Causes and Consequences of Broad-Scale Changes in the Distribution of Migratory Caribou (Rangifer tarandus) of Southern Hudson Bay

Understanding the factors driving changes in species distributions is fundamental to conservation, but for wide-ranging species this is often complicated by the need for broad-scale observations across space and time. In the last three decades, the location of summer concentrations of migratory caribou (Rangifer tarandus) in southern Hudson Bay (SHB), Canada, has shifted south and east as much as 500 km. We used long-term data (1987 – 2011) to test two hypotheses that could explain the distribution shift: forage depletion and anthropogenic disturbance. Over time and space, we compared the body size of live-captured adult female caribou, dietary quality from fecal nitrogen in July, the location of VHF- and GPS-collared female caribou in July, distribution of all-terrain vehicle (ATV) tracks and caribou tracks in August, and the proximity of collared caribou to sections of the coast with higher ATV activity in spring and summer. The forage depletion hypothesis was supported by greater body size and dietary quality in caribou of the eastern portion of SHB than in western SHB animals in 2009 – 11. The anthropogenic disturbance hypothesis was supported by the negative correlation of the distributions of ATV tracks and caribou tracks on the coast in 2010 and the fact that caribou avoided areas with ATV activity by 10 – 14 km. In 1987, collared caribou were observed largely along the coast in western SHB in mid-July, while in 2009 – 11, they were inland in western SHB and along the coast in eastern SHB. While these locations demonstrate a substantial change in summer distri­bution over three decades, we were unable to differentiate between forage depletion and anthropogenic disturbance as a single causal factor of the distribution shift.La compréhension des facteurs qui influencent les changements caractérisant les distributions des espèces est fondamentale aux efforts de conservation, mais pour les espèces dont l’aire de distribution est étendue, ce principe est souvent compliqué par la nécessité de faire des observations à grande échelle, dans le temps et dans l’espace. Au cours des trois dernières décennies, l’emplacement des concentrations estivales du caribou migrateur (Rangifer tarandus) dans le sud de la baie d’Hudson (SBH), au Canada, s’est déplacé vers le sud et vers l’est dans une mesure de 500 km. Nous nous sommes appuyés sur des données de longue haleine (1987–2011) pour mettre à l’épreuve deux hypothèses susceptibles d’expliquer ce changement en matière de distribution, soit l’appauvrissement du fourrage et la perturbation anthropique. Au fil du temps et de l’espace, nous avons comparé la taille du corps des caribous femelles adultes capturées vivantes, la qualité de leur alimentation à partir de l’azote fécal en juillet, l’emplacement des femelles portant un collier de type VHF ou GPS en juillet, la répartition des traces de véhicules tout terrain (VTT) et des pistes de caribou en août de même que la proximité des caribous portant un collier aux tronçons de la côte où la présence de VTT est plus grande au printemps et à l’été. L’hypothèse de l’appauvrissement du fourrage a été étayée par la plus grande taille du corps et la qualité de l’alimentation du caribou de la zone est du SBH comparativement à celles du caribou de l’ouest du SBH entre 2009 et 2011. Pour sa part, l’hypothèse perturbation anthropique a été appuyée par la corrélation négative caractérisant la répartition des pistes de VTT et des traces de caribou sur la côte en 2010 et par le fait que les caribous sont restés à l’écart des zones fréquentées par les VTT dans une mesure de 10 à 14 km. En 1987, des caribous portant un collier ont été observés en grand nombre le long de la côte ouest du SBH à la mi-juillet, tandis que de 2009 à 2011, ils ont été repérés à l’intérieur des terres dans l’ouest du SBH et le long de la côte est du SBH. Bien que ces emplacements indiquent un important changement en matière de distribution estivale au cours de trois décennies, nous n’avons pas été en mesure de faire une distinction entre l’appauvrissement du fourrage et la perturbation anthropique en tant que facteur causal unique du changement de distribution

Recent changes in summer distribution and numbers of migratory caribou on the southern Hudson Bay coast

