The adaptive landscape heuristic can be used to answer the question "how predictable is evolution?" because its topology will impact the repeatability of evolution. In my Masters research I addressed this question in two ways: (1) I reviewed empirical adaptive landscape studies in the fields of directed protein evolution and microbial experimental evolution and (2) I performed a selection experiment to characterize adaptive landscape topology by measuring variance in fitness and metabolic phenotype within and among genetically distinct Pseudomonas fluorescens strains in two environments. Empirical studies have found that protein level landscapes are generally smooth, however, population level landscapes are rugged even in simple environments. Experimentally I found that the pattern of variance in fitness and metabolic phenotype was unique to the selection environment. The response to selection was highly repeatable at the level of fitness, but the underlying genetic routes taken were different for each environment and more variable in xylose than in glucose, suggesting a more rugged underlying landscape. More generally, my research suggests that making statements about the predictability of adaptive evolution at the population level may be challenging and wi11likely depend on the specifics of the environment in which selection occurs.

Experimental evolution was used to independently evolve 12 replicate populations of Drosophila melanogaster for 34+ generations in one of three treatment environments of varying PO2: hypoxia (5.0-10.1 kPa), normoxia (21.3 kPa), and hyperoxia (40.5 kPa). Several traits related to whole animal performance and metabolism were monitored during experimental evolution and several common garden assays were performed at various stages to directly compare evolved and acclimatory differences between treatments. Results clearly demonstrate the evolution of increased anoxia tolerance in hypoxia-evolved populations, suggesting adaptation to this environment. This was correlated with an increase in citrate synthase activity compared to normoxic (control) populations, suggesting an increase in mitochondrial density in these populations. In contrast, no direct evidence of increased performance of the hyperoxia-evolved populations was detected, although an evolutionary cost was observed as a substantial decline in anoxia tolerance. Changes in performance did not result in an increase in any of the fitness components measured, including productivity and longevity, suggesting that these assays failed to capture the components of fitness relevant to adaptation.

My study is directed towards understanding the pattern of evolution taking place among populations of Peromyscus inhabiting the islands of British Columbia. A standard morphological approach, as veil as karyotype and reproductive isolation analyses, have shown that a taxonomic revision of this faunal group is desirable. I have proposed such a revision. A discriminant analysis utilizing morphological measurements reveals the existence of two distinctive phenotypes within the islands surveyed. Breeding studies, involving 78 pairs of insular Peromyscus, indicate that reproductive isolation exists between the two morph groups. Furthermore, when given the choice the large and small morph groups prefer the company of their own type. Extensive phallic variation occurs among island populations but no suggestion of taxonomic relationships are discernible. Karyotype analysis reveals that there are two distinct karyotypic patterns. The karyotype correlates with the two morphotype classifications. The large morph has a high number of metacentric chromosomes and the small morph has a low number. The high metacentric number karyotype is identical to that possessed by the morphologically similar Peromyscus sitkehsis known to inhabit the islands to the north of the.study group. Karyotype variation within each of the tvo major divisions is minimal. I have proposed that the karyotypic differences between these two morphs is significant at the species level. The large morph should be considered as P. sitkensis and the small phenotype should remain as P. maniculatus. The degree and rapidity of evolution within these Peromyscus populations requires a broadening in the scope of some subspecific taxa. Change in subspecific nomenclature has been indicated. Additional studies of Peromyscus upon the adjacent mainland and Vancouver Island are required before meaningful relationships can be expressed between insular and mainland groups at the subspecific level. / Science, Faculty of / Zoology, Department of / Graduate

We introduce a symbolic computational approach to detecting all permutation and parity symmetries in any general evolution equation, and to generating associated invariant polynomials, from given monomials, under the action of these symmetries. Traditionally, discrete point symmetries of differential equations are systemically found by solving complicated nonlinear systems of partial differential equations; in the presence of Lie symmetries, the process can be simplified further. Here, we show how to find parity- and permutation-type discrete symmetries purely based on algebraic calculations. Furthermore, we show that such symmetries always form groups, thereby allowing for the generation of new group-invariant conserved quantities from known conserved quantities. This work also contains an implementation of the said results in Mathematica. In addition, it includes, as a motivation for this work, an investigation of the connection between variational symmetries, described by local Lie groups, and conserved quantities in Hamiltonian systems.

