Biology subjects

Durkin, S. M.

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

5 recordsLinked to original sources

bioRxiv2026

A maternal effect shapes early-life adaptive body size variation in house mice

Almost all phenotypic variation is mediated by a combination of genetic and environmental effects. Importantly, the balance of these effects can fluctuate over an organisms lifespan, with the maternal environment being particularly important during early life, especially in mammals. Using house mice as a model, we combine behavioral, molecular, and quantitative genetic approaches to understand how genetic and maternal variation together shape phenotypic divergence in a classic example of morphological adaptation. Temperate house mice are larger than tropical house mice, conforming to Bergmanns rule. We find that cross-fostering leads to pronounced weight restriction in cold-adapted, large-bodied mice, revealing an important effect of maternal environment. We then describe the molecular underpinnings of genetic and maternal influences on weight by identifying both the genetically- and maternally-controlled differences in gene expression in liver, a key tissue regulating growth. Maternally plastic expression variation is largely controlled in trans-, while stable, genetic variation is mediated in cis-. Additionally, we link maternally-controlled expression variation in growth-restricted mice to known nutrient deficiency signaling pathways. Finally, we identify candidate loci underlying the genetic basis of adaptive body size divergence from a combination of selection scans in wild populations and cis-regulated genes that overlap QTL identified in a mapping panel of temperate and tropical mice. Collectively, these results provide insight into how genetic and environmental forces influence adaptive phenotypic divergence in the context of a critical developmental window. SIGNIFICANCEAdaptive phenotypes arise from both genetic and environmental influences, yet their unique contributions are rarely resolved within the same natural system. Using locally-adapted house mice that conform to Bergmanns rule, we experimentally disentangled the genetic and plastic determinants of adaptive body size, focusing on the maternal environment. A maternal effect explains the majority of body weight variation during nursing and is linked to transcriptional changes in nutrient sensing pathways. By separating maternally- and genetically-determined transcriptional variation, we revealed distinct regulatory architectures for plastic and stable expression and identified candidate genes underlying adaptive body size divergence. This work offers broad insight into adaptive evolution and specific details on the mechanistic basis of one of the most widespread ecogeographic patterns in nature.

evolutionary biology↗

bioRxiv2025

Regionally specific and highly pleiotropic loci together mediate skeletal evolution in tropical and temperate house mice

When organisms are exposed to new environments, they often evolve a suite of adaptive phenotypic changes. Understanding the genetic basis of these changes gives us insight into the factors that constrain and facilitate the process of adaptation. Here we use quantitative trait locus (QTL) mapping in wild-derived house mice from temperate and tropical environments to describe the genetic architecture of adaptive skeletal evolution. This study provides a unique view into the evolution of discordant phenotypic changes within the interconnected skeletal system, since tropical and temperate mice have evolved under the opposing forces of Allens and Bergmanns rules (shorter extremities, but larger body size in cold climates). We generated an F3 mapping population of 449 mice and measured a variety of cranial and post-cranial skeletal traits. First, we discovered that temperate and tropical house mice have undergone extensive skeletal divergence in accordance with Allens and Bergmanns rules. Warm-adapted mice have longer limbs, longer pelvic girdles, longer and narrower skulls, but smaller overall body size. Second, we identified 83 QTL across 13 traits and found that the genetic basis of skeletal divergence involved mainly additive, small-effect loci distributed across the genome. While most QTL influenced only one or two traits, we also identified several highly pleiotropic QTL that influenced multiple traits across the skeletal system, often antagonistically to the evolved difference. Such pleiotropic loci may constrain adaptation. Lastly, we found that QTL for overall skeletal variation were enriched for signatures of selection in wild house mouse populations, providing evidence that skeletal variation in this system is indeed driven by adaptive evolution. Article SummaryThe incredible diversity of the vertebrate skeleton offers an opportunity to explore the genetic architecture of phenotypic variation, which is essential to understanding the process of evolution. We characterize the genetic basis of morphological evolution using QTL mapping in house mice adapted to differing climates. Skeletal divergence is widespread in these mice and reflects temperature adaptation. This divergence is mediated by small-effect loci scattered across the genome, as well as several highly-pleiotropic loci. Interestingly, pleiotropic loci often influence phenotypes in the opposite direction from the evolved change, perhaps constraining the process of adaptation. This work demonstrates how complex morphological changes can evolve within an interconnected system, such as the skeleton, under functional, developmental, and selective constraints.

