A diffusion approach to approximating preservation probabilities for gene duplicates

Consider a haploid population and, within its genome, a gene whose presence is vital for the survival of any individual. Each copy of this gene is subject to mutations which destroy its function. Suppose one member of the population somehow acquires a duplicate copy of the gene, where the duplicate is fully linked to the original gene's locus. Preservation is said to occur if eventually the entire population consists of individuals descended from this one which initially carried the duplicate. The system is modelled by a finite state-space Markov process which in turn is approximated by a diffusion process, whence an explicit expression for the probability of preservation is derived. The event of preservation can be compared to the fixation of a selectively neutral gene variant initially present in a single individual, the probability of which is the reciprocal of the population size. For very weak mutation, this and the probability of preservation are equal, while as mutation becomes stronger, the preservation probability tends to double this reciprocal. This is in excellent agreement with simulation studies.

Directional genetic differentiation and relative migration

Understanding the population structure and patterns of gene flow within species is of fundamental importance to the study of evolution. In the fields of population and evolutionary genetics, measures of genetic differentiation are commonly used to gather this information. One potential caveat is that these measures assume gene flow to be symmetric. However, asymmetric gene flow is common in nature, especially in systems driven by physical processes such as wind or water currents. As information about levels of asymmetric gene flow among populations is essential for the correct interpretation of the distribution of contemporary genetic diversity within species, this should not be overlooked. To obtain information on asymmetric migration patterns from genetic data, complex models based on maximum-likelihood or Bayesian approaches generally need to be employed, often at great computational cost. Here, a new simpler and more efficient approach for understanding gene flow patterns is presented. This approach allows the estimation of directional components of genetic divergence between pairs of populations at low computational effort, using any of the classical or modern measures of genetic differentiation. These directional measures of genetic differentiation can further be used to calculate directional relative migration and to detect asymmetries in gene flow patterns. This can be done in a user-friendly web application called divMigrate-online introduced in this study. Using simulated data sets with known gene flow regimes, we demonstrate that the method is capable of resolving complex migration patterns under a range of study designs.

Contemporary population genetic structure and phylogeography of pink salmon

Thesis (Master's)--University of Washington, 2016-06

CCEA A2 unit 2 Biology : biochemistry, genetics and evolutionary trends.

Guía de revisión para alumnos de educación secundaria de segundo ciclo que estén preparando el examen CCEA (Council for the Curriculum Examinations and Assessment) en el nivel A2 del área de biología. Está dividido en tres secciones: una introducción con orientación y consejos sobre el examen; una guía de contenidos con un resumen de las materias y conceptos básicos necesarios para superar la prueba organizados en ocho temas (respiración, fotosíntesis, ADN, tecnología genética, genes y patrones de herencia, genética de poblaciones, evolución y especiación, reino plantae y reino animal); y un apartado con dos ejemplos de exámenes y dos juegos de respuestas reales de alumnos comentadas por un examinador.

