Biology subjects

Suvorov, A.

Publications and source records attributed to Suvorov, A..

16 recordsLinked to original sources

bioRxiv2026

Testing Thirty Years of Hypotheses: Ancient Trout-Salmon Introgression and Limited Pre-Colonial Gene Flow Between Rainbow and Cutthroat Trout Shaped Pacific Salmonid Evolution

Introgression is the transfer of genetic material between species or populations through hybridization and backcrossing. While often deleterious or neutral in nature, introgression can also have beneficial consequences for the recipient lineage. Oncorhynchus is a genus of ray-finned fish (family Salmonidae) composed of nine species of Pacific trout and eight species of Pacific salmon, in which deep introgression has long been proposed to explain patterns of gene-tree-species-tree discordance, and in which hybridization is extensively observed between introduced and endemic species. In this study, we identified well-supported introgression between the ancestral lineage of Pacific trout and the ancestor of Chinook and coho salmon, a long-posited but previously untested hypothesis. While other salmon lineages (pink, chum, sockeye, and masu salmon) have been sympatric with trout for extended periods, providing an opportunity for hybridization to occur, we found no evidence of introgression between trout and these other salmon lineages. Our findings suggest mito-nuclear incompatibilities serve as a possible barrier to gene flow between the clade comprised of pink, chum, and sockeye salmon and all other lineages in Oncorhynchus. Within Pacific trout, we detected no historical introgression between cutthroat and rainbow trout lineages, suggesting that the extensive hybridization observed between them today reflects recent, primarily human-mediated contact rather than long-term gene flow. These findings show that ancestral introgression has shaped the evolutionary history of Oncorhynchus and should be accounted for in future comparative phylogenetic studies of the genus.

evolutionary biology↗

bioRxiv2026

Small-molecule IGF1R inhibitors extend healthspan in a mouse model

Antagonistic pleiotropy of the IGF-1 signaling cascade is well recognized, as it promotes growth and development at younger ages and delays aging later in life. The goal of this study is to test in a mouse longevity experiment whether orally delivered small-molecule IGF1R inhibitors have promise as an anti-aging therapy. C57BL/6 mice (25 male and 25 female mice per treatment) were treated with selective IGF1R inhibitors, picropodophyllin (PPP) or 5-[3-(phenylmethoxy)phenyl]-7-[trans-3-(1-pyrrolidinylmethyl)cyclobutyl]-7H-pyrrolo[3-d]pyrimidin-4-amine (NVP-ADW742), via powdered diets starting at 13 months of age, and physiological and behavioral parameters, as well as survival, were assessed. Both compounds protected both sexes from short-term memory decline; reduced systolic blood pressure in males and pulse rate in both sexes; rescued declining glucose tolerance in males; and abolished grey hair development, reduced frailty, and protected against decline in grip strength in female mice. There were no sex differences in survival curves within groups. No significant differences between groups were observed in the Kaplan-Meier analysis. However, the survival curve in the NVP-ADW742 group was "squarer" than in controls, indicating a 93-day longer healthspan (p = 0.02). PPP treatment was associated with toxicity (GI bleeding). Additional analysis of the drug likeness of NVP-ADW742 demonstrated potential cardiotoxicity and brain bioaccumulation. To conclude, small-molecule IGF1R inhibitors hold promise as a therapy that may improve human health span and lifespan; however, both molecules tested in this study have side effects that may outweigh their anti-aging effects. Statements and DeclarationsYB is an employee of ReGENE LLC. GB received compensation from ReGENE LLC as a consultant. CJE received compensation from and is a member of ReGENE LLC. AS received compensation from and is a member of ReGENE LLC. TS declares no conflict of interest.

developmental biology↗

bioRxiv2025

GhostParser: A highly scalable phylogenomic approach for the identification of ghost introgression

