Browsing by Author "Jeff Thorne, Committee Member"

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Evolutionary Inferences from Genomic Patterns of Polymorphism in Arabidopsis and Rice
(2008-01-07) Reininga, Jennifer M.; Michael Purugganan, Committee Chair; Jeff Thorne, Committee Member; Trudy Mackay, Committee Member; Jose Alonso, Committee Member
Finding homologous genes with primers designed using evolutionary models
(2004-02-22) Thompson, Denis; Henry Schaffer, Committee Chair; Jeff Thorne, Committee Member; Charlie Eugene Smith, Committee Member; Michael Purugganan, Committee Member
Genes homologous to a set of known, aligned, genes can be found by screening DNA libraries with PCR. PCR primers for such screens are commonly designed via a method described by Sells and Chernoff (1995). This standard design method does not make use of information about the evolutionary relationship between the known genes. The present study investigated the efficacy of using information about evolutionary relationships (inferred from the sequence data) in the design of PCR primers. This study compares the standard primer design method (represented herein by a modified multinomial distribution) with evolutionary model based primer design methods. The primer design method that, given an alignment of known sequences with one sequence left out, assigned a higher probability, on average, to the left-out sequence, was defined as the better method. By this measure of relative performance, an evolutionary model based primer design method sensitive to states correlated across sites of a sequence, outperformed the standard method, on the alignments studied.
Plant Molecular Evolution
(2006-08-07) Strain, Errol Alan; Jeff Thorne, Committee Member; Michael Purugganan, Committee Member; William Atchley, Committee Member; Spencer Muse, Committee Chair
The current dissertation looks at the molecular evolution of protein-coding genes in the flowering plant Arabidopsis thaliana and within two RNA viruses, humanimmunodeficiency virus (HIV) and Astroviridae. We analyzed members of the receptor-like kinase (RLK) gene family in Arabidopsis thaliana for positive selection. Likelihood analysis found evidence for positive selection in 12 of the 52 RLK family sequences groups. These 12 groups represent 97 of the 403 sequences analyzed. The majority of genes in groups subject to positive selection have not been functionally characterized, but sites under selection are predominantly located in the extracellular region. In HIV we use Akaike Information Criteria (AIC) based model averaging for models of nucleotide evolution to examine estimates of genetic distance and the ratio of transition⁄transversion (ts⁄tv). AIC weighted estimates of distance and ts/tv were shown to be robust relative to model assumptions. AIC weighted estimates of the ts⁄tv ratio in simulated HIV sequences generally had less variance than similar estimates made by selecting the single best scoring AIC model. Astroviruses are a leading cause of viral gastroenteritis in infants worldwide and little is known about the mechanisms of astrovirus-induced diarrhea or the virally encoded components responsible for disease. We report the genomic sequence of nine novel TAstV-2 isolates. Nucleotide and amino acid identities for the isolates were generally > 90% conserved. Phylogenies constructed using genomic RNA and the individual open reading frames (ORF) provide evidence for recombination and indicate differences in substitution rates between non-structural and structural genes. Analysis of the viral capsid genes using codon models of evolution indicate site-specific positive selection in both turkey and human astroviruses.
Protein Evolution From Sequence To Structure.
(2003-09-01) Buck, Michael Joseph; Jeff Thorne, Committee Member; Barbara Sherry, Committee Member; Michael Purugganan, Committee Member; William R. Atchley, Committee Chair
The purpose of this research is to elucidate how natural selection shapes protein evolution. The question was addressed by exploring protein sequence evolution, 3D structural evolution, and analysis of the multidimensional nature of amino acid covariation. This thesis begins with a study of protein sequence evolution. 118 different bHLH genes in the completely sequenced Arabidopsis thaliana genome and 131 bHLH genes in the rice genome were identified and characterized using phylogenetic analysis. These plant proteins were classified into 15 distinct plant clades and were under weaker selective constraints than their animal counterparts. Additionally, it was shown that lineage specific expansions and subfunctionalization have fashioned regulatory proteins for plant specific functions. To further characterize the bHLH domain, a canonical 3D structure was created from solved structures. This canonical structure was used as a template for producing 3D models for other representative bHLH proteins, which were then compared, contrasted, and grouped based on structural characteristics. Structural similarities were discovered within the bHLH domain between three clades (Max, Myc, and PbHLH-LZ). In addition, structural models of the Sat proteins suggest a strong similarity to other bHLH proteins, which is in disagreement with previous functional characterization. To further understand the dimensionality of protein evolution, the independence of amino acid sites was explored using multivariate factor analysis. A matrix of pairwise normalized mutual information values were computed among amino acid sites for the serpin proteins. The normalized mutual information matrix was partitioned into orthogonal dimensions by factor analysis. Each eigenvector from the factor analysis can be interpreted as having phylogenetic or structural/functional explanations or combinations of both. This approach discerns strong amino acid covariation within several key functional regions including the RCL, shutter, and breach. In addition, this approach elucidates hydrogen bonding, hydrophobic, and electrostatic interactions within the serpin protein family.