Biology subjects

Anderson, J. T.

Publications and source records attributed to Anderson, J. T..

8 recordsLinked to original sources

bioRxiv2026

Co-Circulation of Multiple Kolmioviridae Lineages Through Vertebrate Evolution

Although once only characterized by human hepatitis deltavirus (HDV), membership of the family Kolmioviridae has dramatically expanded in recent years. Despite this transformation in our understanding of the host range of kolmioviruses, the evolutionary history of this enigmatic group of RNA viruses is unclear. Kolmioviruses are characterized as small ([~]1.7kb) satellite viruses that encode a single [~]200 amino acid delta antigen (DAg) and require unrelated helper viruses for replication. Here, we describe eight novel kolmioviruses from metatranscriptomic studies of the American alligator (Alligator missippiensis), red kangaroo (Osphranter rufus), and central bearded dragon (Pogona vitticeps), as well as avian kolmioviruses mined from the Sequence Read Archive (SRA). Although the novel kolmioviruses were often found in samples co-infected by other viruses, there was no evidence for the presence of hepatitis B virus as seen in HDV. By employing a range of sequence data sets, alignment methods, alignment trimming methods, and substitution models, we provide an evolutionary history of the Kolmioviridae that maximizes the extent of virus-host co-divergence and refines estimates of their evolutionary timescale. Although DAg amino acid sequences are more conserved than nucleotide sequences and hence might be expected to result in more accurate phylogenetic trees, we show that full genome nucleotide sequences likely provide the best representation of kolmiovirus evolution. More broadly, our results reveal that irrespective of the data set used, multiple distinct kolmiovirus lineages have co-circulated throughout vertebrate evolution over timescales spanning hundreds of millions of years, with the association between HDV and HBV appearing only recently. Significance StatementKolmioviruses are satellite RNA viruses, with hepatitis deltavirus (HDV) associated with human disease following co-infection with hepatitis B virus (HBV) the best characterized. Although a growing number of animal kolmioviruses have been identified in metagenomic studies and associated with a range of helper viruses, the evolutionary origins and history of this important and unique group of viruses is unknown. By identifying novel kolmioviruses in a range vertebrate hosts, including American alligators, we show that highly diverse lineages of kolmioviruses have co-circulated for the duration of vertebrate evolution with clear evidence of virus-host co-divergence, and are associated with a variety of potential helper viruses. Despite this antiquity, we present evidence that the HDV-HBV association only recently evolved in human populations.

microbiology↗

bioRxiv2025

Two decades of resurrection studies: What have we learned about contemporary evolution of plant species?

Global change has profoundly altered the eco-evolutionary trajectories of plant species. Longitudinal studies often document phenotypic shifts in response to climate change, such as earlier flowering in the spring, but it remains challenging to disentangle the contributions of phenotypic plasticity and adaptive evolution to shifted phenotypic distributions. The resurrection approach has emerged as a powerful method to study genetic and plastic responses to novel selection imposed by global change by contrasting ancestral and descendant lineages from the same population under common conditions. Here, we compiled a database of 52 resurrection studies to examine key hypotheses about plant evolutionary responses to global change using a meta-analysis (40 of the studies) and quantitative review (all 52 studies). We found evidence for rapid, contemporary evolution, which often appeared adaptive, in over half of the cases, including some of the fastest cases of evolution in natural populations ever observed. Annual plants evolved earlier reproduction, and leaf economic traits associated with stress escape strategies. We also found evolution of increased plasticity for annual plants in phenology and physiology traits, and a reduction of plasticity in traits related to the leaf economic spectrum. We found less evidence for evolution in perennial species. Overall, our findings demonstrate the key role of drought escape in plant responses to a warming world. However, the lack of evolution in other traits and species indicates that constraints may dampen evolutionary responses in some scenarios. Our review also suggests promising avenues of future research for resurrection studies.

evolutionary biology↗

bioRxiv2023

SPINAL V1 INHIBITORY INTERNEURON CLADES DIFFER IN BIRTHDATE, PROJECTIONS TO MOTONEURONS AND HETEROGENEITY

Spinal cord interneurons play critical roles shaping motor output, but their precise identity and connectivity remain unclear. Focusing on the V1 interneuron cardinal class we defined four major V1 subsets according to neurogenesis timing, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Birthdate delineates two early born (Renshaw and Pou6f2) and two late born (Foxp2 and Sp8) V1 clades, showing that sequential neurogenesis produces different V1 subsets. Early born Renshaw cells and late born Foxp2-V1 interneurons are tightly coupled to motoneurons, while early born Pou6f2-V1 and late born Sp8-V1 interneurons are not, indicating that timing of neurogenesis does not correlate with motoneuron targeting. V1 clades also differ in cell numbers and diversity. Lineage labeling shows that the Foxp2-V1 clade contains over half of all V1 interneurons, provides the largest inhibitory input to motoneuron cell bodies and includes subgroups that differ in birthdate, location, and proprioceptive input. Notably, one Foxp2-V1 subgroup, defined by postnatal Otp expression is positioned near the lateral motor column and receives substantial input from proprioceptors, consistent with an involvement in reciprocal inhibitory pathways. Combined tracing of ankle flexor sensory afferents and interneurons monosynaptically connected to ankle extensors confirmed placement of Foxp2-V1 interneurons in reciprocal inhibitory pathways. Our results validate previously proposed V1 clades as unique functional subtypes that differ in circuit placement, with Foxp2-V1 cells forming the most heterogeneous subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for their diverse ontogenetic and phylogenetic origins. SIGNIFICANCE STATEMENTThe complexity of spinal interneuron diversity and circuit organization represents a challenge to understand neural control of movement in normal adults as well as during motor development and in disease. Inhibitory interneurons are a core element of these spinal circuits. V1 interneurons comprise the largest group of inhibitory interneurons in the ventral horn, and their organization remains unclear. Here we present a comprehensive examination of V1 subtypes according to neurogenesis, placement in spinal motor circuits, and motoneuron synaptic targeting. V1 diversity increases during evolution from axial-swimming fishes to limb-based mammalian terrestrial locomotion. This increased diversity is reflected in the size and heterogeneity of the Foxp2-V1 clade, a group closely associated with limb motor pools. We show that Foxp2-V1 interneurons establish the densest direct inhibitory input to motoneurons, especially on cell bodies. These findings are particularly significant because recent studies have shown that motor neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) affect inhibitory V1 synapses on motoneuron cell bodies and Foxp2-V1 interneurons themselves in the earliest stages of pathology.

