Biology subjects

Miller, S. M.

Publications and source records attributed to Miller, S. M..

8 recordsLinked to original sources

bioRxiv2026

Maternal senescence broadly reprograms gene expression in offspring

Offspring of older parents have reduced fitness in many species, but the mechanisms mediating this cross-generational dimension of ageing remain poorly understood. Senescence is associated with genome-wide epigenetic changes that alter transcription, raising the possibility that older parents transmit dysregulated gene expression patterns. Here we show that maternal senescence induces deleterious, transcriptome-wide reprogramming of gene expression in offspring. Gene ontology and pathway enrichment analyses reveal that broad changes in gene expression that characterise maternal senescence in the clonally reproducing arthropod Folsomia candida are also observed at a young age in the offspring of older mothers. These concordant fold-changes are apparent at the whole-transcriptome level, and encompass conserved sequalae of senescence, including reduced carbon and energy metabolism. However, senescent mothers and their offspring also exhibit some contrasting gene expression patterns, representing distinct transcriptomic signatures of senescence that are not reflected in its cross-generational effects. The broad reprogramming of gene expression in offspring of older mothers is associated with substantially reduced fitness. Our findings show that older females can transmit a senescence-like gene expression syndrome to their offspring, inducing deleterious phenotypes from a young age.

genomics↗

bioRxiv2026

Flexible Asexuality: Naturally occurring variation in mechanisms of parthenogenesis within lineages and individuals of a facultative parthenogen, Megacrania batesii

Parthenogenesis is relatively rare and often regarded as an evolutionary dead end. Despite this, certain parthenogenetic animal species have endured for millions of years, but it is unclear what enables the persistence of some parthenogenetic lineages. Transitions from sexual to parthenogenetic reproduction can occur through different evolutionary processes that give rise to diverse cytological reproductive mechanisms. These mechanisms are likely to influence genetic diversity, especially in the early stages after the transition to parthenogenesis and may thus affect lineage persistence. To understand such evolutionary transitions, we used experimental crosses to investigate the mechanism of parthenogenesis and the immediate genetic consequences of switching from sexual to parthenogenetic reproduction in the facultatively parthenogenetic phasmid Megacrania batesii. We obtained DNA sequence data from multiple lineages propagated over three generations via sex, parthenogenesis, or transitions between reproductive modes. We quantified heterozygosity and within-family genetic variation and compared the genetic patterns with predictions for known mechanisms of parthenogenesis. We found that a single generation of parthenogenesis typically resulted in (near-)complete loss of heterozygosity and an absence of within-family genetic variation, consistent with automixis with gamete duplication or terminal fusion and little/no recombination. However, we also found evidence of variation in the mechanism of parthenogenesis among lineages and even within the same individual, associated with drastic differences in the amount of heterozygosity and within-family genetic variation maintained across generations. Our findings show that considerable variation in parthenogenetic mechanisms can exist within populations and suggest that such variation could influence the persistence and evolution of parthenogenetic lineages.

evolutionary biology↗

bioRxiv2024

Too hot to handle? The impact of the 2023 marine heatwave on Florida Keys coral

The marine heatwave in the summer of 2023 was the most severe on record for Floridas Coral Reef, with unprecedented water temperatures and cumulative thermal stress precipitating near 100% coral bleaching levels. An existing SCTLD coral fate-tracking program assessed over 4200 coral colonies across five offshore and four inshore reef sites approximately every two months, allowing for analyses of bleaching-related mortality and diseases during and after the marine heatwave. Across the vast majority of assessed corals, including multiple sites and species, there was no partial or full mortality as a result of the 2023 bleaching event. The two sites that did experience substantial bleaching-related mortality were those experiencing the highest levels of cumulative thermal stress. However, the substantial acute mortality at one of them occurred at relatively low levels of cumulative stress, suggesting death was the result of exceeding thermal maxima. At the two sites with notable mortality, 43% and 24% of all monitored corals died, but mortality varied among species. Brain corals fared worse than boulder corals, with Pseudodiploria strigosa the most heavily impacted species. The health status of corals before the bleaching event had little impact on whether they experienced disease or bleaching-related mortality during the event. At three sites, we observed unusual lesions on Orbicella faveolata colonies shortly after color returned to the corals; the lesions were only observed for a few months but on some colonies led to substantial tissue loss. Though not part of the coral monitoring program, we also observed substantial losses and local extinctions of Acroporid corals at most sites, as well as probable local extinctions of octocorals at three of the four inshore reefs. Though most reef-building corals came through the 2023 event with no mortality, continually rising temperatures are likely to make these temperature regimes more common and widespread. We encourage future research on what the unusual O. faveolata lesions are, and why the brain and boulder corals fared differently at highly-impacted sites. Our results also provide perspective on how restoration strategies, particularly those focused on species likely to die under current and future climate regimes, should consider shifting focus to species likely to survive. Finally, these results highlight the importance of this type of monitoring, with a focus on fate-tracking individuals through disturbance events, including a large number of individuals of multiple species across a geographic range and multiple habitats.

ecology↗

bioRxiv2024

Does ecology shape geographical parthenogenesis? Evidence from the facultatively parthenogenetic stick insect Megacrania batesii