A growing body of empirical research shows that interspecific gene flow is a widespread biological force that shapes evolutionary histories across the Tree of Life. Computational approaches designed to detect introgression either employ full likelihood, including Bayesian, frameworks to directly estimate phylogenetic networks or utilize summary statistics derived directly from locus sequence alignments or estimated gene trees to map gene flow events onto the species tree. Many current methods currently have major shortcomings. The computationally scalable summary statistics and pseudo-likelihood-based techniques may provide erroneous results in the presence of so-called "ghost" introgression and rate variation between lineages. On the other hand, full likelihood methods are more accurate, but are not computationally tractable for large phylogenomic datasets. Here, we develop a novel summary statistic, based on tree heights of different gene tree topologies to reliably distinguish between sampled and ghost introgression events. We implemented this approach in the publicly accessible bioinformatic pipeline "GhostParser". We demonstrate that GhostParser can accurately distinguish between scenarios of sampled and ghost introgression, even in the presence of rate variation between lineages. Our methodology generally concurs in accuracy with the full likelihood software Bayesian Phylogenetics and Phylogeography (BPP) on empirical datasets, and outperforms BPP in our simulation conditions, both in a small fraction of the computational time. We show that GhostParser is a scalable tool for the identification of different introgression patterns in phylogenomic datasets.

bioinformatics↗

bioRxiv2025

Mechanistic target of rapamycin/blood-testes barrier mechanism mediates acceleration of sperm epigenetic aging by environmental factors

Our previous research suggested that mechanistic target of rapamycin (mTOR)/blood-testis barrier (BTB) mechanism is involved in the regulation of the rates of epigenetic aging of sperm, where increased activity of mTORC1 opens BTB and accelerates epigenetic aging and increased activity of mTORC2 produces opposite results - increases BTB integrity and rejuvenates sperm epigenome. In the present study, we use our newly developed epigenetic clock model to investigate whether the mTOR/BTB mechanism is involved in the epigenetic reprogramming of sperm in mice exposed to heat stress (HS) and cadmium (Cd). Our findings show that both mTOR-dependent BTB disruption caused by HS and mTOR-independent BTB disruption due to Cd exposure accelerate sperm epigenetic aging, resulting in similar changes to sperm DNA methylation patterns. These results suggest that the mTOR/BTB mechanism is a novel molecular pathway through which environmental stressors influence sperm epigenetic aging, and this pathway may be relevant to a broad range of factors, including environmental, lifestyle, dietary, and health influences.

molecular biology↗

bioRxiv2024

Elevational and Oceanic Barriers Shape the Distribution, Dispersal and Diversity of Aotearoa's Kapokapowai (Uropetala) Dragonflies

Mountains and islands provide an opportunity for studying the biogeography of diversification and population fragmentation. Aotearoa (New Zealand) is an excellent location to investigate both phenomena due to alpine emergence and oceanic separation. While it would be expected that separation across oceanic and elevation gradients are major barriers to gene flow in animals, including aquatic insects, such hypotheses have not been thoroughly tested in these taxa. By integrating population genomic from sub-genomic Anchored-Hybrid Enrichment sequencing, ecological niche modeling, and morphological analyses from scanning-electron microscopy, we show that tectonic uplift and oceanic vicariance are implicated in speciation and population structure in Kapokapowai (Uropetala) dragonflies. Although Te Moana o Raukawa (Cook Strait), is likely responsible for some of the genetic structure observed, speciation has not yet occurred in populations separated by the strait. We find that the altitudinal gradient across K[a] Tiritiri-o-te-Moana (the Southern Alps) is not impervious but it significantly restricts gene flow between aforementioned species. Our data support the hypothesis of an active colonization of K[a] Tiritiri-o-te-Moana by the ancestral population of Kapokapowai, followed by a recolonization of the lowlands. These findings provide key foundations for the study of lineages endemic to Aotearoa.

evolutionary biology↗

bioRxiv2024

Molecular Basis of Sperm Methylome Response to Aging and Stress

Changes in the sperm epigenome induced by age and/or stressors often follow common unexplained patterns affecting genes responsible for embryonic development and neurodevelopment. The stochastic epigenetic variation (SEV) hypothesis proposes that in response to stressors naturally variable methylation regions (VMRs) associated with morphogenic genes increase in methylation variation to diversify phenotypes and improve chances of survival of the genetic lineage. Here, we test predictions from the SEV hypothesis using mouse and rat sperm DNA methylation and other -omics data. We demonstrate that the context of DNA regions determines the response of sperm methylome to various factors rather than the stressors and/or timing of these factors. We propose a model explaining age/stress-dependent shifts in methylation in VMRs by an asymmetric increase in methylation variation of these regions. Because methylation variation in VMRs increases with age, sperm methylome response to stressors may be characterized as an acceleration of epigenetic aging.

