Thesis.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Conservation biologists require information on the distribution, ecology, behaviour and genetic diversity of endangered species in order to identify threatened populations, determine which mechanisms are driving populations closer to extinction, and design appropriate mitigating solutions. The hazel dormouse, Muscardinus avellanarius, is declining across much of its northern range. Dormice are detrimentally affected by habitat degradation, loss and fragmentation. Despite extensive studies and conservation work on hazel dormice, there remain many gaps in our understanding. This thesis aims to fill some of those gaps. Hazel dormice are elusive, and therefore difficult to monitor in the wild. I demonstrate the utility of novel monitoring techniques for the rapid determination of dormouse presence, and provide algorithms for the objective verification of species identity from small mammal footprints. I design and utilise genetic microsatellite markers to investigate molecular ecology in this species. In one of the first studies of hazel dormouse population genetics, I describe high levels of population differentiation and genetic isolation across the southwest UK range. I find a powerful signal of reduction in genetic diversity, and an increase in differentiation between core and peripheral populations. I consider rival hypotheses for the mechanisms driving this population genetic pattern, and place the results in the context of conservation strategies for UK dormice. Further, I use molecular data to investigate the prevalence of multiple paternity in wild dormouse populations. Results contradict a recent estimate of very high rates of polyandry, but remain high at 50%. I investigate the effect of food availability on the hibernation behaviour of dormice. My findings, which demonstrate dormice are variable and flexible in their response to winter diet, increases our understanding of the trade-offs dormice must make in order to survive winter periods. I hope that the research undertaken for this thesis will add to the understanding and conservation of an iconic British mammal, ultimately contributing to the persistence of this species.

Thesis (Ph. D.)--University of Chicago, Pritzker School of Medicine, Committee on Genetics, August 2001. / Includes bibliographical references. Also available on the Internet.

Thesis (D. Sc.)--University of Adelaide, 1987. / Title from container. Includes bibliographies and indexes.

Thesis (M.Sc. (Anatomy))--Mahidol University, 1978. / Supported by the Stiftung Volkswagenwerk, Hannover, F.R. of Germany.

Mémoire de maîtrise (M.Med.Exp.)--Université du Québec à Chicoutimi, 1998. / Document électronique également accessible en format PDF. CaQCU

The ancient continent of Sahul, encompassing Australia, New Guinea and Tasmania, contains some of the earliest archaeological evidence for humans outside of Africa, dating back to at least 50 thousand years ago (kya). New Guinea was also one of the sites were humans developed agriculture in the last 10 thousand years. Despite the importance of this part of the world to the history of humanity outside Africa, little is known about the population history of the people living here. In this thesis I present population-genetic studies using whole-genome sequencing and genotype array datasets from more than 500 indigenous individuals from Australia and New Guinea, as well as initial work on large-scale sequencing of other, worldwide, human populations in the Human Genome Diversity Project panel. Other than recent admixture after European colonization of Australia, and Southeast Asian ad- mixture in the lowlands of New Guinea in the last few millennia, the populations of Sahul appear to have been genetically independent from the rest of the world since their divergence ∼50 kya. There is no evidence for South Asian gene flow to Australia, as previously suggested, and the highlands of Papua New Guinea (PNG) have remained unaffected by non-New Guinean gene flow until the present day. Despite Sahul being a single connected landmass until ∼8 kya, different groups across Australia are nearly equally related to Papuans, and vice versa, and the two appear to have separated genetically already ∼30 kya. In PNG, all highlanders strikingly appear to form a clade relative to lowlanders, and population structure seems to have been reshaped, with major population size increases, on the same timescale as the spread of agriculture. However, present- day genetic differentiation between groups is much stronger in PNG than in other parts of the world that have also transitioned to agriculture, demonstrating that such a lifestyle change does not necessarily lead to genetic homogenization. The results presented here provide detailed insights into the population history of Sahul, and sug- gests that its history can serve as an independent source of evidence for understanding human evolutionary trajectories, including the relationships between genetics, lifestyle, languages and culture.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu). / The distribution of variants of fourteen genetic and fourteen cytogenetic markers is investigated in samples from two Bedouin tribes, the Ajman (n = 52) and the Suluba (n = 52) and from the general population of Kuwait (n = 89). Typical of the many tribal populations in the Arabian peninsula, both Ajman and Suluba are socially isolated from each other. There is little documentation on the ancestral descent of both tribes. However, oral tradition regards Ajman as a deep-rooted Arabian tribe, while the Suluba is thought by some to have originated from the followers of the Crusade camps. The validity of the history of ancestral descent of both tribes is substantiated by a comparison of the distribution of several genetic markers with those of other peninsular communities, and by genetic distance measures between them, the peninsula Arabs of the South-West, and a European population (Italians). Distance measures were calculated by two different methods. Both genetic and cytogenetic marker data obtained from the three Kuwaiti communities contribute significantly to the sparse genetic information on the peninsular populations, and illustrate the degree of genetic microheterogeniety between these communities which was brought about by some social factors that caused their isolation. Gene flow from the neighboring East African populations is evident from the allelic distribution of certain systems such as the Duffy and the Rhesus. Evidence is presented which supports the speculation regarding the prevalence of K of the Kell system and M and S of the MNSs system in the indigeneous peninsular populations. A new salivary amylase isozyrne, Amy K1, was detected in a subject of probable Asiatic Indian descent sampled in Kuwait. Q-band chromosomal heteromorphisms were scored in the three sampled Kuwaiti communities. There was no statistical significance in the differences in frequencies of these heteromorphisms between the three samples. Genetic distances between the Kuwaiti communities and others from the literature were calculated on the basis of Q-band heteromorphic loci. The distances demonstrate the pitfalls in using absolute frequencies of chromosomal variants scored by different research groups for comparative studies. Large Y chromosome was present at high frequencies in the three Kuwaiti communities and was highest among members of the Ajman tribe. This finding suggests that the prevalance of large Y may be a distinguishing cytogenetic feature of the indigenous peninsular populations. Small Y was present in the sample from the general population, but not detected in either sample from the tribal communities. The differences in frequencies of Y chromosome variants between the three sampled communities was found to be statistically significant. Investigation of the 9qh region with the G-11 technique has shown an absence of inversions, partial and complete, of this heteromorphic region in the sample from the general population of Kuwait.

