Biology subjects

Shafer, A.

Publications and source records attributed to Shafer, A..

At least 19 recordsLinked to original sources

bioRxiv2026

An updated assessment of the genomic health of Odocoileus

Genomic health estimates help inform conservation and management decisions, with genetic load and runs-of-homozygosity (ROH) being two key metrics. White-tailed deer (Odocoileus virginianus) and mule deer (O. hemionus) are found throughout North America, with some populations declining or of conversation concern. Using genome-wide data from samples across their range, we provide the first estimate of genetic load in mule deer, and revisit ROH estimates using model-based approaches. These updated estimates of ROH notably showed elevated inbreeding in the Key deer, consistent with current conservation designations. We also detected a relatively high number loss-of function mutations in mule deer that we attributed to historical bottlenecks. We also observed an increased overall genetic load in O. hemionus from the Pacific Northwest.

genomics↗

bioRxiv2025

Ancient DNA from the Toronto subway deer adds to the extinction list of North America's Ice Age megafauna

The late Pleistocene was a time of global megafaunal extinctions that were particularly severe in North America. The continent lost many mammal taxa, but the validity of several remain ambiguous, including a high proportion of Cervidae taxa. Torontoceros hypogaeus is represented by a single specimen (ROMM75974) discovered in 1976 during excavation work for the Toronto subway in Canada. The species was described based on its unique antler morphology, but the variable nature of that trait and the species near absence in the fossil record leads to uncertainty concerning its systematic relationships. We used ancient DNA to clarify the taxonomic relationship and evolutionary history of T. hypogaeus. We performed mitochondrial and whole genome analyses with related cervids and showed that ROMM75974 has a close affinity, but relatively high divergence from the Odocoileus sister species. While some ambiguity remains, ROMM75974 could represent a distinct Odocoileus species to be included in the list of extinct North American taxa. This unique population was likely adapted to open landscape which was rapidly replaced with dense woodland in this region at the end of the Pleistocene, highlighting the role of climate change in the extinction of megafauna biodiversity at the end of the ice age.

paleontology↗

bioRxiv2025

Time in sympatry correlates with the strength of reproductive isolation in hybridising Typha

In North America, hybridisation between Typha angustifolia and T. latifolia results in the highly impactful T. x glauca. In Europe, where its parental taxa are also sympatric, T. x glauca is scarce, suggesting stronger reproductive isolation on this continent. Using genomic data from the two species in North America and Europe, we reconstructed their demographic histories and characterised barrier loci between them. Demographic modelling suggests that the initial contact between the two species in Europe occurred [~]800,000 years ago, indicating sympatry in that region since the Middle Pleistocene. In North America, their contact likely happened within the last centuries and was potentially driven by the human-mediated dispersal of T. angustifolia. We identified 47 candidate barrier loci between species in Europe, 6 of which are associated with reproductive functions. No barrier loci were found in North America. Our results suggest that prolonged sympatry can promote the evolution of reproductive barriers, whereas prolonged allopatry can reduce the likelihood of their development. Future studies could help determine whether time in sympatry is a predictor of the strength of reproductive isolation between hybridising taxa. Preventing invasions by hybrid taxa will require limiting the human-mediated dispersal of Typha (and other allopatric species) lacking reproductive isolation.

genomics↗

bioRxiv2025

Environmental Consistency, Not Certainty, Governs Predictive Motor Strategies During Walking

Humans rely on predictive control to maintain stability while walking in dynamic environments, yet the strategies driving this control remain unclear when environments are inconsistent or uncertain. We tested how people adapt to repeated lateral force field disruptions of switching directions, manipulating the force fields Consistency (how often switches occurred) and Certainty (how predictable the switches were). We quantified motor adaptation (error reduction) and sought evidence for two predictive strategies: pattern prediction (detecting a global trial pattern) and carryover prediction (assuming the next trial matches the previous). Adaptation profiles revealed a surprising finding: Consistency, not certainty, drove predictive control. When trials were Consistent, participants pursued appropriate predictive strategies (pattern or carryover). However, when trials were Inconsistent, participants exhibited counterproductive strategies, such as carryover prediction (despite the next trial most often being opposite) or no prediction (despite full certainty of each forthcoming trial). Error reduction was likewise dominated by consistency, with certainty exerting negligible influence. These findings, counter to long-held observations in upper-limb control, suggest the central nervous system faces unique challenges in whole-body control of walking and cannot rely on the simpler adaptation strategies observed in isolated limb control. This raises new, important questions for control of walking and whole-body motor adaptation.