The status of migratory woodland caribou inhabiting the coastal region in southern Hudson Bay is dynamic. The Pen Islands Herd within that region was defined in the 1990s, but opportunistic observations between 1999 and 2007 suggested that its status had significantly changed since the late 1980s and early 1990s. We undertook systematic surveys from the Hayes River, MB, to the Lakitusaki River, ON, in 2008 and 2009 to determine current distribution and minimum numbers of woodland caribou on the southern Hudson Bay coast from the Hayes River, Manitoba, to the Lakitusaki River, Ontario. We documented a significant change in summer distribution during the historical peak aggregation period (7-15 July) compared to the 1990s. In 2008 and 2009, respectively, we tallied 3529 and 3304 animals; however, fewer than 180 caribou were observed each year in the Pen Islands Herd’s former summer range where over 10 798 caribou were observed during a systematic survey in 1994. Over 80% of caribou were in the Cape Henrietta Maria area of Ontario. Calf proportions in herds varied from 8% of animals in the west to 20% in the east. Our 2008 and 2009 systematic surveys were focused on the immediate coast, but one exploratory flight inland suggested that more caribou may be inland than had been observed in the 1980s-1990s. The causes of change in the numbers and distribution in the coastal Hudson Bay Lowlands and the association of current caribou with the formerly large Pen Islands Herd may be difficult to determine because of gaps in monitoring, but satellite telemetry, genetic sampling, remote sensing, habitat analysis, and aboriginal knowledge are all being used to pursue answers

The Evolutionary Analysis of Emerging Low Frequency HIV-1 CXCR4 Using Variants through Time—An Ultra-Deep Approach

Large-scale parallel pyrosequencing produces unprecedented quantities of sequence data. However, when generated from viral populations current mapping software is inadequate for dealing with the high levels of variation present, resulting in the potential for biased data loss. In order to apply the 454 Life Sciences' pyrosequencing system to the study of viral populations, we have developed software for the processing of highly variable sequence data. Here we demonstrate our software by analyzing two temporally sampled HIV-1 intra-patient datasets from a clinical study of maraviroc. This drug binds the CCR5 coreceptor, thus preventing HIV-1 infection of the cell. The objective is to determine viral tropism (CCR5 versus CXCR4 usage) and track the evolution of minority CXCR4-using variants that may limit the response to a maraviroc-containing treatment regimen. Five time points (two prior to treatment) were available from each patient. We first quantify the effects of divergence on initial read k-mer mapping and demonstrate the importance of utilizing population-specific template sequences in relation to the analysis of next-generation sequence data. Then, in conjunction with coreceptor prediction algorithms that infer HIV tropism, our software was used to quantify the viral population structure pre- and post-treatment. In both cases, low frequency CXCR4-using variants (2.5–15%) were detected prior to treatment. Following phylogenetic inference, these variants were observed to exist as distinct lineages that were maintained through time. Our analysis, thus confirms the role of pre-existing CXCR4-using virus in the emergence of maraviroc-insensitive HIV. The software will have utility for the study of intra-host viral diversity and evolution of other fast evolving viruses, and is available from http://www.bioinf.manchester.ac.uk/segminator/

Wheat Domestication Accelerated Evolution and Triggered Positive Selection in the β-Xylosidase Enzyme of Mycosphaerella graminicola

Plant cell wall degrading enzymes (PCWDEs) of plant pathogens are receiving increasing interest for their potential to trigger plant defense reactions. In an antagonistic co-evolutionary arms race between host and pathogen, PCWDEs could be under strong selection. Here, we tested the hypothesis that PCWDEs in the fungal wheat pathogen Mycosphaerella graminicola have been positively selected by analyzing ratios of non-synonymous and synonymous nucleotide changes in the genes encoding these enzymes. Analyses of five PCWDEs demonstrated that one (β-xylosidase) has been under strong positive selection and experienced an accelerated rate of evolution. In contrast, PCWDEs in the closest relatives of M. graminicola collected from wild grasses did not show evidence for selection or deviation from a molecular clock. Since the genealogical divergence of M. graminicola from these latter species coincided with the onset of agriculture, we hypothesize that the recent domestication of the host plant and/or agricultural practices triggered positive selection in β-xylosidase and that this enzyme played a key role in the emergence of a host-specialized pathogen

Highly Sensitive and Specific Detection of Rare Variants in Mixed Viral Populations from Massively Parallel Sequence Data

