Representation of all possible protein/DNA/RNA sequences organised in a multidimensional space
Protein sequence space can be represented as a space with n dimensions, where n is the number of amino acids in the protein. Each axis has 20 positions representing the 20 amino acids. There are 400 possible 2 amino acid proteins (dipeptide) which can be arranged in a 2D grid. the 8000 tripeptides can be arranged in a 3D cube. Most proteins are longer than 100 amino acids and so occupy large, multidimensional spaces containing an astronomical number protein sequences.How directed evolution climbs fitness landscapes. Performing multiple rounds of directed evolution is useful not only because a new library of mutants is created in each round, but also because each new library uses better mutants as templates than the previous. The experiment is analogous to climbing a hill on a 'fitness landscape,' where elevation represents the desired property. The goal is to reach the summit, which represents the best achievable mutant. Each round of selection samples mutants on all sides of the starting template (1) and selects the mutant with the highest elevation, thereby climbing the hill. This is repeated until a local summit is reached (2).
Most sequences in sequence space have no function, leaving relatively small regions that are populated by naturally occurring genes.[5] Each protein sequence is adjacent to all other sequences that can be reached through a single mutation.[6] It has been estimated that the whole functional protein sequence space has been explored by life on the Earth.[7] Evolution by natural selection can be visualised as the process of sampling nearby sequences in sequence space and moving to any with improved fitness over the current one.
^DePristo, Mark A.; Weinreich, Daniel M.; Hartl, Daniel L. (2 August 2005). "Missense meanderings in sequence space: a biophysical view of protein evolution". Nature Reviews Genetics. 6 (9): 678–687. doi:10.1038/nrg1672. PMID16074985. S2CID13236893.