Population genetics of VNTR loci and their applications in evolutionary studies

Variable number of tandem repeats (VNTR) are genetic loci at which short sequence motifs are found repeated different numbers of times among chromosomes. To explore the potential utility of VNTR loci in evolutionary studies, I have conducted a series of studies to address the following questions: (1) What are the population genetic properties of these loci? (2) What are the mutational mechanisms of repeat number change at these loci? (3) Can DNA profiles be used to measure the relatedness between a pair of individuals? (4) Can DNA fingerprint be used to measure the relatedness between populations in evolutionary studies? (5) Can microsatellite and short tandem repeat (STR) loci which mutate stepwisely be used in evolutionary analyses?^ A large number of VNTR loci typed in many populations were studied by means of statistical methods developed recently. The results of this work indicate that there is no significant departure from Hardy-Weinberg expectation (HWE) at VNTR loci in most of the human populations examined, and the departure from HWE in some VNTR loci are not solely caused by the presence of population sub-structure.^ A statistical procedure is developed to investigate the mutational mechanisms of VNTR loci by studying the allele frequency distributions of these loci. Comparisons of frequency distribution data on several hundreds VNTR loci with the predictions of two mutation models demonstrated that there are differences among VNTR loci grouped by repeat unit sizes.^ By extending the ITO method, I derived the distribution of the number of shared bands between individuals with any kinship relationship. A maximum likelihood estimation procedure is proposed to estimate the relatedness between individuals from the observed number of shared bands between them.^ It was believed that classical measures of genetic distance are not applicable to analysis of DNA fingerprints which reveal many minisatellite loci simultaneously in the genome, because the information regarding underlying alleles and loci is not available. I proposed a new measure of genetic distance based on band sharing between individuals that is applicable to DNA fingerprint data.^ To address the concern that microsatellite and STR loci may not be useful for evolutionary studies because of the convergent nature of their mutation mechanisms, by a theoretical study as well as by computer simulation, I conclude that the possible bias caused by the convergent mutations can be corrected, and a novel measure of genetic distance that makes the correction is suggested. In summary, I conclude that hypervariable VNTR loci are useful in evolutionary studies of closely related populations or species, especially in the study of human evolution and the history of geographic dispersal of Homo sapiens. (Abstract shortened by UMI.) ^

Latent variable models in statistical genetics

Understanding the complexities that are involved in the genetics of multifactorial diseases is still a monumental task. In addition to environmental factors that can influence the risk of disease, there is also a number of other complicating factors. Genetic variants associated with age of disease onset may be different from those variants associated with overall risk of disease, and variants may be located in positions that are not consistent with the traditional protein coding genetic paradigm. Latent Variable Models are well suited for the analysis of genetic data. A latent variable is one that we do not directly observe, but which is believed to exist or is included for computational or analytic convenience in a model. This thesis presents a mixture of methodological developments utilising latent variables, and results from case studies in genetic epidemiology and comparative genomics. Epidemiological studies have identified a number of environmental risk factors for appendicitis, but the disease aetiology of this oft thought useless vestige remains largely a mystery. The effects of smoking on other gastrointestinal disorders are well documented, and in light of this, the thesis investigates the association between smoking and appendicitis through the use of latent variables. By utilising data from a large Australian twin study questionnaire as both cohort and case-control, evidence is found for the association between tobacco smoking and appendicitis. Twin and family studies have also found evidence for the role of heredity in the risk of appendicitis. Results from previous studies are extended here to estimate the heritability of age-at-onset and account for the eect of smoking. This thesis presents a novel approach for performing a genome-wide variance components linkage analysis on transformed residuals from a Cox regression. This method finds evidence for a dierent subset of genes responsible for variation in age at onset than those associated with overall risk of appendicitis. Motivated by increasing evidence of functional activity in regions of the genome once thought of as evolutionary graveyards, this thesis develops a generalisation to the Bayesian multiple changepoint model on aligned DNA sequences for more than two species. This sensitive technique is applied to evaluating the distributions of evolutionary rates, with the finding that they are much more complex than previously apparent. We show strong evidence for at least 9 well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least 7 classes in an alignment of four mammals, including human. A pattern of enrichment and depletion of genic regions in the profiled segments suggests they are functionally significant, and most likely consist of various functional classes. Furthermore, a method of incorporating alignment characteristics representative of function such as GC content and type of mutation into the segmentation model is developed within this thesis. Evidence of fine-structured segmental variation is presented.

Evolutionary biology of Gondwanan non-biting midges (Diptera: Chironomidae)

