Biology subjects

Leonard, C. J.

Publications and source records attributed to Leonard, C. J..

5 recordsLinked to original sources

bioRxiv2025

Acquired tick resistance in Peromyscus leucopus alters Ixodes scapularis infection

Ticks are obligate hematophagous parasites and pathogen vectors responsible for morbidity and mortality worldwide. Ixodes scapularis is a vector for at least seven pathogens relevant to human and animal health including the Lyme disease microbe, Borrelia burgdorferi, and the causative agent of anaplasmosis, Anaplasma phagocytophilum. Tick-host interactions are a driving influence on the maintenance of tick-borne pathogens in a population. Here, we report that repeated I. scapularis larval infestations on the wild host species Peromyscus leucopus leads to immune-mediated rejection of the tick, a phenomenon termed acquired tick resistance (ATR). We found that over 50% fewer larvae reached repletion and had decreased blood meal weights compared to larvae fed on naive hosts. Additionally, mice exhibited increasingly severe inflammation at tick bite sites characterized by an influx of basophils, eosinophils, neutrophils, and T lymphocytes. Larvae fed on sensitized mice ingested higher quantities of host leukocytes when compared to ticks fed on naive hosts, which rarely ingested nucleated cells. When challenged with B. burgdorferi or A. phagocytophilum, larvae fed on sensitized mice ingested more bacteria. Altogether, we demonstrate that reservoir host species develop ATR against larval I. scapularis, which reduces tick feeding success and affects pathogen ingestion by larvae. These results indicate that ATR could impact Ixodes population dynamics, prevalence of infected ticks, and pathogen circulation in the wild.

immunology↗

bioRxiv2019

Endless Conflicts: Detecting Molecular Arms Races in Mammalian Genomes

Recurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race - a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades - primates, mice, deer mice, dogs, and bats - to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for [~]100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.

evolutionary biology↗

bioRxiv2018

Extensive recombination suppression and chromosome-wide differentiation of a segregation distorter in Drosophila

Segregation distorters violate Mendelian Inheritance by over-representing themselves in the progeny of carrier individuals and are commonly associated with chromosomal inversions. When distorting alleles are found on sex chromosomes, the progeny of carrier individuals will exhibit skewed sex ratios, as exemplified by the array of Sex-Ratio (SR) distorting chromosomes found in Drosophila. Because of the strong selective pressures such chromosomes are thought to inflict on genomes, segregation distorters and their associated inversions are expected to experience rapid turn-over. However, the SR X-chromosome of Drosophila pseudoobscura is found at high frequencies in natural populations, forms stable latitudinal clines, appears to be unsuppressed, and shows evidence of being quite long-lived. Despite being a historically significant and well-studied segregation distortion system, the mechanisms allowing for the long-term persistence of the D. pseudoobscura SR chromosome remain unclear. Here, we perform a comparative genomic analysis between SR and uninverted standard X-chromosomes in D. pseudoobscura to study its evolutionary history and dynamics. We find a substantial level of differentiation between the SR and standard chromosome and estimate that the associated inversions have likely existed for the entire lifetime of the species (> 2 million generations). Through direct recombination experiments and population genetic analyses, we infer that this high level of differentiation is maintained by a combination of suppressed recombination and epistatic selection. Finally, our data reveal a massive mutational target size for protein and expression level changes specific to SR generated by its three non-overlapping inversions. Together our results imply that the entire SR chromosome in D. pseudoobscura behaves as a single co-adapted gene complex and has been maintained through a combination of suppressed recombination and epistatic selection. This finding highlights the dramatic consequences segregation distorters can have in shaping chromosome-wide patterns of recombination, nucleotide variation, and gene expression.

evolutionary biology↗

bioRxiv2018

Recurrent losses and rapid evolution of the condensin II complex in insects

Condensins play a crucial role in the organization of genetic material by compacting and disentangling chromosomes. The condensin I and condensin II complexes are widely considered to have distinct functions based on studies in a few model organisms, although the specific functions of each complex are yet to be fully understood. The condensin II complex is critical for genome organization in Drosophila, and is a key anti-pairing factor that separates homologous chromosomes in somatic cells. Intriguingly, the Cap-G2 subunit of condensin II is absent in Drosophila melanogaster, and this loss may be related to the high levels of homologous chromosome pairing in somatic cells seen in flies. Here, we find that this Cap-G2 loss predates the origin of Dipterans, and other CapG2 losses have occurred independently in multiple insect lineages. Furthermore, the Cap-H2 and Cap-D3 subunits have also been repeatedly and independently lost in several insect orders, and some taxa lack condensin II-specific subunits entirely. We used Oligopaint DNA-FISH to quantify pairing levels in ten species across seven orders, representing several different configurations of the condensin II complex. We find that all non-Dipteran insects display near-uniform low pairing levels, suggesting that some key aspects of genome organization are robust to condensin II subunit losses. Finally, we observe consistent signatures of positive selection in condensin II subunits across flies and mammals. These findings suggest that these ancient complexes are far more evolutionarily labile than previously suspected, and are at the crossroads of several forms of genomic conflicts. Our results raise fundamental questions about the specific functions of the two condensin complexes and the interplay between them in taxa that have experienced subunit losses, and open the door to further investigations to elucidate the diversity of molecular mechanisms that underlie genome organization across various life forms.

evolutionary biology↗

bioRxiv2018

The Impact of Reward on Attention in Schizophrenia

Traditionally, attention was thought to be directed by either top-down goals or bottom-up salience. Recent studies have shown that the reward history of a stimulus feature also acts as a powerful attentional cue. This is particularly relevant in schizophrenia, which is characterized by motivational and attentional deficits. Here, we examine the impact of reward on selective attention.\n\nForty-eight people with schizophrenia (PSZ) and 34 non-psychiatric control subject (NCS) discriminated the location of a target dot appearing inside a left circle or right circle. The circles were different colors, one of which was associated with reward via pre-training. In the first 2 blocks, targets were equally likely to appear in the left or right circle. In the last 4 blocks, the target was 75% likely on one side, thus allowing us to separately examine how attention was impacted by reward (color) and probability (location).\n\nPSZ had slower overall reaction times (RTs) than NCS. Both groups showed robust effects of spatial probability and reward history, with faster RTs for the rewarded color and for the more probable location. These effects were similar in PSZ and NCS. Negative symptom severity correlated with overall RT slowing, but there were no correlations between symptoms and reward-associated biasing of attention.\n\nPSZ demonstrated RT slowing but normal reward history and spatial probability-driven RT facilitation. These results are conceptually similar to prior findings showing intact implicit reward effects on response bias, and suggest that implicit processing of reward and probability is intact in PSZ.

neuroscience↗