In this thesis the effects of individual and multiple environmental stressors (physical and chemical) are examined in inbred and outbred zebrafish (Danio rerio, Hamilton), a model species used in ecotoxicology and environmental risk assessment (ERA). The central question addressed is, are inbred laboratory animals representative and protective of wild populations? That is, are inbred fish equally or more sensitive to chemicals and other stressors compared with more outbred (wild) fish? A combination of tools and approaches incorporating traditional (eco)toxicology and population genetics have been employed, together with more contemporary molecular genetics and population modelling, to compare and contrast a range of responses in inbred and outbred zebrafish exposed to the endocrine disrupting chemical clotrimazole and/or temperature elevation in the laboratory. The choice of test species was based on our broad understanding of its basic biology, extending from the molecular level to the population level, and its wide use as a model organism in (eco)toxicology. Selection of the test chemical clotrimazole and temperature was based on a shared mode of action, aromatase inhibition, and therefore their ability to block oestrogen production, impair reproduction, promote male development and skew population sex ratios in zebrafish. A cascade of responses were compared in inbred and outbred zebrafish, including changes in the levels of expression of genes for gonadal aromatase and other steroidogenic enzymes, circulating sex steroid hormones, gonadal sex differentiation and development (via gonadal histopathology) and reproductive fitness (female fecundity, paternity and viability of embryos). Amongst the most striking results were directional skews in sex ratio towards males in response to clotrimazole (Chapter 5) and elevated temperature exposure (Chapter 7). Inbred fish were generally more responsive compared to outbreds, which showed evidence of physiological and developmental compensation, resulting in lower male-sex skews and superior fitness in terms of male reproductive success (paternity and viability of embryos). The greater effects observed in inbred fish were attributed to inbreeding×environment interactions and the amplification of inbreeding depression. Although no empirical genetic evidence of this mechanism is presented (loss of heterozygosity at quantitative trait loci and concomitant loss of heterosis and/or the expression of recessive, deleterious alleles in homozygotes), supporting evidence was provided by increased phenotypic variance in some apical endpoints in inbred fish, including specific growth rate and fecundity. This increased variance also has the potential to counteract the higher levels of response observed in inbreds, because the power to detect statistically significant changes in responses is reduced. This trade-off was demonstrated for specific growth rate. Crucially, significant male-sex ratio skews (>80%) were induced at substantially lower clotrimazole exposure concentrations (1.7 µg l-1) in combination with elevated temperature (33°C), compared with exposure concentrations (43.7 µg l-1) generating similar sex ratio skews at the standard test temperature of 28°C. These temperatures represent current and predicted 2100 (elevated) mean temperatures in the zebrafish’s native India and Bangladesh. Although the lowest observed effect concentration was an order of magnitude above the predicted environmental concentration for clotrimazole, it is conceivable that combined environmental exposures to similarly acting chemicals (e.g. other azole compounds used in crop protection, veterinary and human medicine) could produce similar effects to those we observed. The consequent effects of sex ratios skews and reduced fitness (fecundity and embryo viability) on per capita population growth rate (r) and extinction probability were predicted in inbred versus outbred zebrafish populations using stochastic population viability analysis. The results showed that the observed male-skews >80% threaten small zebrafish populations with fewer than 100 breeding adults (<20 adult females). However, small reductions of 2-3% in embryo-juvenile (age 0+) survivorship (including simulated inbreeding depression) were more influential on r and extinction probability than large sex ratio skews and/or reduced female fecundity. The results presented in this thesis support the contention that chemical effects may be exacerbated by other environmental stressors, but also illustrate the importance of considering biological (genetic), as well as physical and chemical interactions in cumulative ERA. Greater sensitivity of inbred versus outbred organisms to the effects of environmental stressors on sexual differentiation and reproductive fitness offers a margin of safety to ERA and the protection of wildlife populations (excluding those that are severely inbred and critically endangered). This is because, as originally stated, laboratory organisms used in ERA are generally more inbred than their wild counterparts. Nevertheless, more attention should be paid to the origin, breeding history and genetics of laboratory strains. This will help to ensure consistency between studies and testing laboratories and provide more confidence in extrapolating the results to wild populations.