When Does Gene Flow Stop? A Mechanistic Approach to the Formation of Phylogeographic Breaks in Nature

I present a dissertation that examines the stochastic and deterministic predictors of population genetic demes between populations of organisms in nature. Gene flow patterns can increase the demographic viability of a population by increasing genetic diversity, and therefore reducing inbreeding depression and improving the population’s ability to adapt to changes in their biotic or abiotic environment. Conversely, gene flow patterns can negatively impact demographic health by flooding locally adapted phenotypes and reducing the population’s overall fitness, causing outbreeding depression. On the species level, disruptions in gene flow allow species to accumulate a variety of adaptations, and therefore provides the underlying variation necessary for the first step in diversification. In my dissertation, I use a variety of empirical and theoretical approaches to examine the mechanisms behind reductions in gene flow between natural populations. I propose that there are three common contributors to a breakdown in gene flow between populations: 1) the existence of an abiotic barrier that reduces migration by imposing intractable physiological costs on organisms that try to cross it, 2) ecological or behavioral properties of a population that reduce dispersal, such as reluctance to cross open areas that the species is still physically able to move through or 3) failure of dispersing individuals to survive in a new environment long enough to breed, possibly due to interspecific interactions, including predation and parasitism. The mechanisms behind these barriers are not mutually exclusive. Further, signatures of low gene flow between natural populations can reflect both deterministic barriers and stochastic patterns of movement of alleles across a landscape. Untangling all of this complexity requires a variety of theoretical and empirical approaches. I present empirical methods to identify geographic barriers that reduce gene flow between populations, and to identify cases in which genetic deme boundaries are not related to abiotic or biotic barriers but instead reflect stochastic patterns of migration. For this work I use night lizards from the genus Xantusia, including Xantusia vigilis and Xantusia riversiana. I use the discordance between SNP data derived from a ddRAD sequencing and microsatellite markers to better understand the demographic circumstances that result in the maintenance of phylogeographic breaks in the absence of a clear barrier to dispersal. I use an individual-based stochastic simulation inspired by natural polymorphic systems including Sonora snakes, Oophaga dart frogs, and Heliconius butterflies to identify mechanisms behind reduction gene flow due to predation. I propose a pipeline to use existing next-generation sequence data to integrate parasite biogeographic patterns into examinations of the mechanisms behind host population genetic patterns. My work on the complex and contingent nature of barriers to gene flow suggests that a hypothesis-testing framework, in which a suite of potential mechanisms are sequentially ruled out by the available evidence, might be the most productive approach to understanding patterns of genetic diversity in nature. Such an approach would be useful in conservation genetics, particularly in planning to maintain corridors for dispersal. Further, I suggest that improved understanding of the physiological tolerance of species of interest, and improved understanding of their biological context, can improve our predictions about the types of scenarios that lead to reductions in gene flow and ultimately set populations on the path to diversification.PHDEcology and Evolutionary BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155240/1/iholmes_1.pd

Authority Tools for Audiovisual and Music Catalogers: An Annotated List of Useful Resources

The Subcommittee on Authority Tools designed this list to bring together, in one place, descriptions of information sources that are useful when developing authorized headings to support audiovisual and music catalog records. Work began on this project in 1999, and the list was released in 2001. It became a historical OLAC document in 2020. Please note that links in this document were active in 2001 and may no longer exist currently

Adaptive Evolution of Staphylococcus aureus during Chronic Endobronchial Infection of a Cystic Fibrosis Patient

The molecular adaptation of Staphylococcus aureus to its host during chronic infection is not well understood. Comparative genome sequencing of 3 S. aureus isolates obtained sequentially over 26 months from the airways of a cystic fibrosis patient, revealed variation in phage content, and genetic polymorphisms in genes which influence antibiotic resistance, and global regulation of virulence. The majority of polymorphisms were isolate-specific suggesting the existence of an heterogeneous infecting population that evolved from a single infecting strain of S. aureus. The genetic variation identified correlated with differences in growth rate, hemolytic activity, and antibiotic sensitivity, implying a profound effect on the ecology of S. aureus. In particular, a high frequency of mutations in loci associated with the alternate transcription factor SigB, were observed. The identification of genes under diversifying selection during long-term infection may inform the design of novel therapeutics for the control of refractory chronic infections