The potential restriction to effective dispersal and gene flow caused by habitat fragmentation can apply to multiple levels of evolutionary scale; from the fragmentation of ancient supercontinents driving diversification and speciation on disjunct landmasses, to the isolation of proximate populations as a result of their inability to cross intervening unsuitable habitat. Investigating the role of habitat fragmentation in driving diversity within and among taxa can thus include inferences of phylogenetic relationships among taxa, assessments of intraspecific phylogeographic structure and analyses of gene flow among neighbouring populations. The proposed Gondwanan clade within the chironomid (non-biting midge) subfamily Orthocladiinae (Diptera: Chironomidae) represents a model system for investigating the role that population fragmentation and isolation has played at different evolutionary scales. A pilot study by Krosch et al (2009) indentified several highly divergent lineages restricted to ancient rainforest refugia and limited gene flow among proximate sites within a refuge for one member of this clade, Echinocladius martini Cranston. This study provided a framework for investigating the evolutionary history of this taxon and its relatives more thoroughly. Populations of E. martini were sampled in the Paluma bioregion of northeast Queensland to investigate patterns of fine-scale within- and among-stream dispersal and gene flow within a refuge more rigorously. Data was incorporated from Krosch et al (2009) and additional sites were sampled up- and downstream of the original sites. Analyses of genetic structure revealed strong natal site fidelity and high genetic structure among geographically proximate streams. Little evidence was found for regular headwater exchange among upstream sites, but there was distinct evidence for rare adult flight among sites on separate stream reaches. Overall, however, the distribution of shared haplotypes implied that both larval and adult dispersal was largely limited to the natal stream channel. Patterns of regional phylogeographic structure were examined in two related austral orthoclad taxa – Naonella forsythi Boothroyd from New Zealand and Ferringtonia patagonica Sæther and Andersen from southern South America – to provide a comparison with patterns revealed in their close relative E. martini. Both taxa inhabit tectonically active areas of the southern hemisphere that have also experienced several glaciation events throughout the Plio-Pleistocene that are thought to have affected population structure dramatically in many taxa. Four highly divergent lineages estimated to have diverged since the late Miocene were revealed in each taxon, mirroring patterns in E. martini; however, there was no evidence for local geographical endemism, implying substantial range expansion post-diversification. The differences in pattern evident among the three related taxa were suggested to have been influenced by variation in the responses of closed forest habitat to climatic fluctuations during interglacial periods across the three landmasses. Phylogeographic structure in E. martini was resolved at a continental scale by expanding upon the sampling design of Krosch et al (2009) to encompass populations in southeast Queensland, New South Wales and Victoria. Patterns of phylogeographic structure were consistent with expectations and several previously unrecognised lineages were revealed from central- and southern Australia that were geographically endemic to closed forest refugia. Estimated divergence times were congruent with the timing of Plio-Pleistocene rainforest contractions across the east coast of Australia. This suggested that dispersal and gene flow of E. martini among isolated refugia was highly restricted and that this taxon was susceptible to the impacts of habitat change. Broader phylogenetic relationships among taxa considered to be members of this Gondwanan orthoclad group were resolved in order to test expected patterns of evolutionary affinities across the austral continents. The inferred phylogeny and estimated divergence times did not accord with expected patterns based on the geological sequence of break-up of the Gondwanan supercontinent and implied instead several transoceanic dispersal events post-vicariance. Difficulties in appropriate taxonomic sampling and accurate calibration of molecular phylogenies notwithstanding, the sampling regime implemented in the current study has been the most intensive yet performed for austral members of the Orthocladiinae and unsurprisingly has revealed both novel taxa and phylogenetic relationships within and among described genera. Several novel associations between life stages are made here for both described and previously unknown taxa. Investigating evolutionary relationships within and among members of this clade of proposed Gondwanan orthoclad taxa has demonstrated that a complex interaction between historical population fragmentation and dispersal at several levels of evolutionary scale has been important in driving diversification in this group. While interruptions to migration, colonisation and gene flow driven by population fragmentation have clearly contributed to the development and maintenance of much of the diversity present in this group, long-distance dispersal has also played a role in influencing diversification of continental biotas and facilitating gene flow among disjunct populations.

Multiple evolutionary rate classes in animal genome evolution

The proportion of functional sequence in the human genome is currently a subject of debate. The most widely accepted figure is that approximately 5% is under purifying selection. In Drosophila, estimates are an order of magnitude higher, though this corresponds to a similar quantity of sequence. These estimates depend on the difference between the distribution of genomewide evolutionary rates and that observed in a subset of sequences presumed to be neutrally evolving. Motivated by the widening gap between these estimates and experimental evidence of genome function, especially in mammals, we developed a sensitive technique for evaluating such distributions and found that they are much more complex than previously apparent. We found strong evidence for at least nine well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least seven classes in an alignment of four mammals, including human. We also identified at least three rate classes in human ancestral repeats. By positing that the largest of these ancestral repeat classes is neutrally evolving, we estimate that the proportion of nonneutrally evolving sequence is 30% of human ancestral repeats and 45% of the aligned portion of the genome. However, we also question whether any of the classes represent neutrally evolving sequences and argue that a plausible alternative is that they reflect variable structure-function constraints operating throughout the genomes of complex organisms.

