecular machines composed of complex, highly connected amino acid
networks. Their functional optimization requires the reorganization of these intramolecular …