Biology subjects

Sackton, T. B.

Publications and source records attributed to Sackton, T. B..

At least 19 recordsLinked to original sources

bioRxiv2026

Independent evolution of harmala alkaloids in medicinal Syrian rue and ayahuasca plants

Plants from distantly related lineages can produce identical neuroactive molecules, many of which have been independently adopted across human societies for their medicinal and cognition-altering effects. This phenomenon is exemplified by the traditional use of Syrian rue (Peganum harmala) and the ayahuasca vine (Banisteriopsis caapi) for medicine and ritual. Despite diverging over 100 million years ago and inhabiting different continents and climates, both plants synthesize harmala alkaloids (HAs), which inhibit human monoamine oxidase and exhibit diverse neuroactive effects. Here, we combine gene expression analyses, genomics, and enzyme characterization to elucidate HA biosynthesis for both Syrian rue and ayahuasca vine. We reveal multiple layers of biochemical and genetic convergence in these pathways, including independent duplication and neofunctionalization of an ancestral enzyme from serotonin biosynthesis, and lineage-specific repurposing of primary metabolic genes to generate a reactive precursor for alkaloid scaffold formation. Our study resolves biosynthetic routes to HAs in two medicinal plants and demonstrates convergent evolution of specialized metabolism at the levels of enzymes, pathways, and genomes.

biochemistry↗

bioRxiv2026

Unmasking the large and highly repetitive genome of Phlox reveals a complex evolutionary history of speciation with gene flow

The large size and high repetitive content of many plant genomes have hindered elucidation of how the fundamental processes of evolution give rise to speciation. Here we present chromosome-level assemblies of 6 gigabase genomes for four closely related Phlox wildflower species. We generate extensive population genetic data for the three well-studied annual species P. drummondii, P. cuspidata, and P. roemeriana, including structural variation from whole-genome long-read resequencing data. The whole-genome assemblies reveal extensive differences in amount and distribution of genetic variation within and between species, reflective of differences in life-history strategies, mating systems, and edaphic specialization. The population genetic data exposes a history of widespread and consistent gene flow between all three annual Phlox species throughout their divergence and speciation. Our unmasking of structural variants and repetitive elements exposes rich and dynamic forms of genetic variation that show strong phylogenetic signal and pervasive patterns of gene flow. Our results lay a foundation for untangling the highly complex genomes of plants to make advancements in our understanding of the processes of speciation and divergence.

evolutionary biology↗

bioRxiv2025

Genomic resources for comparative analyses of obligate avian brood parasitism

Examples of convergent evolution, wherein distantly related organisms evolve similar traits, including behaviors, underscore the adaptive power of natural selection. In birds, obligate brood parasitism, and the associated loss of parental care behaviors, has evolved independently in seven different lineages, though little is known about the genetic basis of the complex suite of traits associated with this rare life history strategy. We generated genome assemblies for ten brood parasitic species plus eight species representatives of their parental/nesting outgroups. This includes nine long-read chromosome-level assemblies, with scaffold N50 sizes ranging from 38.1 to 72.6 MB, and gene representation completeness measures >97%. Leveraging this new catalog of avian genomes, we constructed clade-level alignments that reveal variation in chromosomal synteny, provide first-time or improved annotations of protein-coding and non-coding genes, and define cross-species ortholog reference sets. We also refine estimates for the timing of the seven independent origins of brood parasitism, ranging from recent events such as 1.6 to 4.5 million years ago in Molothrus cowbirds to much earlier origins over 30 million years ago in two of the three cuckoo lineages. These genomic resources lay the foundation for investigating the genetic and genomic underpinnings of brood parasitism, including the loss of parental care, shifts in mating systems, perhaps resulting in heightened sperm competition, elevated annual fecundity, improved spatial cognition related to nest-finding, and the diverse adaptations shaped by intense coevolution with host species.

genomics↗

bioRxiv2025

Combining population genomics with ancient DNA to understand island colonization history of the Madagascar turtle dove