evolutionary biology↗

bioRxiv2023

The evolution and mutational robustness of chromatin accessibility in Drosophila

The evolution of regulatory regions in the genome plays a critical role in shaping the diversity of life. While this process is primarily sequence-dependent, the enormous complexity of biological systems has made it difficult to understand the factors underlying regulation and its evolution. Here, we apply deep neural networks as a tool to investigate the sequence determinants underlying chromatin accessibility in different tissues of Drosophila. We train hybrid convolution-attention neural networks to accurately predict ATAC-seq peaks using only local DNA sequences as input. We show that a model trained in one species has nearly identical performance when tested in another species, implying that the sequence determinants of accessibility are highly conserved. Indeed, model performance remains excellent even in distantly-related species. By using our model to examine species-specific gains in chromatin accessibility, we find that their orthologous inaccessible regions in other species have surprisingly similar model outputs, suggesting that these regions may be ancestrally poised for evolution. We then use in silico saturation mutagenesis to reveal evidence of selective constraint acting specifically on inaccessible chromatin regions. We further show that chromatin accessibility can be accurately predicted from short subsequences in each example. However, in silico knock-out of these sequences does not qualitatively impair classification, implying that chromatin accessibility is mutationally robust. Subsequently, we demonstrate that chromatin accessibility is predicted to be robust to large-scale random mutation even in the absence of selection. We also perform in silico evolution experiments under the regime of strong selection and weak mutation (SSWM) and show that chromatin accessibility can be extremely malleable despite its mutational robustness. However, selection acting in different directions in a tissue-specific manner can substantially slow adaptation. Finally, we identify motifs predictive of chromatin accessibility and recover motifs corresponding to known chromatin accessibility activators and repressors. These results demonstrate the conservation of the sequence determinants of accessibility and the general robustness of chromatin accessibility, as well as the power of deep neural networks as tools to answer fundamental questions in regulatory genomics and evolution.

evolutionary biology↗

bioRxiv2022

Environmentally robust cis-regulatory changes underlie rapid climatic adaptation

Changes in gene expression are proposed to play a major role in adaptive evolution. While it is known that gene expression is highly sensitive to the environment, very few studies have determined the influence of genetic and environmental effects on adaptive gene regulation in natural populations. Here, we utilize allele-specific expression to characterize cis and trans gene regulatory divergence in temperate and tropical house mice in two metabolic tissues under two thermal conditions. First, we show that gene expression divergence is pervasive between populations and across thermal conditions, with roughly 5-10% of genes exhibiting genotype-by-environment interactions. Second, we found that most expression divergence was due to cis-regulatory changes that were stable across temperatures. In contrast, patterns of expression plasticity were largely attributable to trans-effects, which showed greater sensitivity to temperature. Nonetheless, we discovered a small subset of temperature-dependent cis-regulatory changes, thereby identifying loci underlying expression plasticity. Finally, we performed scans for selection in wild house mice to identify genomic signatures of rapid adaptation. Genomic outliers were enriched in genes with evidence for cis-regulatory divergence. Notably, these genes were associated with phenotypes that affected body weight and metabolism, suggesting that cis-regulatory changes are a possible mechanism for adaptive body size evolution between populations. Our results show that gene expression plasticity, largely controlled in trans, may facilitate the colonization of new environments, but that evolved changes in gene expression are largely controlled in cis, illustrating the genetic and non-genetic mechanisms underlying the establishment of populations in new environments. Significance StatementGene expression variation is shaped by both genetic and environmental effects, yet these two factors are rarely considered together in the context of adaptive evolution. We studied environmental influences on gene regulatory evolution in temperate and tropical house mice in cold and warm laboratory environments. We discovered that genetic effects in the form of cis-regulatory divergence were pervasive and largely insensitive to the environment. Many of these genetic effects are under selection and are associated with genes that affect body size, suggesting cis-regulatory changes as a possible mechanism for adaptive body size evolution. We also discovered many trans-effects controlling expression plasticity, demonstrating the importance of both genetic and non-genetic changes associated with adaptation over short timescales (a few hundred generations).

evolutionary biology↗

bioRxiv2020

Behavioral and genomic sensory adaptations underlying the pest activity of Drosophila suzukii

Studying how novel phenotypes originate and evolve is fundamental to the field of evolutionary biology as it allows us to understand how organismal diversity is generated and maintained. However, determining the basis of novel phenotypes is challenging as it involves orchestrated changes at multiple biological levels. Here, we aim to overcome this challenge by using a comparative species framework combining behavioral, gene expression, and genomic analyses to understand the evolutionary novel egg-laying substrate-choice behavior of the invasive pest species Drosophila suzukii. First, we used egg-laying behavioral assays to understand the evolution of ripe fruit oviposition preference in D. suzukii as compared to closely related species D. subpulchrella and D. biarmipes, as well as D. melanogaster. We show that D. subpulchrella and D. biarmipes lay eggs on both ripe and rotten fruits, suggesting that the transition to ripe fruit preference was gradual. Secondly, using two-choice oviposition assays, we studied how D. suzukii, D. subpulchrella, D. biarmipes and D. melanogaster differentially process key sensory cues distinguishing ripe from rotten fruit during egg-laying. We found that D. suzukiis preference for ripe fruit is in part mediated through a species-specific preference for stiff substrates. Lastly, we sequenced and annotated a high-quality genome for D. subpulchrella. Using comparative genomic approaches, we identified candidate genes involved in D. suzukiis ability to seek out and target ripe fruits. Our results provide detail to the stepwise evolution of pest activity in D. suzukii, indicating important cues used by this species when finding a host, and the molecular mechanisms potentially underlying their adaptation to a new ecological niche.

evolutionary biology↗