HIV evolves very quickly permitting it to escape the immune system of an infected individual, limiting the effectiveness of drug treatment and making vaccine design extremely difficult. For these reasons identifying whether there are constraints on HIV evolution is of primary importance. In this thesis, I examined the relationships between sequence diversity and a number of factors including protein structure, co-evolution and RNA secondary structures, all of which contribute to evolutionary constraints. Firstly, I demonstrate that while there is an increase in sequence diversity over time, this variation has a tendency to be limited to specific structural regions. Relating the sequence variability of individual amino acid residues with three- dimensional protein structure, I find a significant difference between evolutionary rates in regions buried in the core of the protein as compared with those exposed on the surface. This result indicates that missense mutation is affected by structural constraints. Secondly, by relating recombinant breakpoint positions with the potential numbers of losses in amino acid interactions within the structure, I propose that as well as missense mutation, recombination is also affected by structural constraints, due to the need to maintain intra-molecular interactions. Thirdly, I demonstrate a relationship between conservation of RNA secondary structure and limited sequence variation in protein level, indicating RNA secondary structures are additional evolutionary constraint. This link between sequence and protein and RNA structures not only demonstrates the limits of recent HIV-1 evolution but also highlights the origins of evolutionary constraint on viral change. Lastly, I examined whether evolutionary constraints and co- evolution patterns of HIV genomes are applied in novel mosaic vaccine strategy and suggest that polyvalent mosaic vaccine sequence may generate proteins with stable structures and co-evolving units. Detailed understanding of the constraints that restrict HIV’s possible evolution will inform analysis of drug and immune escape.

One very significant characteristic of Hempel's covering-law models of scientific explanation, that is, the deductive-nomological model and the inductive-statistical model, is the supposed symmetry between explanation and prediction. In brief, the symmetry thesis asserts that explanation and prediction have the same logical structure; in other words, if an explanation of an. event had been taken account of in time, then it could have served as a basis for predicting the event in question, and vice versa. The present thesis is a critical analysis of the validity of this purported symmetry between explanation and prediction. The substance of the thesis begins with a defence against some common misconceptions of the symmetry thesis, for example, the idea that the symmetry concerns statements but not arguments. Specifically, Grunbaum's interpretation of the symmetry thesis as pertaining to the logical inferability rather than the epistemological symmetry between explanation and prediction is examined. The first sub-thesis of the symmetry thesis, namely that "Every adequate explanation is a potential prediction," is then analyzed. Purported counterexamples such as evolutionary theory and the paresis case are critically examined and consequently dismissed. Since there are conflicting views regarding the nature of explanation and prediction in evolutionary theory, a case study of the theory is also presented. Next, the second sub-thesis of the symmetry thesis, namely that "Every adequate prediction is a potential explanation," is discussed. In particular, the barometer case is discharged as a counterexample to the second sub-thesis when the explanatory power of indicator laws is properly understood. Finally, Salmon's current causal-relevance model of explanation, which claims to be an alternative to Hempel's inductive-statistical model, is critically analyzed. A modified inductive-statistical model of explanation is also proposed. This modified model retains the nomological ingredient of Hempel's original inductive-statistical model, but it is immune to criticisms raised against the latter. In conclusion, I maintain that there is indeed a symmetry between explanation and prediction. But since deductive-nomological explanation and prediction are essentially different from inductive-statistical explanation and prediction, the form the symmetry takes between deductive-nomological explanation and prediction differs from the form it exhibits between inductive-statistical explanation and prediction. / Arts, Faculty of / Philosophy, Department of / Graduate

M.Sc. / The current dogma that dictates that Natural Selection is the driving force behind evolutionary change, is finally being challenged - what with the upsurgence of evidence provided by molecular and developmental biologists. This genetic and ontogenic evidence points towards a far more holistic approach (such as the involvement of the cell as a whole, the external environment as well as a flexible genome) to evolution, in contrast to the previously accepted DNA-centric Mendelian hypothesis. This new wave of thought, together with the re-discovery of 18th and 19th century evolutionary thought that complies with current findings, was the motivation to expose other biological mechanisms that are able to induce evolutionary change. New concepts were introduced (that contradict Neo- Darwinian thinking), with the intention of placing Natural Selection in its rightful position as an adaptive mechanism. Concepts introduced, were firstly, a chapter on how genes produce their effects, and, that by simply reinserting or duplicating existing genes, drastic (macro-evolutionary) change would result. Here the genome is portrayed as a static and dynamic system. The phenomenon of repetition or duplication of existing genes provides evidence of common ancestry, as well as reinforcing the idea of regularity in evolution. Abundant evidence in nature reveals trends of regularity or constraint. Anything is not possible in evolutionary development. The search for laws of form and the reasons for their constraining variables are discussed. The most interesting evolutionary events are those that have led to major changes in the anatomical organisation of animals. These changes are associated with the formation of new phyla. All that remains of such highly significant events are the time-locked tales of fossils. However, the fossil record cannot begin to reveal how these events occurred. The final chapter speculates on how life may have begun in the primordial waters and ends at a hypothesis on the origin of eukaryotes. The scription was an attempt to nudge the prevailing "Darwin" orientated evolutionary paradigm, in order to create space for the arrival of an "Epigenetic" orientated evolutionary paradigm, that is completely able to explain evolutionary procedure.

