University of Texas – Austin
Laurent, Jon Michael.
Evolutionary conservation of protein abundance and function.
Degree: PhD, Cellular and Molecular Biology, 2016, University of Texas – Austin
Conservation lies at the heart of biology. All organisms on earth are descended from a common ancestor, resulting in the preservation of many biological properties, from genotype to gene function and phenotype. The advent of next generation nucleic acid sequencing, mass-spectrometry proteomics, and other global measurement technologies, along with the emergence of computational and systems biology, have facilitated huge strides in our ability to make meaningful observations at all levels of biological phenomena. As a result, we can now make comparative assessments of the degree to which various processes are conserved and connected between species. Additionally, newly developed techniques for highly efficient genome manipulation enable us to test these comparative observations experimentally.
As an example, global measurement technologies have enabled observation of the abundances of nearly all proteins and mRNAs in the cells in many organisms, and further determine to what extent proteins levels are controlled by the levels of mRNA. In chapter one, I utilize these data to investigate the conservation of protein and mRNA abundance levels across a diverse set of organisms. Expression levels, while important for proper cell functioning, are only one observable property between genotype and phenotype. Evolutionary conservation can be seen all the way to phenotype, as in the identification of orthologous phenotypes, or ‘phenologs’, described in further detail in the introduction. Given these conserved phenomena, we asked a simple question: ’To what extent can an organisms genes function in the context of another organism?’. To address this question, we systematically replaced hundreds of yeast genes with their human orthologs. In chapters
two and three I present these replacements, and further discuss what features of the genes or ortholog groups can explain their ability to replace or not. Chapter four includes a presentation of an ongoing effort to extend the replacement studies by replacing a complete yeast protein complex with its human counterpart. I will end with a discussion of the current state of relevant work, and where I see additional efforts going into the future.
Advisors/Committee Members: Marcotte, Edward M. (advisor), Ellington, Andrew D (committee member), Iyer, Vishwanath R (committee member), Browning, Karen S (committee member), Appling, Dean R (committee member).
Subjects/Keywords: Humanization; Yeast genetics; Systems biology; Humanized yeast
to Zotero / EndNote / Reference
APA (6th Edition):
Laurent, J. M. (2016). Evolutionary conservation of protein abundance and function. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/68224
Chicago Manual of Style (16th Edition):
Laurent, Jon Michael. “Evolutionary conservation of protein abundance and function.” 2016. Doctoral Dissertation, University of Texas – Austin. Accessed January 20, 2021.
MLA Handbook (7th Edition):
Laurent, Jon Michael. “Evolutionary conservation of protein abundance and function.” 2016. Web. 20 Jan 2021.
Laurent JM. Evolutionary conservation of protein abundance and function. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2016. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2152/68224.
Council of Science Editors:
Laurent JM. Evolutionary conservation of protein abundance and function. [Doctoral Dissertation]. University of Texas – Austin; 2016. Available from: http://hdl.handle.net/2152/68224