Biology subjects

Hill, J.

Publications and source records attributed to Hill, J..

6 recordsLinked to original sources

bioRxiv2018

A female alternative life-history strategy arose via novel recruitment of homeobox gene, BarH-1

Tradeoffs affect resource allocation during development and result in fitness consequences that drive the evolution of life history strategies. Yet despite their importance, we know little about the mechanisms underlying life history tradeoffs in wild populations. Many species of Colias butterflies exhibit an alternative life history strategy (ALHS) where females divert resources from wing pigment synthesis to reproductive and somatic development. Due to this reallocation, a wing color polymorphism is associated with the ALHS: individuals have either yellow/orange or white wings. Here we map the genetic basis of the ALHS switch in Colias crocea to a transposable element insertion downstream of the Colias homolog of BarH-1, a homeobox transcription factor. Using CRISPR/Cas9 gene editing, antibody staining, and electron microscopy we find morph-specific specific expression of BarH-1 suppresses the formation of pigment granules in wing scales. Lipid and transcriptome analyses reveal physiological differences associated with the ALHS. These findings characterize a novel mechanism for a female-limited ALHS and show that the switch arises via recruitment of a transcription factor previously known for its function in cell fate determination in pigment cells of the retina.

genomics↗

bioRxiv2018

Global cooling & the rise of modern grasslands: Revealing cause & effect of environmental change on insect diversification dynamics

Utilising geo-historical environmental data to disentangle cause and effect in complex natural systems is a major goal in our quest to better understand how climate change has shaped life on Earth. Global temperature is known to drive biotic change over macro-evolutionary time-scales but the mechanisms by which it acts are often unclear. Here, we model speciation rates for Orthoptera within a phylogenetic framework and use this to demonstrate that global cooling is strongly correlated with increased speciation rates. Transfer Entropy analyses reveal the presence of one or more additional processes that are required to explain the information transfer from global temperature to Orthoptera speciation. We identify the rise of C4 grasslands as one such mechanism operating from the Miocene onwards. We therefore demonstrate the value of the geological record in increasing our understanding of climate change on macro-evolutionary and macro-ecological processes.

ecology↗

bioRxiv2017

Maternal depression and child behaviours: sex-dependent mediation by glucocorticoid receptor gene methylation in a longitudinal study from pregnancy to age 5 years

BackgroundEvolutionary hypotheses predict that male fetuses are more vulnerable to poor maternal conditions than females (Sex-biased Maternal Investment), but that the adaptive female fetus, with a more responsive hypothalamic-pituitary-adrenal (HPA) axis, is put at later risk of glucocorticoid mediated disorders where there is a mismatch between fetal and postnatal environments (Predictive Adaptive Response). Self-report measures of prenatal and postnatal depression and maternal report of child anxious depressed symptoms at 2.5, 3.5 and 5.0 years were obtained from an extensive sample of first time mothers recruited from the general population (N = 794). Salivary NR3C1 1-F promoter methylation was assayed at 14 months in an intensive subsample (N = 176) stratified during pregnancy by psychosocial risk. Generalised structural equation models (SEM) were fitted and estimated by maximum likelihood to allow inclusion of participants from both intensive and extensive samples.\n\nResultsPostnatal depression was associated with NR3C1 methylation and with anxious-depressed symptoms in the daughters of mothers lacking the hypothesised protective effect of high prenatal depression (prenatal-postnatal depression interaction for methylation, p =.00001; for child symptoms, p = .011). In girls, NR3C1 methylation mediated the association between maternal depression and child anxious-depressed symptoms. The effects were greater in girls than boys, and the test of the sex differences in the effect of the prenatal-postnatal depression interaction on both outcomes gave {chi}2(2) = 5.95 (p=.051).\n\nConclusionsThis is the first study to show in humans that, as a result of sex-biased reproductive investment and fetal adaptation, epigenetic and early behavioural outcomes may arise through different mechanisms in males and females. Epigenetic effects at the NR3C1 promoter mediated mismatch between prenatal and postnatal maternal conditions and child anxious-depressed symptoms, specifically in females.

genetics↗

bioRxiv2017

Nkx2.5-dependent alterations of the embryonic heart DNA methylome identify novel cis-regulatory elements in cardiac development

