Fig. 3

The “jackprot” model of protein evolution. A slot machine (lower left) represents the cellular apparatus required to generate each of the three nucleotides coding for an amino acid, for example, the starting codon methionine ATG. The probability of generating ATG in a single attempt, without the influence of natural selection, is equal to one in 64 (1/4 × 4 × 4); however, each time a biologically meaningful nucleotide is generated by the slot-machine (mimicking mutation rate), natural selection would keep it as a building block of a codon and as a partial win, or “jackdon.” Thus, the probability of arriving under selection at the ATG sequence would be equal to one in 12 (1/4 + 4 + 4). Winning the “jackprot,” or highest-fitness complete-peptide sequence, for example, 160 amino acids plus one-stop codon in the sequence of KcsA, a K⁺ channel from the bacterium Streptomyces lividans, would require gradual and cumulative smaller wins (“jackdons”) at each nucleotide position, which lead to larger rewards when a correct amino acid is generated by the slot machine (“jackacids”), and which subsequently lead to the “jackprot” or the complete 161 codons. The smaller slot machines represent each cell apparatus necessary to generate the first ten amino acids of KcsA (complete sequence available at GenBank Z37969; Swiss-Prot P0A334); the genomic sequence, letter coding/acronym, and the number of codons coding for that specific amino acid within the genetic code are shown below each machine (e.g., ATG, M met, and one in 64)