Modeling Protein Evolution - Computational Modeling of Biological Systems - page 317

the binding partner changes, allowing us to model evolutionary dynamics under
changing selective constraints. When fitness involves the binding of multiple
proteins, we can consider these interacting proteins as encoded in a single
genome. The proteins would then co-evolve as the genome evolves.

The above selective constraints refer to the properties of the amino acid sequence
that constitute the protein. Mutations, however, occur at the DNA level, and it
is only through the process of translation that these changes are represented at
the amino acid level [ 21 ]. The accuracy of translation is much lower than that of
DNA replication, meaning that there will be a distribution of protein sequences
corresponding to a single DNA sequence. This more complicated relationship
between gene and gene product, and the consequential complication of the fitness
function, can have interesting and important evolutionary consequences [ 22 - 24 ].

2.3 Modeling Evolutionary Dynamics

Evolution is a population phenomenon. In a population of individuals, mutations
that change the phenotype of the organism will succeed based on how that
phenotype fares in competition with other phenotypes that exist in the population
at the same time. A point mutation is the exchange of one nucleotide for another
somewhere in the genome. If the exchange occurs in a coding region, it might alter
the amino acid that is produced upon translation (a missense or nonsynonymous
mutation), or it might result in a stop codon, thus causing premature truncation
of the protein (a nonsense mutation). Alternatively, the new codon might encode
the same amino acid as the old codon, and thus produce no change in the
translated protein sequence (a silent or synonymous mutation). Mutations that are
synonymous are more likely to have a relatively neutral effect on fitness compared to
missense or nonsense mutations, because they do not alter the amino acid sequence
and thus do not alter the functional properties of the individual protein. More
complicated mutations are possible involving the deletion, insertion, duplication,
or re-arrangement of single nucleotides, stretches of nucleotides, or larger units of
the genome.
By definition, mutations occur in individuals, but in subsequent generations
the offspring of the mutated individual will carry the mutation and compete with
offspring in the population that do not carry the mutation. Ultimately, this will
usually lead either to elimination of the new mutation from the population or to
fixation , the process whereby the other variants in the population are eliminated.
After fixation, the previous “mutant” defines a new “wild type.”
In unusual cases, mutants may be neither eliminated nor fixed for long periods
of time, during which the population remains polymorphic. For example, in diploid
organisms an individual carries two copies of each gene, and an individual with one
copy of each variant (a heterozygote ) may have an advantage over other individuals.
This is the case with the mutation causing sickle-cell anemia, in which one copy