Biology subjects

Morrill, K.

Publications and source records attributed to Morrill, K..

4 recordsLinked to original sources

bioRxiv2026

Evolutionary history and genomic vulnerability of the extinct giant deer Megaloceros giganteus

The extinct giant deer (Megaloceros giganteus) was one of the most striking megafaunal species of the Late Quaternary, distinguished by its enormous palmated antlers reaching up to 3.5 m across, the largest known among both living and extinct cervids. Despite its iconic status, little is known about its genomic history prior to extinction [~]8 thousand years ago (kya). We generated the first nuclear palaeogenomes for Megaloceros, represented by nine individuals from Germany ([~]40 kya) and Ireland ([~]11 kya), mapped to a new chromosome-level reference genome of the fallow deer (Dama dama). Phylogenomic analyses placed Megaloceros as sister to Dama (divergence [~]3.5 Ma) and revealed evidence of gene flow with ancestral Cervus lineages. Population analyses identified clear differentiation between German and Irish lineages, with higher genetic diversity in the German individuals. Two genes under strong positive selection, BNIPL and SLC10A7, are associated with apoptosis regulation and skeletal development/bone mineralisation, respectively, and may relate to the species large body and antler size. Demographic reconstructions indicate a long-term decline in effective population size, extremely low heterozygosity, little evidence of extensive runs of homozygosity, and an elevated burden of predicted deleterious alleles. Together, these results suggest that Megaloceros entered the terminal Pleistocene in a genomically fragile state, offering new insight into the biology and evolutionary legacy of one of the largest and most distinctive cervids that ever lived.

evolutionary biology↗

bioRxiv2023

A chromosome-level genome for the nudibranch gastropod Berghia stephanieae helps parse clade-specific gene expression in novel and conserved phenotypes

How novel phenotypes originate from conserved genes, processes, and tissues remains a major question in biology. Research that sets out to answer this question often focuses on the conserved genes and processes involved, an approach that explicitly excludes the impact of genetic elements that may be classified as clade-specific, even though many of these genes are known to be important for many novel, or clade-restricted, phenotypes. This is especially true for understudied phyla such as mollusks, where limited genomic and functional biology resources for members of this phylum has long hindered assessments of genetic homology and function. To address this gap, we constructed a chromosome-level genome for the gastropod Berghia stephanieae (Valdes, 2005) to investigate the expression of clade-specific genes across both novel and conserved tissue types in this species. The final assembled and filtered Berghia genome is comparable to other high quality mollusk genomes in terms of size (1.05 Gb) and number of predicted genes (24,960 genes), and is highly contiguous. The proportion of upregulated, clade-specific genes varied across tissues, but with no clear trend between the proportion of clade-specific genes and the novelty of the tissue. However, more complex tissue like the brain had the highest total number of upregulated, clade-specific genes, though the ratio of upregulated clade-specific genes to the total number of upregulated genes was low. Our results, when combined with previous research on the impact of novel genes on phenotypic evolution, highlight the fact that the complexity of the novel tissue or behavior, the type of novelty, and the developmental timing of evolutionary modifications will all influence how novel and conserved genes interact to generate diversity.

genomics↗

bioRxiv2023

tfboot: Bootstrapping and statistical analysis for transcription factor binding site-disrupting variants in gene sets

MotivationGenetic variants in noncoding regions can drive changes in phenotype disrupting transcription factor binding site (TFBS) motifs. Other tools including motifbreakR have been developed to assess the impact of TFBS-disrupting variants. Here we introduce the tfboot package for statistically evaluating the TFBS disruption across a set of variants in upstream promoter regions. ResultsThe tfboot package builds on motifbreakR, plyranges, and GenomicRanges to provide methods for bootstrapping TFBS disruption to statistically quantify the impact across gene sets of interest compared to an empirical null distribution. We demonstrate the analysis here on variants in the elephant genome. The tfboot package readily integrates with Bioconductor and tidyverse-based workflows. AvailabilityThe tfboot package is implemented as an R package and is released under the MIT license at https://github.com/colossal-compsci/tfboot.

bioinformatics↗

bioRxiv2016

Retrotransposon Activation Contributes to Neurodegeneration in a DrosophilaTDP-43 Model of ALS.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in [~]40% of FTLD cases, but the cascade of events leading to cell death are not understood. We have expressed human TDP-43 (hTDP-43) in Drosophila neurons and glia, a model that recapitulates many of the characteristics of TDP-43-linked human disease including protein aggregation pathology, locomotor impairment, and premature death. We report that such expression of hTDP-43 impairs small interfering RNA (siRNA) silencing, which is the major post-transcriptional mechanism of retrotransposable element (RTE) control in somatic tissue. This is accompanied by de-repression of a panel of both LINE and LTR families of RTEs, with somewhat different elements being active in response to hTDP-43 expression in glia versus neurons. hTDP-43 expression in glia causes an early and severe loss of control of a specific RTE, the endogenous retrovirus (ERV) gypsy. We demonstrate that gypsy causes the degenerative phenotypes in these flies because we are able to rescue the toxicity of glial hTDP-43 either by genetically blocking expression of this RTE or by pharmacologically inhibiting RTE reverse transcriptase activity. Moreover, we provide evidence that activation of DNA damage-mediated programmed cell death underlies both neuronal and glial hTDP-43 toxicity, consistent with RTE-mediated effects in both cell types. Our findings suggest a novel mechanism in which RTE activity contributes to neurodegeneration in TDP-43-mediated diseases such as ALS and FTLD.\n\nAUTHOR SUMMARYFunctional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in [~]40% of FTLD cases, and mutations in TDP-43 are causal in a subset of familial ALS cases. Although cytoplasmic inclusions of this mostly nuclear protein are a hallmark of the disease, the cascade of events leading to cell death are not understood. We demonstrate that expression of human TDP-43 (hTDP-43) in Drosophila neurons or glial cells, which results in toxic cytoplasmic accumulation of TDP-43, causes broad expression of retrotransposons. In the case of glial hTDP-43 expression, the endogenous retrovirus (ERV) gypsy causally contributes to degeneration because inhibiting gypsy genetically or pharmacologically is sufficient to rescue the phenotypic effects. Moreover, we demonstrate that activation of DNA damage-mediated programmed cell death underlies hTDP-43 and gypsy mediated toxicity. Finally, we find that hTDP-43 pathology impairs small interfering RNA silencing, which is an essential system that normally protects the genome from RTEs. These findings suggest a novel mechanism in which a storm of retrotransposon activation drives neurodegeneration in TDP-43 mediated diseases such as ALS and FTLD.

neuroscience↗