Huang, W., Petrosino, J., Hirsch, M., Shenkin, P. Protein tolerance to random amino acid change. Searching sequence space for protein catalysts. Towards a covering set of protein family profiles. Deciphering the message in protein sequences: tolerance to amino acid substitutions. How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. The structure of the protein universe and genome evolution. Empirical fitness landscapes reveal accessible evolutionary paths. Darwinian evolution can follow only very few mutational paths to fitter proteins. Perspective: sign epistasis and genetic constraint on evolutionary trajectories. Dobzhansky-Muller incompatibilities in protein evolution. Multidimensional epistasis and the disadvantage of sex. Natural selection and the concept of a protein space. Protein superfamily evolution and the last universal common ancestor (LUCA). Comparative genomics, minimal gene-sets and the last universal common ancestor.
Algorithms for computing parsimonious evolutionary scenarios for genome evolution, the last universal common ancestor and dominance of horizontal gene transfer in the evolution of prokaryotes. Stability effects of mutations and protein evolvability. Genetic constraints on protein evolution. Missense meanderings in sequence space: a biophysical view of protein evolution. Trends in protein evolution inferred from sequence and structure analysis. Thus, ∼3.5 × 10 9 yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.Īravind, L., Mazumder, R., Vasudevan, S. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: ∼98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. Here we explore the limits of protein evolution using sequence divergence data. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions 1, 2, 3, 4.