Review ["Telling the Evolutionary Time : Molecular Clocks and the Fossil Record" edited by Philip C. J. Donoghue and M. Paul Smith]

Determining the temporal scale of biological evolution has traditionally been the preserve of paleontology, with the timing of species originations and major diversifications all being read from the fossil record. However, the ages of the earliest (correctly identified) records will underestimate actual origins due to the incomplete nature of the fossil record and the necessity for lineages to have evolved sufficiently divergent morphologies in order to be distinguished. The possibility of inferring divergence times more accurately has been promoted by the idea that the accumulation of genetic change between modern lineages can be used as a molecular clock (Zuckerkandl and Pauling, 1965). In practice, though, molecular dates have often been so old as to be incongruent even with liberal readings of the fossil record. Prominent examples include inferred diversifications of metazoan phyla hundreds of millions of years before their Cambrian fossil record appearances (e.g., Nei et al., 2001) and a basal split between modern birds (Neoaves) that is almost double the age of their earliest recognizable fossils (e.g., Cooper and Penny, 1997).

Accounting for calibration uncertainty in phylogenetic estimation of evolutionary divergence times

The estimation of phylogenetic divergence times from sequence data is an important component of many molecular evolutionary studies. There is now a general appreciation that the procedure of divergence dating is considerably more complex than that initially described in the 1960s by Zuckerkandl and Pauling (1962, 1965). In particular, there has been much critical attention toward the assumption of a global molecular clock, resulting in the development of increasingly sophisticated techniques for inferring divergence times from sequence data. In response to the documentation of widespread departures from clocklike behavior, a variety of local- and relaxed-clock methods have been proposed and implemented. Local-clock methods permit different molecular clocks in different parts of the phylogenetic tree, thereby retaining the advantages of the classical molecular clock while casting off the restrictive assumption of a single, global rate of substitution (Rambaut and Bromham 1998; Yoder and Yang 2000).

The evolutionary history of cockatoos (Aves: Psittaciformes: Cacatuidae)

Cockatoos are the distinctive family Cacatuidae, a major lineage of the order of parrots (Psittaciformes) and distributed throughout the Australasian region of the world. However, the evolutionary history of cockatoos is not well understood. We investigated the phylogeny of cockatoos based on three mitochondrial and three nuclear DNA genes obtained from 16 of 21 species of Cacatuidae. In addition, five novel mitochondrial genomes were used to estimate time of divergence and our estimates indicate Cacatuidae diverged from Psittacidae approximately 40.7 million years ago (95% CI 51.6–30.3 Ma) during the Eocene. Our data shows Cacatuidae began to diversify approximately 27.9 Ma (95% CI 38.1–18.3 Ma) during the Oligocene. The early to middle Miocene (20–10 Ma) was a significant period in the evolution of modern Australian environments and vegetation, in which a transformation from mainly mesic to xeric habitats (e.g., fire-adapted sclerophyll vegetation and grasslands) occurred. We hypothesize that this environmental transformation was a driving force behind the diversification of cockatoos. A detailed multi-locus molecular phylogeny enabled us to resolve the phylogenetic placements of the Palm Cockatoo (Probosciger aterrimus), Galah (Eolophus roseicapillus), Gang-gang Cockatoo (Callocephalon fimbriatum) and Cockatiel (Nymphicus hollandicus), which have historically been difficult to place within Cacatuidae. When the molecular evidence is analysed in concert with morphology, it is clear that many of the cockatoo species’ diagnostic phenotypic traits such as plumage colour, body size, wing shape and bill morphology have evolved in parallel or convergently across lineages.