Understanding Adaptation by Elucidating the Underlying Changes in Molecular Mechanisms Association with Selection in Two-Component Response Systems.
Dr. Misty Thomas
Title: Understanding adaptation by elucidating the underlying changes in molecular mechanisms association with selection in two-component response systems. Authors: Amina Bradley, Joseph Graves, and Misty Thomas Background: Two component response systems (TCRS) are utilized by microorganisms to detect changes in the environment. This triggers a biological response such as cell division, metabolism, motility, or antibiotic resistance. TCRSs are the most commonly used mechanism by prokaryotic organisms to sense, respond, and adapt to their environment. They use a histidine kinase to sense an external stimulus and relay a message to the interior of the cell through autophosphorylation of a conserved histidine residue on the cytoplasmic domain of the protein. The histidine kinase then transfers a phosphate to a conserved aspartate residue on a response regulator, which regulates the activation or repression of transcription of specific genes. Although TCRS are the best-known system for bacterial acclimation, little is known about the role they play in adaptation. Research Question: Can phenotypic changes be predicted from genetics depending on which domain a mutation is acquired in a TCRS Hypothesis: All mutations acquired in sensor domains will be deleterious to function, thereby eliminating the protein's ability to respond and autophosphorylate. All mutations acquired in the N-terminal region or the cytoplasmic domain will give rise to a constitutively active protein. Method: We will evaluate the data in the Long-term Evolution Experiment generated by the Lenski Lab at Michigan State University using software make by the Barrick lab (UT Austin) (http://barricklab.org/shiny/LTEE-Ecoli/) for mutations in TCRS identified in the Kegg database (https://www.genome.jp/kegg-bin/show_pathway?map=ko02020&show_description=show). We will then map each of these mutations to its specific domain and make predictions in the associated changes in function. Conclusion: It is very difficult to make predictions of resultant phenotypes from genetic determinants. Since TCRS are so vital in acclimations and adaptation, being able to predict potential phenotypes from genetic material could be vital in better understanding the inhabitants of a particular environment especially in circumstances where many microbes are unculturable. Future Directions: Incorporate identified mutations in specific domains of TCRSs in Escherichia coli to see if we can obtain the phenotypic response that was predicted.
Bradley, Amina, "Understanding Adaptation by Elucidating the Underlying Changes in Molecular Mechanisms Association with Selection in Two-Component Response Systems." (2019). Undergraduate Research and Creative Inquiry Symposia. 219.