Viruses diversify over time within hosts, often undercutting the effectiveness of host defenses and therapeutic interventions. To design successful vaccines and therapeutics, it is critical to better understand viral diversification, including comprehensively characterizing the genetic variants in viral intra-host populations and modeling changes from transmission through the course of infection. Massively parallel sequencing technologies can overcome the cost constraints of older sequencing methods and obtain the high sequence coverage needed to detect rare genetic variants (<1%) within an infected host, and to assay variants without prior knowledge. Critical to interpreting deep sequence data sets is the ability to distinguish biological variants from process errors with high sensitivity and specificity. To address this challenge, we describe V-Phaser, an algorithm able to recognize rare biological variants in mixed populations. V-Phaser uses covariation (i.e. phasing) between observed variants to increase sensitivity and an expectation maximization algorithm that iteratively recalibrates base quality scores to increase specificity. Overall, V-Phaser achieved >97% sensitivity and >97% specificity on control read sets. On data derived from a patient after four years of HIV-1 infection, V-Phaser detected 2,015 variants across the ∼10 kb genome, including 603 rare variants (<1% frequency) detected only using phase information. V-Phaser identified variants at frequencies down to 0.2%, comparable to the detection threshold of allele-specific PCR, a method that requires prior knowledge of the variants. The high sensitivity and specificity of V-Phaser enables identifying and tracking changes in low frequency variants in mixed populations such as RNA viruses

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

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Evolution of Linked Avirulence Effectors in Leptosphaeria maculans Is Affected by Genomic Environment and Exposure to Resistance Genes in Host Plants

Brassica napus (canola) cultivars and isolates of the blackleg fungus, Leptosphaeria maculans interact in a ‘gene for gene’ manner whereby plant resistance (R) genes are complementary to pathogen avirulence (Avr) genes. Avirulence genes encode proteins that belong to a class of pathogen molecules known as effectors, which includes small secreted proteins that play a role in disease. In Australia in 2003 canola cultivars with the Rlm1 resistance gene suffered a breakdown of disease resistance, resulting in severe yield losses. This was associated with a large increase in the frequency of virulence alleles of the complementary avirulence gene, AvrLm1, in fungal populations. Surprisingly, the frequency of virulence alleles of AvrLm6 (complementary to Rlm6) also increased dramatically, even though the cultivars did not contain Rlm6. In the L. maculans genome, AvrLm1 and AvrLm6 are linked along with five other genes in a region interspersed with transposable elements that have been degenerated by Repeat-Induced Point (RIP) mutations. Analyses of 295 Australian isolates showed deletions, RIP mutations and/or non-RIP derived amino acid substitutions in the predicted proteins encoded by these seven genes. The degree of RIP mutations within single copy sequences in this region was proportional to their proximity to the degenerated transposable elements. The RIP alleles were monophyletic and were present only in isolates collected after resistance conferred by Rlm1 broke down, whereas deletion alleles belonged to several polyphyletic lineages and were present before and after the resistance breakdown. Thus, genomic environment and exposure to resistance genes in B. napus has affected the evolution of these linked avirulence genes in L. maculans

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals

The interplay between structure and agency in shaping the mental health consequences of job loss

Main themes that emerged from the qualitative exploration of the psychological distress of job loss included stress, changes to perceived control, loss of self-esteem, shame and loss of status, experiencing a grieving process, and financial strain. Drawing on two models of agency we identified the different ways workers employed their agency, and how their agency was enabled, but mainly constrained, when dealing with job loss consequences. Respondents’ accounts support the literature on the moderating effects of economic resources such as redundancy packages. The results suggest the need for policies to put more focus on social, emotional and financial investment to mediate the structural constraints of job loss. Our study also suggests that human agency must be understood within an individual’s whole of life circumstances, including structural and material constraints, and the personal or interior factors that shape these circumstances.The authors acknowledge support from the National Health and Medical Research Council Capacity Building Grant (324724). The research was supported by the SA Department of Health and the SA Department of Families and Communities through the Human Services Research and Innovation Program (HSRIP), and the Australian Research Council Linkage Program (LP0562288), with the Department of Health (DOH) serving as Industry Partner. Professor Fran Baum was supported by an ARC Federation Fellowship and Drs Newman and Ziersch by the SA Premier’s Science and Research Fund