A collection and analysis of amphibians and reptiles from Nicaragua with new country and departmental records

Nicaragua is a biodiverse country, but documented herpetological specimens are underrepresented compared to neighboring countries. In 2018 we conducted a collaborative expedition between the University of Michigan Museum of Zoology and Nicaraguan biologists. We visited sites in the Pacific Low‑ lands, Caribbean Lowlands, and the Central Highlands, representing the three major biogeographic regions of Nicaragua. We collected specimens of 100 species from a total of 106 encountered. We provide acces‑ sion numbers and morphological, genetic, and ecological information for these specimens. We recorded 23 new departmental records and the first country record of Metlapilcoatlus indomitus (Smith & Ferrari‑Castro, 2008), filling gaps in the known distribution of the species within Nicaragua and across Central America. When available for each species, we provide range maps and comparative genetic trees including conspecific reference sequences from the region, making this work a significant addition to existing checklists of the herpetofauna in Nicaragua

A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants

Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious.To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12-35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group ("C"). None of these new strains could be cultured in traditional cell lines.By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group

Genome-enabled insights into the biology of thrips as crop pests

Background The western flower thrips, Frankliniella occidentalis (Pergande), is a globally invasive pest and plant virus vector on a wide array of food, fiber, and ornamental crops. The underlying genetic mechanisms of the processes governing thrips pest and vector biology, feeding behaviors, ecology, and insecticide resistance are largely unknown. To address this gap, we present the F. occidentalis draft genome assembly and official gene set. Results We report on the first genome sequence for any member of the insect order Thysanoptera. Benchmarking Universal Single-Copy Ortholog (BUSCO) assessments of the genome assembly (size = 415.8 Mb, scaffold N50 = 948.9 kb) revealed a relatively complete and well-annotated assembly in comparison to other insect genomes. The genome is unusually GC-rich (50%) compared to other insect genomes to date. The official gene set (OGS v1.0) contains 16,859 genes, of which ~ 10% were manually verified and corrected by our consortium. We focused on manual annotation, phylogenetic, and expression evidence analyses for gene sets centered on primary themes in the life histories and activities of plant-colonizing insects. Highlights include the following: (1) divergent clades and large expansions in genes associated with environmental sensing (chemosensory receptors) and detoxification (CYP4, CYP6, and CCE enzymes) of substances encountered in agricultural environments; (2) a comprehensive set of salivary gland genes supported by enriched expression; (3) apparent absence of members of the IMD innate immune defense pathway; and (4) developmental- and sex-specific expression analyses of genes associated with progression from larvae to adulthood through neometaboly, a distinct form of maturation differing from either incomplete or complete metamorphosis in the Insecta. Conclusions Analysis of the F. occidentalis genome offers insights into the polyphagous behavior of this insect pest that finds, colonizes, and survives on a widely diverse array of plants. The genomic resources presented here enable a more complete analysis of insect evolution and biology, providing a missing taxon for contemporary insect genomics-based analyses. Our study also offers a genomic benchmark for molecular and evolutionary investigations of other Thysanoptera species

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass

Background and Aims The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. Methods This is retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all of the following were achieved: reaching the papilla, cannulating the desired duct and providing endoscopic therapy as clinically indicated. Results A total of 579 patients (median age 51, 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (IQR 109-210) with median ERCP time 40 minutes (IQR 28-56). Median hospital stay was 2 days (IQR 1-3). Adverse events were 18% (laparoscopy-related 10%, ERCP-related 7%, both 1%) with the clear majority (92%) classified as mild/moderate whereas 8% were severe and 1 death occurred. Conclusion Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher due to the added laparoscopy-related events

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder