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Author Chen, Peiqiu
Title Molecular evolution and thermal adaptation
book jacket
Descript 129 p
Note Source: Dissertation Abstracts International, Volume: 72-09, Section: B, page: 5375
Adviser: Eugene Shakhnovich
Thesis (Ph.D.)--Harvard University, 2011
In this thesis, we address problems in molecular evolution, thermal adaptation, and the kinetics of adaptation of bacteria and viruses to elevated environmental temperatures. We use a nearly neutral fitness model where the replication speed of an organism is proportional to the copy number of folded proteins. Our model reproduces the distribution of stabilities of natural proteins in excellent agreement with experiment. We find that species with high mutation rates tend to have less stable proteins compared to species with low mutation rate
We found that a broad distribution of protein stabilities observed in the model and in experiment is the key determinant of thermal response for viruses and bacteria. Our results explain most of the earlier experimental observations: striking asymmetry of thermal response curves, the absence of evolutionary trade-off which was expected but not found in experiments, correlation between denaturation temperature for several protein families and the Optimal Growth Temperature (OGT) of their carrier organisms, and proximity of bacterial or viral OGTs to their evolutionary temperatures. Our theory quantitatively and with high accuracy described thermal response curves for 35 bacterial species
The model also addresses the key to adaptation is in weak-link genes (WLG), which encode least thermodynamically stable essential proteins in the proteome. We observe, as in experiment, a two-stage adaptation process. The first stage is a Luria-Delbruck type of selection, whereby rare WLG alleles, whose proteins are more stable than WLG proteins of the majority of the population (either due to standing genetic variation or due to an early acquired mutation), rapidly rise to fixation. The second stage constitutes subsequent slow accumulation of mutations in an adapted population. As adaptation progresses, selection regime changes from positive to neutral: Selection coefficient of beneficial mutations scales as a negative power of number of generations. Diversity plays an important role in thermal adaptation: While monoclonal strains adapt via acquisition and rapid fixation of new early mutations, wild population adapt via standing genetic variations, and they are more robust against thermal shocks due to greater diversity within the initial population
School code: 0084
Host Item Dissertation Abstracts International 72-09B
Subject Physics, Theory
Biophysics, General
0753
0786
Alt Author Harvard University
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