animal behavior and cognition↗

bioRxiv2025

Structural Genomic Variation Underlying Deer Speciation

Speciation is a key driver of biodiversity and understanding its genomic underpinnings can be important for predicting and managing biodiversity. Structural variants (SVs) are large-scale (>50 bp) changes in the genome and have been implicated in adaptive divergence and reproductive isolation. We investigated the role of SVs in the speciation and divergence of two deer species (Odocoileus spp.) across their North American range. Using multiple long-read and a short-read datasets, our bioinformatics workflow revealed SVs and genomic features that were unique to each species. The majority of species-specific SVs were deletions and insertions suggesting that these variants may show higher likelihoods of fixation within populations. Further, while most SVs were intergenic, some genes were impacted, with 3 species-specific SVs showing signs of selection inferred from dN/dS. We also observed a reduced number of regulatory motifs found in fixed SVs compared to the rest of the genome. The SV-affected genes were often associated with reproduction and sensory adaptation, with such functions being relevant to fertility and deer biology and therefore providing insights into potential mechanisms leading to reproductive divergence.

evolutionary biology↗

bioRxiv2025

The heritability of migration behaviours in a wide-ranging ungulate

Migration behaviour is thought to be declining globally in the face of rapid human-mediated environmental change. While many species exhibit individual plasticity in their migratory behaviour, not all species demonstrate the level of plasticity necessary to adjust to novel conditions. Selection on heritable behaviours might therefore play an important role in the maintenance of migratory phenotypes for some species. Using GPS and genomic data from 242 individuals (256 animal-years) in a pedigree-free quantitative genetic approach, we estimated heritability, repeatability, and sources of environmental variation for migration traits in migrating mule deer (Odocoileus hemionus). We also estimated heritability of body size to ensure validity of our results. Heritability estimates of body size traits were comparable to the current estimates for ungulate body size. We found low heritability for broad patterns of migration timing, distance, and duration, but high heritability for movement rate along the migratory route. Our findings suggest that wild mule deer populations have the potential to respond to selection pressure generated by human activity or global environmental changes through microevolutionary changes in migration behaviours. Significance StatementMigration behaviour is critical for the reproduction and survival of a wide variety of taxa, yet there have been global declines in migrations in the face of rapid human-mediated environmental change. Despite our understanding that variation in migration behaviour has both genetic and environmental components, studies quantifying the sources of genetic variation contributing to migration phenotypes are lacking. Our study provides, to our knowledge, the first empirical evidence of heritability in a migration behaviour in ungulates. These results have implications for the evolution and maintenance of migration behaviours in natural populations.

genetics↗

bioRxiv2023

Prior Uncertainty Impedes Discrete Locomotor Adaptation

The impact of environmental uncertainty on locomotor adaptation remains unclear. Environmental uncertainty could either aid locomotor adaptation by prompting protective control strategies that stabilize movements to assist learning or impede adaptation by reducing error sensitivity and fostering hesitance to pursue corrective movements. To explore this, we investigated participants adaptation to a consistent viscous force field after experiencing environmental uncertainty in the form of unpredictable balance perturbations. We compared the performance of this group (Perturbation) to the adaptive performance of a Control group that did not experience any unpredictable perturbations. Perturbations were delivered using a cable-driven robotic device applying lateral forces to the pelvis. We assessed whole-body center of mass (COM) trajectory (COM signed deviation), anticipatory postural adjustments (COM lateral offset), and first step width. The Perturbation group exhibited larger disruptions in COM trajectory (greater COM signed deviations) than the Control group when first walking in the force field. While the COM signed deviations of both groups decreased towards baseline values, only the Control group returned to baseline levels. The Perturbation groups COM signed deviations remained higher, indicating they failed to fully adapt to the force field before the end. The Perturbation group also did not adapt their COM lateral offset to counter the predictable effects of the force field as the Control group did, and their first step width increased more slowly. Our findings suggest that exposure to unpredictable perturbations impeded future sensorimotor adaptations to consistent perturbations.