neuroscience↗

bioRxiv2023

Sortilin inhibition treats multiple neurodegenerative lysosomal storage disorders.

Lysosomal storage disorders (LSDs) are a genetically and clinically diverse group of diseases characterized by lysosomal dysfunction. Batten disease is a family of severe LSDs primarily impacting the central nervous system. Here we show that AF38469, a small molecule inhibitor of sortilin, improves lysosomal and glial pathology across multiple LSD models. Live-cell imaging and comparative transcriptomics demonstrates that the transcription factor EB (TFEB), an upstream regulator of lysosomal biogenesis, is activated upon treatment with AF38469. Utilizing CLN2 and CLN3 Batten disease mouse models, we performed a short-term efficacy study and show that treatment with AF38469 prevents the accumulation of lysosomal storage material and the development of neuroinflammation, key disease associated pathologies. Tremor phenotypes, an early behavioral phenotype in the CLN2 disease model, were also completely rescued. These findings reveal sortilin inhibition as a novel and highly efficacious therapeutic modality for the treatment of multiple forms of Batten disease.

neuroscience↗

bioRxiv2022

bII-spectrin is required for synaptic positioning during retinal development

Neural circuit assembly is a multi-step process where synaptic partners are often born at distinct developmental stages, and yet they must find each other and form precise synaptic connections with one another. This developmental process often relies on late-born neurons extending their processes to the appropriate layer to find and make synaptic connections to their early-born targets. The molecular mechanism responsible for the integration of late-born neurons into an emerging neural circuit remains unclear. Here we uncovered a new role for the cytoskeletal protein {beta}II-spectrin in properly positioning pre- and post-synaptic neurons to the developing synaptic layer. Loss of {beta}II-spectrin disrupts retinal lamination, leads to synaptic connectivity defects, and results in impaired visual function. Together, these findings highlight a new function of {beta}II-spectrin in assembling neural circuits in the mouse outer retina. HighlightsO_LIEstablished a new role for {beta}II-spectrin in assembling retinal circuits C_LIO_LI{beta}II-spectrin positions pre- and post-synaptic neurons to the developing synaptic layer C_LIO_LIEarly positioning of processes to the OPL is required for synaptogenesis C_LIO_LILoss of {beta}II-spectrin disrupts synaptic connectivity and impairs visual function C_LI

neuroscience↗

bioRxiv2022

Gut Microbial Trimethylamine is Elevated in Alcohol-Associated Hepatitis and Contributes to Ethanol-Induced Liver Injury in Mice

BACKGROUNDThere is mounting evidence that microbes resident in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. METHODSWe used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. RESULTSWe show the gut microbial choline metabolite trimethylamine (TMA) is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. CONCLUSIONSThe microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.

biochemistry↗

bioRxiv2020

Gut Microbe-Targeted Choline Trimethylamine Lyase Inhibition Improves Obesity Via Rewiring of Host Circadian Rhythms

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (ob/ob). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake, but is instead associated with beneficial remodeling of the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism, and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have untapped potential as anti-obesity therapeutics.

physiology↗

bioRxiv2017

Phenological responses to multiple environmental drivers under climate change: insights from a long-term observational study and a manipulative field experiment

Climate change has induced pronounced shifts in the reproductive phenology of plants, with the timing of first flowering advancing in most species. Indeed, population persistence may be threatened by the inability to track climate change phenologically. Nevertheless, substantial variation exists in biological responses to climate change across taxa. Here, we explore the consequences of climate change for flowering phenology by integrating data from a long-term observational study and a manipulative experiment under contemporary conditions. Dissecting the environmental factors that influence phenological change will illuminate why interspecific variation exists in responses to climate change. We examine a 43-year record of first flowering for six species in subalpine meadows of Colorado in conjunction with a 3-year snow manipulation experiment on the perennial mustard Boechera stricta from the same site. We analyze shifts in the onset of flowering in relation to environmental drivers known to influence phenology: the timing of snowmelt, the accumulation of growing degree days, and photoperiod. At our study site, climate change is reducing snowpack and advancing the timing of spring snowmelt. We found that variation in phenological responses to climate change depended on the sequence in which species flowered, with early-flowering species flowering faster, at a lower heat sum, and under increasingly disparate photoperiods in comparison to species that flower later in the season. Furthermore, climate change is outpacing phenological change for all species. Early snow removal treatments confirm that the timing of snowmelt governs observed trends in flowering phenology of B. stricta and that climate change can reduce the probability of flowering, thereby depressing fitness. Shorter-term studies would not have captured the trends that we document in our observational and experimental datasets. Accurate predictions of the biological responses to climate change require a thorough understanding of the specific environmental factors driving shifts in phenology.

ecology↗