Investigating Bias in Protein Properties Inferred via Ancestral Sequence Reconstruction
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Date
2017
Authors
Rickett, Abraham "Bram" James
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Ancestral Sequence Reconstruction (ASR) is a powerful technique used by researchers to study ancient proteins and their evolution. It is, however, an approximation based on incomplete information and simplifying assumptions about the evolutionary process. It is therefore important to understand and control sources of error in ASR studies. One possible source of error is electrostatics. We formulate and analyze the electrostatics of 14 distinct protein families, each containing PDB structures of reconstructed ancestral proteins and their modern descendants We observe electrostatic abnormalities in some ancestral families, however these abnormalities are not statistically significant in the context of the entire sample. Simulated evolution analyses suggest that reconstruction can generate sequences with less extreme electrostatic character compared to the known original sequence. High charge optimality is not easily recoverable through posterior probability sampling. Existence of electrostatic bias is ultimately not disproven, and should be explored further with larger samples and more rigorous analytical methods.
Description
49 pages. A thesis presented to the Department of Chemistry & Biochemistry and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science, Spring 2017
Keywords
Protein, Electrostatics, Reconstruction, Ancestral, Evolution, Bias