neuroscience↗

bioRxiv2023

Genomic analyses unveil unprecedented human-induced demographic collapse and recovery in a wide-ranging cervid

The glacial cycles of the Quaternary heavily impacted species through successions of population contractions and expansions. Similarly, populations have been intensely shaped by human pressures such as unregulated hunting and land use changes. White-tailed and mule deer survived in different refugia through the Last Glacial Maximum, and their populations were severely reduced after the European colonisation. Here, we analysed 73 re-sequenced deer genomes from across their North American range to understand the consequences of climatic and anthropogenic pressures on deer demographic and adaptive history. We found a strong signal of glacial-induced vicariance and demographic decline; notably, there is a severe decline in white-tailed deer effective population size (Ne) at the end of the Last Glacial Maximum. We found robust evidence for colonial overharvest in the form of a recent and dramatic drop in Ne in all analysed populations. Historical census size and restocking data show a clear parallel to historical Ne estimates, and temporal Ne/Nc ratio shows patterns of conservation concern for mule deer. Signatures of selection highlight genes related to temperature, including a cold receptor previously highlighted in woolly mammoth. We also detected immune-genes that we surmise reflect the changing land-use patterns in North America. Our study provides a detailed picture of anthropogenic and climatic-induced decline in deer diversity, and clues to understanding the conservation concerns of mule deer and the successful demographic recovery of white-tailed deer.

genomics↗

bioRxiv2023

Stability and Manoeuvrability Interactions During Human Walking Depend on the Manoeuvre Direction

People use the mechanical interplay between stability and manoeuvrability to successfully walk. During single limb support, body states (position and velocity) that increase lateral stability will inherently resist lateral manoeuvres, decrease medial stability, and facilitate medial manoeuvres. Although not well understood, people can make behavioural decisions exploiting this relationship in anticipation of perturbations or direction changes. To characterize the behavioural component of the stability-manoeuvrability relationship, twenty-four participants performed many repetitions of a discrete stepping task involving mid-trial reactive manoeuvres (medial or lateral direction) in a Baseline (no external perturbations) and Perturbed (random mediolateral perturbations applied to their pelvis) environment. We hypothesized people would make systematic changes in lateral stability dependent on both environment (increasing lateral stability in the Perturbed environment) and anticipated manoeuvre direction (reducing lateral stability to facilitate lateral manoeuvres). Participants increased lateral stability in the Perturbed environment, coinciding with an increase in manoeuvre reaction time for laterally but not medially directed manoeuvres. Moreover, we observed lower lateral stability in both environments when people anticipated making a lateral manoeuvre when compared to medial manoeuvres. These results support the hypothesis that people behaviourally exploit the mechanical relationship between lateral stability and manoeuvrability depending on walk task goals and external environment.

bioengineering↗

bioRxiv2023

Leveraging longitudinal diffusion MRI data to quantify differences in white matter microstructural decline in normal and abnormal aging

AbstractO_ST_ABSINTRODUCTIONC_ST_ABSIt is unclear how rates of white matter microstructural decline differ between normal aging and abnormal aging. METHODSDiffusion MRI data from several well-established longitudinal cohorts of aging [Alzheimers Neuroimaging Initiative (ADNI), Baltimore Longitudinal Study of Aging (BLSA), Vanderbilt Memory & Aging Project (VMAP)] was free-water corrected and harmonized. This dataset included 1,723 participants (age at baseline: 72.8{+/-}8.87 years, 49.5% male) and 4,605 imaging sessions (follow-up time: 2.97{+/-}2.09 years, follow-up range: 1-13 years, mean number of visits: 4.42{+/-}1.98). Differences in white matter microstructural decline in normal and abnormal agers was assessed. RESULTSWhile we found global decline in white matter in normal/abnormal aging, we found that several white matter tracts (e.g., cingulum bundle) were vulnerable to abnormal aging. CONCLUSIONSThere is a prevalent role of white matter microstructural decline in aging, and future large-scale studies in this area may further refine our understanding of the underlying neurodegenerative processes. HIGHLIGHTSO_LILongitudinal data was free-water corrected and harmonized C_LIO_LIGlobal effects of white matter decline were seen in normal and abnormal aging C_LIO_LIThe free-water metric was most vulnerable to abnormal aging C_LIO_LICingulum free-water was the most vulnerable to abnormal aging C_LI

neuroscience↗

bioRxiv2023

Development of genomic resources for cattails (Typha), a globally important macrophyte genus