systems biology↗

bioRxiv2024

Developmental Reprogramming of Hypothalamic-Pituitary Axis in Mice by Common Environmental Pollutants

Humans are exposed to a large number of endocrine disrupting chemicals (EDCs). Many studies demonstrated that exposures to EDCs during critical windows of development can permanently affect endocrine health outcomes. Most of experimental studies address changes in secretion of hormones produced by gonads, thyroid gland and adrenals, and little is known about the ability of EDCs to produce long-term changes in the hypothalamic-pituitary (HP) control axes. Here, we examined the long-term effects of three common EDCs on male mouse HP gene expression, following developmental exposures. Pregnant mice were exposed to 0.2 mg/ml solutions of bisphenol S (BPS), 2,2,4,4-tetrabromodiphenyl ether (BDE-47), or 3,3,5,5-tetrabromobisphenol A (TBBPA) from pregnancy day 8 through lactation day 21 (weaning day). Male offspring were left untreated until postnatal day 140, where pituitaries and hypothalami were collected. Pituitaries were assed for gene expression via RNA sequencing, while specific genes were assessed for expression in hypothalami via RT-qPCR. Differential expression, as well as gene enrichment and pathway analysis, indicated that all three chemicals induced long-term changes, (mostly suppression) in pituitary genes involved in its endocrine function. BPS and BDE-47 produced effects overlapping significantly at the level of effected genes and pathways. All three chemicals altered genes and pathways of gonad and liver HP axes, while BPS altered HP-adrenal and BDE-47 altered HP-thyroid pathways specifically. All three chemicals also reduced expression of immune genes in the pituitaries. Targeted gene expression in the hypothalamus indicates a down regulation of hypothalamic endocrine control genes by BPS and BDE-47 groups, concordant with changes in the pituitary and suggests that these chemicals suppress the overall HP endocrine function. Interestingly, all three chemicals altered pituitary genes of GPCR-mediated intracellular signaling molecules, many of which are key signalers common to many pituitary responses to hormones. The results of this study show that developmental exposures to common and ubiquitous EDCs have long-term impacts on hormonal feedback control at the hypothalamic-pituitary level.

pharmacology and toxicology↗

bioRxiv2023

Single-fly assemblies fill major phylogenomic gaps across the Drosophilidae Tree of Life

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab. Here, we build upon our previous methods to perform amplification-free ONT sequencing of single wild flies obtained either directly from the field or from ethanol-preserved specimens in museum collections, greatly improving the representation of lesser studied drosophilid taxa in whole-genome data. Using Illumina Novaseq X Plus and ONT P2 sequencers with R10.4.1 chemistry, we set a new benchmark for inexpensive hybrid genome assembly at US $150 per genome while assembling genomes from as little as 35 ng of genomic DNA from a single fly. We present 183 new genome assemblies for 179 species as a resource for drosophilid systematics, phylogenetics, and comparative genomics. Of these genomes, 62 are from pooled lab strains and 121 from single adult flies. Despite the sample limitations of working with small insects, most single-fly diploid assemblies are comparable in contiguity (>1Mb contig N50), completeness (>98% complete dipteran BUSCOs), and accuracy (>QV40 genome-wide with ONT R10.4.1) to assemblies from inbred lines. We present a well-resolved multi-locus phylogeny for 360 drosophilid and 4 outgroup species encompassing all publicly available (as of August 2023) genomes for this group. Finally, we present a Progressive Cactus whole-genome, reference-free alignment built from a subset of 298 suitably high-quality drosophilid genomes. The new assemblies and alignment, along with updated laboratory protocols and computational pipelines, are released as an open resource and as a tool for studying evolution at the scale of an entire insect family.

