Understanding the Lineage-Specific Amino Acid Substitution Process
November 10, Tue 2009
1:00 pm, MRB 100 Conference Room
Dr. David A. Liberles
Department of Molecular Biology, University of Wyoming
In Darwinian evolution, mutations occur approximately at random in a gene, turned into amino acid mutations by the genetic code. Some mutations are fixed to become substitutions and some are eliminated from the population. Partitioning pairs of closely related species with complete genome sequences by population size, we look at the PAM matrices generated for these partitions and compare the substitution patterns between species. A population genetic model is generated that relates the relative fixation probabilities of different types of mutations to the selective pressure and population size. Parameterizations of the average and distribution of selective pressures for different amino acid substitution types in different population size comparisons are generated using a Bayesian framework. We find that partitions in population size as well as in substitution type are required to explain the substitution data. Mechanistic explanations of this will be discussed.
To further explore the role of underlying processes in amino acid substitution, we analyzed embryophyte (plant) gene families from the TAED database, where solved structures for at least one member exist in PDB. Using PAML, branches were assigned to three categories, strong negative selection, moderate negative selection/neutrality, and positive selection. Focusing on the first and third categories, sites changing along gene family lineages were identified and the spatial patterns of ubstitution observed. Selective sweeps are expected to create primary sequence clustering under positive selection. Co-evolution through direct physical interaction is expected to cause cause tertiary structural clustering. Under positive selection, the most significant signal was found at the primary sequence level, reflecting the action of selective sweeps. However, a significant independent signal was detected at both the primary and tertiary levels. Under strong negative selection, the signals were not found to be independent. These results will also be discussed mechanistically.