1. BackgroundA critical knowledge gap in freshwater plants research is the lack of genetic tools necessary to answer fundamental questions about their demographic histories, adaptation, and phylogenetic relationships. One example of this is Typha, a global genus of freshwater plants foundational to wetlands that is also becoming an increasingly problematic biological invader in numerous regions worldwide; while important insights have been discovered for this genus, existing markers are insufficient to answer fundamental questions about their demographic histories, adaptation, and phylogenetic relationships, to identify introduced and hybrid lineages, and to examine patterns of hybridisation and introgression. 2. MethodsWe optimised a library preparation and data processing protocol to develop genome-wide nuclear and plastid resources for studying the evolutionary history, genetic structure and diversity, hybridisation, local adaptation, invasiveness, and geographic expansion dynamics of Typha. 3. Main resultsWe sequenced 140 Typha samples and identified [~]120K nuclear SNPs that differentiate T. angustifolia, T. domingensis and T. latifolia and retrieved their plastome sequences. We observed genetic introgression among the three species. 4. ConclusionsFollowing a fast, straightforward, and cost-efficient genomic library preparation protocol, we produced a suite of genome-wide resources to facilitate investigations into the taxonomy and population genetics of Typha and to advance the genomic understanding of wetland plants. 5. ContributionsThe protocol described, the updated chromosome-level genome assembly of T. latifolia, the catalogue of species-specific SNPs, and the chloroplast sequences produced in this study comprise permanent resources that can be applied to study the genetic composition of multiple populations and hybrid zones and will be incorporated into future studies of Typha, an ecologically important and globally invasive macrophyte.

molecular biology↗

bioRxiv2022

Genomic health is dependent on population demographic history

Current genetic methods of population assessment in conservation biology have been challenged by genome-scale analyses due to their quantitatively novel insights. These analyses include assessments of runs-of-homozygosity (ROH), genomic evolutionary rate profiling (GERP), and mutational load. Here, we aim to elucidate the relationships between these measures using three divergent ungulates: the white-tailed deer, caribou, and mountain goat. The white-tailed deer is currently expanding, while caribou are in the midst of a significant decline. Mountain goats remain stable, having suffered a large historical bottleneck. We assessed genome-wide signatures of inbreeding using the inbreeding coefficient F and %ROH (FROH) and identified evolutionarily constrained regions with GERP. Mutational load was estimated by identifying mutations in highly constrained elements (CEs) and sorting intolerant from tolerant (SIFT) mutations. Our results show that F and FROH are higher in mountain goats than in caribou and white-tailed deer. Given the extended bottleneck and low Ne of the mountain goat, this supports the idea that the genome-wide effects of demographic change take time to accrue. Similarly, we found that mountain goats possess more highly constrained CEs and the lowest dN/dS values, both of which are indicative of greater purifying selection; this is also reflected by fewer mutations in CEs and deleterious mutations identified by SIFT. In contrast, white-tailed deer presented the highest mutational load with both metrics, in addition to dN/dS, while caribou were intermediate. Our results demonstrate that extended bottlenecks may lead to reduced diversity and increased FROH in ungulates, but not necessarily the accumulation of deleterious alleles, likely due to the purging of deleterious alleles in small populations.

genomics↗

bioRxiv2022

Short superficial white matter and aging: a longitudinal multi-site study of 1,293 subjects and 2,711 sessions