evolutionary biology↗

bioRxiv2023

Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation

Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at the time of conception. Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. The mechanism(s) linking paternal age with epigenetic changes in sperm remain unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB is regulated by the balance of two mTOR complexes in Sertoli cells where mTOR complex 1 (mTORC1) promotes the opening of the BTB and mTOR complex 2 (mTORC2) promotes its integrity. We hypothesized that this balance is also responsible for age-dependent changes in the sperm epigenome. To test this hypothesis, we analyzed reproductive outcomes, including sperm DNA methylation in transgenic mice with Sertoli cell-specific suppression of mTORC1 (Raptor KO) or mTORC2 (Rictor KO). mTORC2 suppression accelerated aging of the sperm DNA methylome and resulted in a reproductive phenotype concordant with older age, including decreased testes weight and sperm counts, and increased percent of morphologically abnormal spermatozoa and mitochondrial DNA copy number. Suppression of mTORC1 resulted in the shift of DNA methylome in sperm opposite to the shift associated with physiological aging - sperm DNA methylome rejuvenation, and mild changes in sperm parameters. These results demonstrate for the first time that the balance of mTOR complexes in Sertoli cells regulates the rate of sperm epigenetic aging. Thus, mTOR pathway in Sertoli cells may be used as a novel target of therapeutic interventions to rejuvenate the sperm epigenome in advanced-age fathers. Ethics statementAll procedures followed the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the approval for this study was received from the Institutional Animal Care and Use Committee at University of Massachusetts, Amherst.

developmental biology↗

bioRxiv2022

Reliable estimation of tree branch lengths using deep neural networks

A phylogenetic tree represents hypothesized evolutionary history for a set of taxa. Besides the branching patterns (i.e., tree topology), phylogenies contain information about the evolutionary distances (i.e. branch lengths) between all taxa in the tree, which include extant taxa (external nodes) and their last common ancestors (internal nodes). During phylogenetic tree inference, the branch lengths are typically co-estimated along with other phylogenetic parameters during tree topology space exploration. There are well-known regions of the branch length parameter space where accurate estimation of phylogenetic trees is especially difficult. Several novel studies have recently demonstrated that machine learning approaches have the potential to help solve phylogenetic problems with greater accuracy and computational efficiency. In this study, as a proof of concept, we sought to explore the possibility of machine learning models to predict branch lengths. To that end, we designed several deep learning frameworks to estimate branch lengths on fixed tree topologies from multiple sequence alignments or its representations. Our results show that deep learning methods can exhibit superior performance in some difficult regions of branch length parameter space. For example, in contrast to maximum likelihood inference, which is typically used for estimating branch lengths, deep learning methods are more efficient and accurate when inferring long branches that are associated with distantly related taxa and perform well in the aforementioned challenging regions of the parameter space. Together, our findings represent a next step toward accurate, fast, and reliable phylogenetic inference with machine learning approaches.

evolutionary biology↗

bioRxiv2022

Secondary reversion to sexual monomorphism associated with tissue-specific loss of doublesex expression

Animal evolution is characterized by frequent turnover of sexually dimorphic traits - new sex- specific characters are gained, and some ancestral sex-specific characters are lost, in many lineages. In insects, sexual differentiation is predominantly cell-autonomous and depends on the expression of the doublesex (dsx) transcription factor. In most cases, cells that transcribe dsx have the potential to undergo sex-specific differentiation, while those that lack dsx expression do not. Consistent with this mode of development, comparative research has shown that the origin of new sex-specific traits can be associated with the origin of new spatial domains of dsx expression. In this report, we examine the opposite situation - a secondary loss of the sex comb, a male-specific grasping structure that develops on the front legs of some drosophilid species. We show that, while the origin of the sex comb is linked to an evolutionary gain of dsx expression in the leg, sex comb loss in a newly identified species of Lordiphosa (Drosophilidae) is associated with a secondary loss of dsx expression. We discuss how the developmental control of sexual dimorphism affects the mechanisms by which sex-specific traits can evolve.

evolutionary biology↗

bioRxiv2021

The evolutionary trajectory of drosophilid walking

Neural circuits must both execute the behavioral repertoire of individuals and account for behavioral variation across species. Understanding how this variation emerges over evolutionary time requires large-scale phylogenetic comparisons of behavioral repertoires. Here, we describe the evolution of walking in fruit flies by capturing high-resolution, unconstrained movement from 13 species and 15 strains of drosophilids. We find that walking can be captured in a universal behavior space, the structure of which is evolutionarily conserved. However, the occurrence of, and transitions between, specific movements have evolved rapidly, resulting in repeated convergent evolution in the temporal structure of locomotion. Moreover, a meta-analysis demonstrates that many behaviors evolve more rapidly than other traits. Thus, the architecture and physiology of locomotor circuits can both execute precise individual movements in one species and simultaneously support rapid evolutionary changes in the temporal ordering of these modular elements across clades.

