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On the evolution of microbes: the evolution of genomes with respect to RNA folding

Brower-Sinning, Rachel (2011) On the evolution of microbes: the evolution of genomes with respect to RNA folding. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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We hypothesized that the stringency by which RNA folds (summarized in our analysis by the predicted folding free energy (FFE)) may be under selective pressure, presumably due to its role in (reverse) transcription and translation, and its potential effect on the RNA degradation rate. For bacteria, the RNA folding will depend on the physical properties of their environment. For viruses, this balance needs to be reached for every host the virus is successfully replicated in, and may play a critical role in adapting to new hosts.
In the influenza A virus, we have shown that the FFE of its polymerase genes is evolving through time from lower to higher values, every time an avian segment jumps into humans. We postulated that this may be related to the difference in body temperature between humans and birds, as generally the genes isolated from avian sources have significantly lower FFE than the human isolates.
Furthermore, we can use the FFE and amino acid sequence of the influenza A virus, to classify whether a given virus is similar to others that can jump to and successfully infect human hosts.
In bacteria, we have shown that, consistent with previous studies of GC content, tRNA FFE is linearly correlated with growth temperature; while mRNA FFE is not. Regardless, we showed that the growth conditions are related to mRNA FFE distributions and function. Furthermore, there is a relation between mRNA FFE and half-life. Finally, we showed that gene expression can be predicted from RNA structure and sequence properties.
In studying RNA folding in both viruses and bacteria, we were able to view the possible association between FFE and environment in two ways: the number of bacterial genomes sequenced allows us to get a sense of what RNA structures and folding energies are required for the bacteria to inhabit a wide variety of environments- everything from the human body to colonizing black smokers on the ocean floor; while the number of influenza A genomes sequenced allows us to determine how the RNA structures change over time. By using both sets of information, we can get a clearer picture of both the importance of RNA structure, and how RNA structure and folding energy evolve as the host environment changes.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Brower-Sinning, Rachelrab71@pitt.eduRAB71
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBenos, Panayiotis V.benos@pitt.eduBENOS
Ross, Ted M.tmr15@pitt.eduTMR15
Zukerman, Daniel M.ddmmzz@pitt.eduDDMMZZ
Date: 19 December 2011
Date Type: Publication
Defense Date: 31 October 2011
Approval Date: 19 December 2011
Submission Date: 5 December 2011
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 221
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Computational Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: genomics, RNA folding, influenza A,
Date Deposited: 19 Dec 2011 20:03
Last Modified: 15 Nov 2016 13:55


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