Simulation of protein evolution by random fixation of allowed codons

Area of Science:

• Molecular Evolution
• Computational Biology
• Genetics

Background:

• Protein evolution simulation relies on models like random fixation of allowed codons (RFAC).
• RFAC simulates nucleotide substitutions in DNA, fixing synonymous mutations for allowed amino acids.
• This model aligns with the neutral theory of molecular evolution, allowing for multiple fixations and back mutations.

Purpose of the Study:

• To test the neutral theory of molecular evolution through computer simulation.
• To compare RFAC simulation results with empirical evolutionary data for specific proteins.
• To identify sources of discrepancy between simulated and real protein evolution.

Main Methods:

• Utilized the random fixation of allowed codons (RFAC) model for DNA sequence simulation.
• Incorporated a phylogenetic approach based on the fossil record.
• Compared simulation outcomes with real evolutionary data for fibrinopeptides A, cytochromes C, and hemoglobin chains.

Main Results:

• Simulated and real evolutionary rates showed some agreement, particularly for fibrinopeptides A and cytochromes C.
• Fixation rates in simulations ranged from 2.4 x 10^-10 to 10^-8 accepted nucleotide fixations per codon per year.
• The primary cause of disagreement was the irregular rates observed in real biological evolution.

Conclusions:

• The RFAC model provides a test of the neutral theory of molecular evolution.
• While RFAC simulation approximates real evolution, irregularities in natural evolutionary rates limit precise concordance.
• Further comparisons were made with other evolutionary models like REH, augmented maximum parsimony, and PAM.