Transcription factor Nkx2.5 is frequently mutated in congenital heart disease, but the mechanisms by which Nkx2.5 regulates heart development are poorly understood. By generating comprehensive DNA methylome maps from zebrafish embryonic hearts in nxk2.5 mutants and siblings, we discovered that Nkx2.5 regulates DNA methylation patterns during cardiac morphogenesis. We identified hundreds of Nkx-dependent heart-specific Differentially Methylated Regions (nhDMRs). A majority of the nhDMRs were hypomethylated in nkx2.5-/- hearts, correlating with changes in the mutant transcriptome, suggesting Nkx2.5 functions largely as a repressor. Distinct Nkx DNA-binding motifs were significantly enriched in subclasses of nhDMRs. Furthermore, nhDMRs were significantly associated with histone H3K4me1 and H3K27ac post-translational modifications, suggesting Nkx2.5 regulates gene expression by differential methylation of cis-regulatory elements. Using transgenics, we validated several nhDMRs with enhancer activities in the heart. We propose a novel role of Nkx2.5 mediated DNA methylation is integral in activating and repressing Nkx2.5 target genes during heart development.

developmental biology↗

bioRxiv2017

Genomic and proteomic analysis of Human herpesvirus 6 reveals distinct clustering of acute versus inherited forms and reannotation of reference strain

Human herpesvirus-6A and -6B (HHV-6) are betaherpesviruses that reach >90% seroprevalence in the adult population. Unique among human herpesviruses, HHV-6 can integrate into the subtelomeric regions of human chromosomes; when this occurs in germ line cells it causes a condition called inherited chromosomally integrated HHV-6 (iciHHV-6). To date, only two complete genomes are available for HHV-6B. Using a custom capture panel for HHV-6B, we report near-complete genomes from 61 isolates of HHV-6B from active infections (20 from Japan, 35 from New York state, and 6 from Uganda), and 64 strains of iciHHV-6B (mostly from North America). We also report partial genome sequences from 10 strains of iciHHV-6A. Although the overall sequence diversity of HHV-6 is limited relative to other human herpesviruses, our sequencing identified geographical clustering of HHV-6B sequences from active infections, as well as evidence of recombination among HHV-6B strains. One strain of active HHV-6B was more divergent than any other HHV-6B previously sequenced. In contrast to the active infections, sequences from iciHHV-6 cases showed reduced sequence diversity. Strikingly, multiple iciHHV-6B sequences from unrelated individuals were found to be completely identical, consistent with a founder effect. However, several iciHHV-6B strains intermingled with strains from active pediatric infection, consistent with the hypothesis that intermittent de novo integration into host germline cells can occur during active infection Comparative genomic analysis of the newly sequenced strains revealed numerous instances where conflicting annotations between the two existing reference genomes could be resolved. Combining these findings with transcriptome sequencing and shotgun proteomics, we reannotated the HHV-6B genome and found multiple instances of novel splicing and genes that hitherto had gone unannotated. The results presented here constitute a significant genomic resource for future studies on the detection, diversity, and control of HHV-6.\n\nAuthor SummaryHHV-6 is a ubiquitous large DNA virus that is the most common cause of febrile seizures and reactivates in allogeneic stem cell patients. It also has the unique ability among human herpesviruses to be integrated into the genome of every cell via integration in the germ line, a condition called inherited chromosomally integrated (ici)HHV-6, which affects approximately 1% of the population. To date, very little is known about the comparative genomics of HHV-6. We sequenced 61 isolates of HHV-6B from active infections, 64 strains of iciHHV-6B, and 10 strains of iciHHV-6A. We found geographic clustering of HHV-6B strains from active infections. In contrast, iciHHV-6B had reduced sequence diversity, with many identical sequences of iciHHV-6 found in individuals not known to share recent common ancestry, consistent with a founder effect from a remote common ancestor with iciHHV-6. We also combined our genomic analysis with transcriptome sequencing and shotgun proteomics to correct previous misannotations of the HHV-6 genome.

microbiology↗

bioRxiv2017

The Molecular Genetic Basis of Herbivory between Butterflies and their Host-Plants

Interactions between herbivorous insects and their host-plants are a central component of terrestrial food webs and a critical topic in agriculture, where a substantial fraction of potential crop yield is lost annually to pests. Important insights into plant-insect interactions have come from research on specific plant defenses and insect detoxification mechanisms. Yet, much remains unknown about the molecular mechanisms that mediate plant-insect interactions. Here we use multiple genome-wide approaches to map the molecular basis of herbivory from both plant and insect perspectives, focusing on butterflies and their larval host-plants. Parallel genome-wide association studies in the Cabbage White butterfly, Pieris rapae, and its host-plant, Arabidopsis thaliana, pinpointed a small number of butterfly and plant genes that influenced herbivory. These genes, along with much of the genome, were regulated in a dynamic way over the time course of the feeding interaction. Comparative analyses, including diverse butterfly/plant systems, showed a variety of genome-wide responses to herbivory, yet a core set of highly conserved genes in butterflies as well as their host-plants. These results greatly expand our understanding of the genomic causes and evolutionary consequences of ecological interactions across two of Natures most diverse taxa, butterflies and flowering plants.

genomics↗