animal behavior and cognition↗

bioRxiv2020

Widespread introgression across a phylogeny of 155 Drosophila genomes

Genome-scale sequence data have invigorated the study of hybridization and introgression, particularly in animals. However, outside of a few notable cases, we lack systematic tests for introgression at a larger phylogenetic scale across entire clades. Here we leverage 155 genome assemblies, from 149 species, to generate a fossil-calibrated phylogeny and conduct multilocus tests for introgression across nine monophyletic radiations within the genus Drosophila. Using complementary phylogenomic approaches, we identify widespread introgression across the evolutionary history of Drosophila. Mapping gene-tree discordance onto the phylogeny revealed that both ancient and recent introgression has occurred across most of the nine clades that we examined. Our results provide the first evidence of introgression occurring across the evolutionary history of Drosophila and highlight the need to continue to study the evolutionary consequences of hybridization and introgression in this genus and across the Tree of Life.

evolutionary biology↗

bioRxiv2020

Deep ancestral introgression shapes evolutionary history of dragonflies and damselflies

Introgression is arguably one of the most important biological processes in the evolution of groups of related species, affecting at least 10% of the extant species in the animal kingdom. Introgression reduces genetic divergence between species, and in some cases can be highly beneficial, facilitating rapid adaptation to ever-changing environmental pressures. Introgression also significantly impacts inference of phylogenetic species relationships where a strictly binary tree model cannot adequately explain reticulate net-like species relationships. Here we use phylogenomic approaches to understand patterns of introgression along the evolutionary history of a unique, non-model insect system: dragonflies and damselflies (Odonata). We demonstrate that introgression is a pervasive evolutionary force across various taxonomic levels within Odonata. In particular, we show that the morphologically "intermediate" species of Anisozygoptera (one of the three primary suborders within Odonata besides Zygoptera and Anisoptera), which retain phenotypic characteristics of the other two suborders, experienced high levels of introgression likely coming from zygopteran genomes. Additionally, we found evidence for multiple cases of deep inter-superfamilial ancestral introgression.

evolutionary biology↗

bioRxiv2019

Accurate inference of tree topologies from multiple sequence alignments using deep learning

Reconstructing the phylogenetic relationships between species is one of the most formidable tasks in evolutionary biology. Multiple methods exist to reconstruct phylogenetic trees, each with their own strengths and weaknesses. Both simulation and empirical studies have identified several "zones" of parameter space where accuracy of some methods can plummet, even for four-taxon trees. Further, some methods can have undesirable statistical properties such as statistical inconsistency and/or the tendency to be positively misleading (i.e. assert strong support for the incorrect tree topology). Recently, deep learning techniques have made inroads on a number of both new and longstanding problems in biological research. Here we designed a deep convolutional neural network (CNN) to infer quartet topologies from multiple sequence alignments. This CNN can readily be trained to make inferences using both gapped and ungapped data. We show that our approach is highly accurate, often outperforming traditional methods, and is remarkably robust to bias-inducing regions of parameter space such as the Felsenstein zone and the Farris zone. We also demonstrate that the confidence scores produced by our CNN can more accurately assess support for the chosen topology than bootstrap and posterior probability scores from traditional methods. While numerous practical challenges remain, these findings suggest that deep learning approaches such as ours have the potential to produce more accurate phylogenetic inferences.

evolutionary biology↗

bioRxiv2017

Firefly genomes illuminate the origin and evolution of bioluminescence

Fireflies are among the best-studied of the bioluminescent organisms. Despite longterm interest in the biochemistry, neurobiology, and evolution of firefly flash signals and the widespread biotechnological applications of firefly luciferase, only a limited set of genes related to this complex trait have been described. To investigate the genetic basis of firefly bioluminescence, we generated a high-quality reference genome for the Big Dipper firefly Photinus pyralis, from which the first laboratory luciferase was cloned, using long-read (PacBio), short-read (Illumina), and Hi-C sequencing technologies. To facilitate comparative genomics, we also generated short-read genome assemblies for a Japanese firefly Aquatica lateralis and a bioluminescent click beetle, Ignelater luminosus. Analyses of these genomic datasets supports at least two independent gains of luminescence in beetles, and provides new insights into the evolution of beetle bioluminescence and chemical defenses that likely co-evolved over their 100 million years of evolution.

genomics↗