Closely related sexual and parthenogenetic species often show distinct distribution patterns, known as geographical parthenogenesis. These patterns, characterized by a mosaic of separate sexual and parthenogenetic populations across their natural range, can also be found in facultative parthenogens - species in which every female is capable of both sexual and parthenogenetic reproduction. The underlying mechanisms driving this phenomenon in nature remain unclear. Features of the habitat, such as differences in host plant phenotypes or niche breadth, could favour sexual or asexual reproductive modes and thus help to explain geographical parthenogenesis in natural insect populations. Megacrania batesii is a facultatively parthenogenetic stick insect that displays geographical parthenogenesis in the wild. We aimed to explore whether sexual and parthenogenetic populations of M. batesii displayed niche differentiation or variations in niche breadth that could explain the separation of the two population types. To do this, we sampled host plants from across the range of M. batesii and quantified phenotypic traits that might affect palatability or accessibility for M. batesii, including leaf thickness, toughness, spike size and density, height, and chemical composition. We also quantified host plant density, which could affect M. batesii dispersal. We found little evidence of phenotypic differences between host plants supporting sexual versus asexual M. batesii populations, and no difference in host-plant density or niche breadth between the two population types. Our results suggest that habitat parameters do not play a substantial role in shaping patterns of geographical parthenogenesis in wild populations of M. batesii. Instead, population sex ratio variation could result from interactions between the sexes or dispersal dynamics.

evolutionary biology↗

bioRxiv2023

Micrococcin cysteine-to-thiazole conversion through transient interactions between a scaffolding protein and two modification enzymes

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, we demonstrate complex formation between TclI, TclJ and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core. IMPORTANCEThiopeptides are a family of antimicrobial peptides characterized for having sulfur-containing heterocycles and for being highly post-translationally modified. Numerous thiopeptides have been identified; almost all of which inhibit protein synthesis in gram-positive bacteria. These intrinsic antimicrobial properties make thiopeptides promising candidates for the development of new antibiotics. The thiopeptide micrococcin is synthesized by the ribosome and undergoes several post-translational modifications (PTMs) to acquire its bioactivity. In this study, we identify key interactions within the enzymatic complex that carries out cysteine to thiazole conversion in the biosynthesis of micrococcin.

biochemistry↗

bioRxiv2022

Genetic and phenotypic consequences of local transitions between sexual and parthenogenetic reproduction in the wild

Transitions from sexual to asexual reproduction have occurred in numerous lineages across the tree of life, but it remains unclear why asexual populations rarely persist. In facultatively parthenogenetic animals, all-female populations can arise when males are absent or become extinct, and such populations can give rise to obligately asexual species. Facultative parthenogens could therefore shed light on the initial stages of transitions to asexuality, and the factors that determine the success or failure of asexual populations. Here, we describe a novel spatial mosaic of mixed-sex and all-female populations of the facultatively parthenogenetic Australian phasmid Megacrania batesii, and use this system to investigate the consequences of reproductive mode variation in the wild. Analysis of single nucleotide polymorphisms (SNPs) indicated multiple, independent transitions between reproductive modes. As expected, all-female populations had drastically reduced heterozygosity and genetic diversity relative to mixed-sex populations. However, we found few consistent differences in fitness-related traits between population types. All-female populations exhibited more frequent and severe (non-functional) wing deformities, but did not show higher rates of appendage loss. All-female populations also harbored more parasites, but only in certain habitats. Reproductive mode explained little variation in female body size, fecundity, or egg hatch-rate. Our results confirm that transitions to parthenogenetic reproduction can lead to dramatic reductions in genetic diversity and heterozygosity. However, our findings also suggest that asexual M. batesii populations consist of high-fitness genotypes that might be able to thrive for many generations, perhaps until they encounter a drastic environmental change to which they are unable to adapt.

evolutionary biology↗

bioRxiv2021

Human primed endothelial colony forming cells exert neuroprotective effects in the growth restricted newborn piglet

The fetal brain is particularly vulnerable to the detrimental effects of fetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure fetal mesenchymal stem cells and endothelial colony forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of these primed ECFCs (pECFC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using mesenchymal stromal cells alone. These results demonstrate pECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and act as a neuroprotectant. One Sentence SummaryStem cell treatment improves brain outcomes in the growth restricted newborn

neuroscience↗

bioRxiv2021

Neurovascular unit alterations in the growth restricted newborn are improved following ibuprofen treatment

Fetal brain development is particularly vulnerable to the effects of fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant. Adverse outcomes range from behavioural and learning disorders through to cerebral palsy. Unfortunately, no treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, a non-steroidal anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. We used a preclinical piglet model of growth restriction in which FGR occurs spontaneously. Newborn FGR (birthweight <10th centile) and normally grown piglets were collected on day of birth and oral ibuprofen was administered daily for 3 days (20mg/kg/day, day 1 and 10mg/kg/day days 2 and 3). FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident in the microvasculature where leakage was present, suggestive of structural deficits to the NVU. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen treatment also attenuated albumin and IgG leakage. There were no alterations to angiogenesis, or blood vessel proliferation in treated-FGR piglets. These findings suggest postnatal administration of ibuprofen on day of birth modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.

neuroscience↗