It is estimated that short association fibers, or "U-shaped" fibers running immediately beneath the cortex, may make up as much as 60% of the total white matter volume. However, these have been understudied relative to the long-range association, projection, and commissural fibers of the brain. This is largely because of limitations of diffusion MRI fiber tractography, which is the primary methodology used to non-invasively study the white matter connections. Inspired by recent anatomical considerations and methodological improvements in U-fiber tractography, we aim to characterize changes in these fiber systems in cognitively normal aging, which provide insight into the biological foundation of age-related cognitive changes, and a better understanding of how age-related pathology differs from healthy aging. To do this, we used three large, longitudinal and cross-sectional datasets (N = 1293 subjects, 2711 sessions) to quantify microstructural features and length/volume features of several U-fiber systems. We find that axial, radial, and mean diffusivities show positive associations with age, while fractional anisotropy has negative associations with age in superficial white matter throughout the entire brain. These associations were most pronounced in the frontal, temporal, and temporoparietal regions. Moreover, measures of U-fiber volume and length decrease with age in a heterogenous manner across the brain, with prominent effects observed for pre- and post-central gyri. These features, and their variations with age, provide the background for characterizing normal aging, and, in combination with larger association pathways and gray matter microstructural features, may provide insight into fundamental mechanisms associated with aging and cognition.

neuroscience↗

bioRxiv2022

Speciation without gene-flow in hybridizing deer

Under the ecological speciation model, divergent selection acts on ecological differences between populations, gradually creating barriers to gene flow and ultimately leading to reproductive isolation. Hybridisation is part of this continuum and can both promote and inhibit the speciation process. Here, we used white-tailed (Odocoileus virginianus) and mule deer (O. hemionus) to investigate patterns of speciation in hybridising sister species. We quantified genome-wide historical introgression and performed genome scans to look for signatures of four different selection scenarios. Despite ample modern evidence of hybridisation, we found negligible patterns of ancestral introgression and no signatures of divergence with gene flow, rather localised patterns of allopatric and balancing selection were detected across the genome. Genes under balancing selection were related to immunity, MHC and sensory perception of smell, the latter of which is consistent with deer biology. The deficiency of historical gene-flow suggests that white-tailed and mule deer were spatially separated during the glaciation cycles of the Pleistocene and genome wide differentiation accrued via genetic drift. Dobzhansky-Muller incompatibilities and selection against hybrids are hypothesised to be acting, and diversity correlations to recombination rates suggests these sister species are far along the speciation continuum.

evolutionary biology↗

bioRxiv2022

Aging and white matter microstructure and macrostructure: a longitudinal multi-site diffusion MRI study of 1,184 participants

Quantifying the microstructural and macrostructural geometrical features of the human brains connections is necessary for understanding normal aging and disease. Here, we examine brain white matter diffusion magnetic resonance imaging data from one cross-sectional and two longitudinal datasets totaling in 1184 subjects and 2236 sessions of people aged 50-97 years. Data was drawn from well-established cohorts, including the Baltimore Longitudinal Study of Aging dataset, Cambridge Centre for Ageing Neuroscience dataset, and the Vanderbilt Memory & Aging Project. Quantifying 4 microstructural features and, for the first time, 11 macrostructure-based features of volume, area, and length across 120 white matter pathways, we apply linear mixed effect modeling to investigate changes in pathway-specific features over time, and document large age associations within white matter. Conventional diffusion tensor microstructure indices are the most age-sensitive measures, with positive age associations for diffusivities and negative age associations with anisotropies, with similar patterns observed across all pathways. Similarly, pathway shape measures also change with age, with negative age associations for most length, surface area, and volume-based features. A particularly novel finding of this study is that while trends were homogeneous throughout the brain for microstructure features, macrostructural features demonstrated heterogeneity across pathways, whereby several projection, thalamic, and commissural tracts exhibited more decline with age compared to association and limbic tracts. The findings from this large-scale study provide a comprehensive overview of the age-related decline in white matter and demonstrate that macrostructural features may be more sensitive to heterogeneous white matter decline. Therefore, leveraging macrostructural features may be useful for studying aging and could have widespread implications for a variety of neurodegenerative disorders.

