dc.contributor.advisor | Wyckoff, Gerald J. | |
dc.contributor.author | Likins, Lee | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017 Summer | |
dc.description | Title from PDF of title page viewed august 6, 2017 | |
dc.description | Dissertation advisor: Gerald J. Wyckoff | |
dc.description | Vita | |
dc.description | Includes bibliographical references (pages 132-150) | |
dc.description | Thesis (Ph.D.)--School of Biological Sciences. University of Missouri--Kansas City, 2017 | |
dc.description.abstract | With the advent of sophisticated genetic, biophysical and in silico technology an
enormous amount of information is being generated regarding the structural, biochemical and
physiological aspects of proteins. Tertiary protein structural domains are assumed to be features
of proteins whose bio-historical relationships can be traceable over relevant evolutionary space.
The phylogenetics of protein domains, including their genesis, duplication, combination,
selectively derived loss and potential horizontal capture to derive novel functional
rearrangements, are of great interest to molecular evolutionists. Evolutionary and bioinformatic
analyses of a considerable collection of variable protein primary, secondary, tertiary, quaternary
and biochemical structures has established the principle that, from a functional perspective,
many, if not most, proteins are evolutionarily dependent on the functional capacity of readily
defined and identifiable, globular components defined as "domains". Therefore, it is reasonable
to infer that specific secondary and tertiary folds, or arrangements, represent functional
phenotypic characters that can be analyzed to provide insights into the evolutionary history of
any given protein domain. The evolution of proteins, at the domain level, has a significant impact
on the overall functionality of metabolic pathways in general. Therefore, insights into the
evolutionary trajectories of protein domains have the potential to inform the understanding of
every aspect in which any given protein has a role of functional significance including, but
certainly not limited to basic metabolic equilibrium, potential physical compromise at the
phenotypic level, and deeper insights into corruptions that often lead to metabolic dysfunction
and potential progression to full blown disease states. The prime focus of this study is to
investigate the evolutionary relationships of proteins, across all Kingdoms of life, that contain
within their tertiary phenotypic structure the 4-bladed β-propeller domain (the "Hemopexin" or
"PEX" domain), towards illuminating the biophysical and biochemical significance of this
specific domain's impact on protein functionality. While the phylogenetic relationships of entire
proteins that have PEX domains is relatively straight forward, the mutational accumulation in
gene sequences that lead to the tertiary structure of the PEX domain itself seems to have partially,
if not entirely, obscured the evolutionary history at the domain level.
The phylogenetic analyses presented here allow for several novel conclusions. First, this
research demonstrates that a derived primary amino acid sequence in mammalian Hemopexin
proteins (the JEN-14 epitope) represents a functional synapomorphy at the molecular level.
Secondly, that there is substantial evidence for horizontal gene transfer of PEX domain proteins
into specific Fungi. Additionally, there are no proteins containing a PEX domain in Kingdom
Archaea. Lastly, it argues that the PEX domain itself represents an evolutionary “spandrel”
(sensu Gould and Lewontin) with specifically derived functions existing around a core, preserved
structural architecture. | eng |
dc.description.tableofcontents | Structural analyses of the hemopexin protein as a means to infer the evolution of functionality between the PEX domain containing proteins -- Discovery and characterization of the JEN-14 epitope as a molecular synapomorphy in hemopexin -- Phylogenomic analyses provide insights into patterns of functional diversity between PEX domain containing proteins -- Discussion and conclusions of results from chapters 1-4 -- Determination of the tertiary structure of the PEX domain in the human proteoglycan-4 (lubricin) protein -- Evolutionary analyses of target genes identified as potential genetic markers of complications associated with diet-induced obesity -- Appendix A. Supplemental information on a 4-bladed β-propeller domain containing proteins -- Appendix B. List of the human MMPs included in the phylogenies along with a brief description of known functionality -- Appendix C. Primary sequence identity between various PEX domains: HPX, MMPs, PRG4, VTN -- Appendix D. Primary sequence and homology model of the protein limunectin from horseshoe crab -- Appendix E.PRG4 - PEX-domain DNA nucleotide sequence (shown as condons) used for ordering of the Gblock for cloning, expression and purification -- Appendix F. pET-44a-c(+) vector map -- Appendix G. Return of results from MU-DNA LIMS sequencing facility submission of sample from colony 8 from PC of transformed ligation products of the PRG4 PEX domain pET44 construct -- Appendix H. Analyses from mass spectrometry on PRG4 PEX-domain -- Appendix I. Sequence alignments for the Atp 1a3 protein in primates rooted with murines -- Appendix J. Accession numbers for all proteins used in phylogenetic and/or statistical analyses | |
dc.format.extent | xv, 152 pages | |
dc.identifier.uri | https://hdl.handle.net/10355/61496 | |
dc.publisher | University of Missouri--Kansas City | eng |
dc.subject.lcsh | Proteins -- Structure | |
dc.subject.other | Dissertation -- University of Missouri--Kansas City -- Biology | |
dc.title | Hyper-Plastic Structural Evolution Of The PEX Domain - A Model Of Evolutionary Exaptation And Neofunctionalization At The Molecular Level | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Molecular Biology and Biochemistry (UMKC) | |
thesis.degree.discipline | Cell Biology and Biophysics (UMKC) | |
thesis.degree.grantor | University of Missouri--Kansas City | |
thesis.degree.level | Doctoral | |
thesis.degree.name | Ph.D. | |