Biology subjects

Shingleton, A.

Publications and source records attributed to Shingleton, A..

5 recordsLinked to original sources

bioRxiv2026

Hypoxia couples growth and developmental timing by decoupling steroid synthesis and secretion

In almost all animals, low physiological levels of oxygen (hypoxia) reduce growth rate and adult body size. Despite the near ubiquity of this response, the systemic mechanisms that coordinate growth and development under hypoxia remain poorly understood. In Drosophila, hypoxia increases circulating levels of the steroid hormone ecdysone to inhibit insulin/IGF signaling and slow growth. At the same time, ecdysone biosynthesis is reduced to delay pupation and extend development. Traditionally, the secretion of lipid-soluble steroids is thought to be regulated at the level of biosynthesis. This therefore presents a paradox: how can a single environmental factor both increase ecdysone levels yet decrease ecdysone synthesis? Our data show that this paradox is resolved by the dual regulation of ecdysone at the levels of secretion and biosynthesis. We show that, in the short term, hypoxia increases basal levels of ecdysone via vesicle-mediated steroid hormone secretion, while in the long term, hypoxia decreases the expression of genes involved in ecdysone synthesis to delay the ecdysone peak that triggers pupation. We also present evidence that both ecdysone synthesis and secretion are regulated, in part, by NO-signaling. Collectively, our findings reveal that regulated steroid secretion as a critical and environmentally-responsive component of endocrine control, expanding our understanding of how animals integrate growth and developmental timing in response to acute and chronic environmental change. Author SummaryLow oxygen levels (hypoxia) slow growth and development in almost all animals, but how changes in oxygen in the environment are sensed and turned into body-wide hormonal signals is still not well understood. Using Drosophila, we show that oxygen regulates the steroid hormone ecdysone to slow growth and development through two distinct mechanisms: fast hormone release and slower suppression of hormone synthesis. In the short-term, low oxygen triggers the active release of stored ecdysone from the gland that produces it, leading to a rise in circulating hormonal levels that slows body growth. In the longer-term, low oxygen reduces ecdysone production, delaying the hormone peak that initiates pupation and extending overall development. While it is widely accepted that fat-soluble steroids can pass freely, and passively, across membranes, these findings suggest that their active release allows a rapid response to environmental change. More broadly, our work suggests that environmental modulation of steroid secretion, alongside steroid synthesis, may represent a general strategy by which animals coordinate short- and long-term developmental responses to environmental stress.

developmental biology↗

bioRxiv2025

Private QTLs and the Genetic Architecture of Hierarchical Size Traits: From Body Size to Sex-Specific Plasticity

Sex-specific size plasticity (SSP) is the phenomenon whereby the size of one sex is more environmentally sensitive than the other, and is thought to underlie the developmental regulation and evolution of sexual size dimorphism (SSD). Sex-specific plasticity is a higher order phenotype that emerges due to the effect of the environment and sex on core growth regulatory mechanisms. Genetic variation in SSP necessarily requires sex- and environment-specific variation in growth, yet the developmental-genetic mechanisms enabling such context-dependent size variation remain poorly understood. Using a genome-wide association study (GWAS) and functional validation in Drosophila melanogaster, we dissected the genetic architecture of body size, size plasticity, SSD, and SSP across 196 isogenic lineages. We find that each phenotype is governed by largely non-overlapping sets of loci, with most candidate variants lying outside canonical growth pathways. Instead, size trait are shaped by "private QTLs", whose effects are limited to specific sex, trait, or environmental contexts. Functional knockdown of selected candidate genes for SSP revealed that while most did not affect SSP directly, many influenced body size, SSD, and size plasticity, in a manner consistent with their nested phenotypic relationships. Together, our results suggest that context-dependent alleles in genes peripheral to core growth regulatory pathways drive variation in SSD and SSP, offering a mechanistic explanation for their evolutionary lability and highlighting the role of private QTLs in structuring complex trait architecture. Significance StatementSexual size dimorphism (SSD), the differences in body size between females and males, is highly variable among species and yet the developmental genetic mechanisms that generate it and drive its evolution remain elusive. Our work reveals a modular genetic architecture underlying SSD in Drosophila melanogaster, showing that variation in body size, its sex-specific plasticity, and the resulting SSD are controlled by largely non-overlapping, context-dependent loci. This finding provides critical insight into how complex morphological differences between the sexes are genetically organized, allowing for the flexible and independent evolution of hierarchical traits.

evolutionary biology↗

bioRxiv2022

The Genetic Architecture of Morphological Scaling

Morphological scaling relationships between the sizes of individual traits and the body captures the characteristic shape of a species, and the evolution of scaling is the primary mechanism of morphological diversification. However, we have almost no knowledge of the genetic architecture of scaling, critical if we are to understand how scaling evolves. Here we explore the genetic architecture of population-level morphological scaling relationships - the scaling relationship fit to multiple genetically-distinct individuals in a population - by describing the distribution of individual scaling relationships - genotype-specific scaling relationships that are unseen or cryptic. These individual scaling relationships harbor the genetic variation that determines relative trait growth within individuals, and theoretical studies suggest that their distribution dictates how the population scaling relationship will respond to selection. Using variation in nutrition to generate size variation within 197 isogenic lineages of Drosophila melanogaster, we reveal extensive variation in the slopes of the wing-body and leg-body scaling relationships among individual genotypes. This genetic variation reflects variation in the nutritionally-induced size plasticity of the wing, leg and body. Surprisingly, we find that variation in the slope of individual scaling relationships primarily results from variation in nutritionally-induced plasticity of body size, not leg or wing size. These data allow us to predict how different selection regimes alter scaling in Drosophila and is the first step in identifying the genetic targets of such selection. More generally, our approach provides a framework for understanding the genetic architecture of scaling, an important prerequisite to explaining how selection changes scaling and morphology.

genetics↗

bioRxiv2021

PolyA: a tool for adjudicating competing annotations of biological sequences

Annotation of a biological sequence is usually performed by aligning that sequence to a database of known sequence elements. When that database contains elements that are highly similar to each other, the proper annotation may be ambiguous, because several entries in the database produce high-scoring alignments. Typical annotation methods work by assigning a label based on the candidate annotation with the highest alignment score; this can overstate annotation certainty, mislabel boundaries, and fails to identify large scale rearrangements or insertions within the annotated sequence. Here, we present a new software tool, PolyA, that adjudicates between competing alignment-based annotations by computing estimates of annotation confidence, identifying a trace with maximal confidence, and recursively splicing/stitching inserted elements. PolyA communicates annotation certainty, identifies large scale rearrangements, and detects boundaries between neighboring elements.

bioinformatics↗

bioRxiv2020

Ecdysone coordinates plastic growth with robust pattern in the developing wing

Animals develop in unpredictable, variable environments. In response to environmental change some aspects of development adjust to generate plastic phenotypes. Other aspects of development, however, are buffered against environmental change to produce robust phenotypes. How organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we demonstrate that the steroid hormone ecdysone coordinates both plasticity of organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster. Using fed and starved larvae that lack prothoracic glands, which synthesise ecdysone, we show that nutrition regulates growth both via ecdysone and via an ecdysone-independent mechanism, while nutrition regulates patterning only via ecdysone. We then demonstrate that growth shows a graded response to ecdysone concentration, while patterning shows a threshold response. Collectively, these data support a model where nutritionally-regulated ecdysone fluctuations confer plasticity by regulating disc growth in response to basal ecdysone levels, and confers robustness by initiating patterning only once ecdysone peaks exceeds a threshold concentration. This could represent a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.

developmental biology↗