neuroscience↗

bioRxiv2021

Secondary DNA transfer on denim using a human blood analogue

DNA quantification technology has increased in accuracy and sensitivity, now allowing for detection and profiling of trace DNA. Secondary DNA transfer occurs when DNA is deposited via an intermediary source (e.g. clothing, tools, utensils). Multiple courtrooms have now seen secondary transfer introduced as an explanation for DNA being present at a crime scene, but sparse experimental studies mean expert opinions are often limited. Here, we used bovine blood and indigo denim substrates to quantify the amount of secondary DNA transfer and quality of STRs under three different physical contact scenarios: passive, pressure, and friction. We showed that the DNA transfer was highest under a friction scenario, followed by pressure and passive treatments. The STR profiles showed a similar, albeit less pronounced trend, with correctly scored alleles and genotype completeness being highest under a friction scenario, followed by pressure and passive. DNA on the primary substrate showed a decrease in concentration and genotype completeness both immediately and at 24 hours, suggestive of a loss of DNA during the primary transfer. The majority of secondary transfer samples amplified less than 50% of STR loci regardless of contact type. This study showed that while DNA transfer is common between denim, this is not manifested in full STR profiles. We discuss the possible technical solutions to partial profiles from trace DNA, and more broadly the ubiquity of secondary DNA transfer.

genetics↗

bioRxiv2020

Rational Tuning of CAR Tonic Signaling Yields Superior T-Cell Therapy for Cancer

Chimeric antigen receptors (CARs) are modular proteins capable of redirecting immune cells toward a wide variety of disease-associated antigens. Here, we explore the effects of CAR protein sequence and structure on CAR-T cell function. Based on the empirical observation that CD20 CARs with similar sequences exhibit divergent tonic-signaling and anti-tumor activities, we devised engineering strategies that aimed to improve CAR-T cell function by tuning the intensity of tonic signaling. We found that CARs designed to exhibit low but non-zero levels of tonic signaling show robust effector function upon antigen stimulation while avoiding premature functional exhaustion by CAR-T cells. Through alterations of the CARs ligand-binding domain and overall protein conformation, we generated CD20 CAR variants that outperform the CD19 CAR in mouse models of human lymphoma. We further demonstrate that rational modification of protein confirmation can be generalized to improve GD2 CAR-T cell efficacy against neuroblastoma. These findings point to tonic signaling and basal T-cell activation as informative parameters to guide the rational design of next-generation CARs for cancer therapy.

bioengineering↗

bioRxiv2020

The Biogeography of Dromiciops in Southern South America: middle Miocene transgressions, speciation and associations with Nothofagus

AimSeveral geological events affecting Southern South America during the middle Miocene climatic optimum acted as important drivers of diversification to the biota. This is the case of Microbiotheria, for which Dromiciops is considered the sole surviving lineage, the sister group of Eomarsupialia (Australian marsupials). Three main Dromiciops genetic lineages are known, whose divergence was initially attributed to recent Pleistocene glaciations. Using fossil-calibrated dating on nuclear and mitochondrial genes, here we reevaluate this hypothesis and report an older (Miocenic) biogeographic history for the genus. LocationSouthern South America. MethodsPhylogenetic reconstruction using sequences from two mitochondrial DNA and four nuclear DNA genes in 159 specimens, from 31 sites across Chile and Argentina. Divergence time estimation using fossil calibration. ResultsOur phylogenetic analysis resolved four well supported clades with discrete geographic distributions. The oldest and most differentiated clade corresponds to that of the northern distribution (35.2{degrees}S to 39.3{degrees}S), which would be a different species (D. bozinovici, sensu Delia et al. 2016). According to our estimations, this species shared a common ancestor with D. gliroides (southern clades) about 13 million years ago (95% CI: 6.4-25.3). The southern clades (39.6{degrees}S to 42.0{degrees}S), showed a divergence time ranging from 9.57 to 6.5 Mya. Strong genetic structure was detected from north to south but not across the Andes, or between Chiloe island/ mainland. Demographic equilibrium is inferred to the northern clade, and recent demographic expansions was detected in the central and southern clades. Main conclusionsThe whole diversification of Dromiciops occurred within the Miocene, being the Middle Miocene transgression (MMT), the massive marine flooding that covered several lowlands of the western face of los Andes between 38-48{degrees} S, the most likely diversifying force. This was the result of an increase in global sea levels due to the Miocene climatic optimum, which shaped the biogeographic origin of several species, including Nothofagus forests, the habitat main of Dromiciops.

evolutionary biology↗