Aspects of the behavioral ecology of bird song learning are examined in three parts. First, an approach from image analysis is extended to allow rapid, quantitative description of animal sounds. In this approach, sounds are summarized as sets of time-frequency-amplitude landmarks. Second, the role of dawn song in tree swallow (Tachycineta bicolor) breeding biology is examined. Song syllable sharing among tree swallows was found to be high among birds nesting at the same site, but sharing was lower between birds nesting at different sites. When birds nested at different sites, the distance between those sites was not related to the amount of difference between the birds' syllable repertoire compositions. All tree swallow song repertoires did not remain constant during the breeding season; some individuals added new syllable types, others modified existing types. Singing performance was correlated with reproductive success in tree swallows: males that sang more precise repetitions of their syllable types attracted more extra-pair mates. Furthermore, pairwise comparisons between the social and genetic fathers of extra-pair young found that the genetic fathers averaged higher syllable consistency than the cuckolded males. Third, a comparative study of the phylogenetic distribution of vocal mimicry examined the evolutionary history of song learning in oscine passerines. Vocal mimicry, defined as the habitual incorporation of heterospecific sounds into song displays, was found in twenty-eight separate clades of oscines. These clades were found in every major oscine superfamily, but made up a higher proportion of daughter groups within the most ancient superfamilies of oscines. The most plesiomorphic lineages of oscines were found to contain many highly-skilled mimics. These observations support the hypothesis that the course of song learning in oscines has run repeatedly from permissive learning rules that permit mimicry to restrictive learning rules that limit mimicry.

Under the Dobzhansky-Muller model, postzygotic isolation results from incompatibility between interacting genes. Evidence points to regulatory networks as a rich source of incompatibilities that impact hybrid fitness. Pleiotropy is a natural feature of regulatory networks because regulatory elements generally have multiple targets. Both pleiotropy and hybrid incompatibility arise due to genetic interactions; therefore we can expect an intimate association between them. In the following chapters, I investigate the relationship between pleiotropy and hybrid incompatibility in the context of regulatory networks. In chapter one, I extend a general network-based study of hybrid incompatibility by incorporating a sequence-based thermodynamic model of transcriptional regulation. In the absence of pleiotropy, hybrid misregulation of a positively selected trait evolves quickly as a consequence of non-recognition or spurious binding in regulatory interactions across species boundaries. In a conserved trait, hybrid incompatibility evolves much slower as a product of compensatory drift. In chapter two, I show that pleiotropy can promote or constrain the evolution of hybrid incompatibility in a regulatory network depending on its fitness landscape, which emerges from the thermodynamic properties of molecular binding. Pleiotropy may promote hybrid incompatibility in accordance with the "selection, pleiotropy, and compensation model" of evolution, in which compensation for the pleiotropic side-effects of adaptation accelerates incompatibility in conserved traits. Pleiotropy can limit the evolution of hybrid incompatibility by constraining change in trans-acting regulatory elements in favor of adaptation at less pleiotropic downstream cis-regulatory targets. Without change in both interactors, incompatibility does not occur under the Dobzhansky-Muller model. In chapter three, I evaluate the hypothesis that pleiotropy facilitates the onset of hybrid incompatibility under antagonistic coevolution, an ubiquitous and persistent source of natural selection. When infectivity and resistance in a host-parasite system are determined epistatically by network interactions, reciprocal selective pressure results in a genotypic chase. This causes pleiotropic mutations to accumulate and be compensated over time, producing intrinsic hybrid incompatibility in both species independent of local adaptation. Thus, cyclical antagonistic coevolution eventually overcomes constraint on pleiotropic loci, facilitating the evolution of regulatory incompatibilities commonly observed in hybrids.

The carotenoid tradeoff hypothesis states that diet-derived carotenoids are traded-off among competing physiological demands, but this statement is rarely tested in ornamented females. The following dissertation tests the carotenoid tradeoff hypothesis in reverse sexually dimorphic convict cichlids (Amantitlania siquia) using carotenoid-supplemented diet treatments and a field-based study of carotenoid intake. Spectral, microscopic, and chemical analysis determined how females allocated the pigments to tissues and how those decisions affected their ventral patch coloration. The results presented in the current study show that carotenoids enhance offspring growth and survival, lower oxidative stress, and reduce the time to clear a parasite. The two final chapters suggest that carotenoid limitation and absorption may not explain carotenoid allocation dynamics in A. siquia. The final chapter proposes an alternative to the carotenoid tradeoff hypothesis as a mechanism to explain the relationship among color, parasites, and oxidative stress.