The Mascarene archipelago (Mauritius, Reunion and Rodrigues), characterized by first human arrival being recent, offers a unique setting to study species colonization. Here we use a combination of modern and ancient DNA data as a case study to investigate the recent colonization history of a species of concern in relation to conservation programs - the Madagascar turtle dove (Nesoenas picturata) on Mauritius and Reunion. We generated a reference genome and re-sequenced genomes from contemporary N. picturata populations, as well as genome-wide data from relevant subfossils. A combination of model-free inferences, site frequency spectrum (SFS) based demographic modelling, and analyses of population structure including that of subfossils indicate that N. picturata colonized both islands independently and naturally from Madagascar, long before human arrival. Summary statistics and SFS-based modeling reveal large effective population sizes (Ne) and high genetic diversity in island populations, conflicting with historical accounts of human-induced demographic collapse. Based on goodness-of-fit, genetic structure and diversity indices do not discriminate between two solutions, one of which posits large recent Ne and negligible translocation rates, while the other supports recent severe bottlenecks followed by high post-human translocation from Madagascar. Nonetheless, linkage disequilibrium provides stronger evidence for the latter scenario, which may also explain high genetic diversity. Both modern and ancient DNA data sources independently support the classification of N. picturata as native to both islands. Our findings highlight the importance of validating demographic models with multiple summary statistics, and potential of using a combination of different data sources to resolve colonization history in recent time.

evolutionary biology↗

bioRxiv2025

Efficient Estimation of Nucleotide Diversity and Divergence using Depth Information

The increasing scale of population genomic datasets presents computational challenges in estimating summary statistics such as nucleotide diversity ({pi}) and divergence (dxy). Unbiased estimates of diversity require knowledge of missing data and existing tools require all-sites VCFs. However, generating these files is computationally expensive for large datasets. Here, we introduce Callable Loci And More (clam), a tool that leverages callable loci--determined from depth information--to estimate population genetic statistics using a variant-only VCF. This approach offers improvements in storage footprint and computational performance compared to contemporary methods. We benchmark clam using a large muskox dataset and demonstrate that it produces unbiased estimates of {pi} while reducing runtime and storage requirements, compared to an existing approach. clam provides an efficient and scalable alternative for population genomic analyses, facilitating the study of increasingly large and diverse datasets. clam is available as a standalone program and integrated into snpArcher for efficient reproducible population genomic analysis.

genomics↗

bioRxiv2025

Comparative population genomics reveals convergent adaptation across independent origins of avian obligate brood parasitism

Parental care evolved as a strategy to enhance offspring survival at the cost of reduced fecundity. While most birds provide parental care, obligate brood parasites circumvent this tradeoff by exploiting the parental behavior of other species. This radical life history shift has occurred independently seven times in birds, offering an outstanding opportunity to test for convergent patterns of adaptation in the genome. To investigate genomic adaptations underlying this transition, we analyzed population resequencing data from five brood-parasitic species across three independent origins of brood parasitism -- three parasitic finches (family Viduidae), a honeyguide, and a cowbird -- alongside related non-parasitic (parental) outgroups. Using the McDonald-Kreitman framework, we found evidence for repeated adaptation in genes involved in spermatogenesis and sperm function in multiple parasitic clades, but not in the matched outgroup parental species. This is consistent with evidence for increased male-male competition in parasitic lineages as a result of the loss of parental care. In addition, we detected selective sweeps near genes associated with nervous system development in parasitic lineages, perhaps associated with improved spatial cognition that aids brood parasites in locating, monitoring, and laying eggs in host nests. Finally, we found more selective sweeps in host-specific brood parasites as compared to parental outgroups, perhaps reflecting ongoing host-parasite coevolutionary arms races.

evolutionary biology↗

bioRxiv2025

Comparative population pangenomes reveal unexpected complexity and fitness effects of structural variants

Structural variants (SVs) are widespread in vertebrate genomes, yet their evolutionary dynamics remain poorly understood. Using 45 long-read de novo genome assemblies and pangenome tools, we analyze SVs within three closely related species of North American jays (Aphelocoma, scrub-jays) displaying a 60-fold range in effective population size. We find rapid evolution of genome architecture, including [~]100 Mb variation in genome size driven by dynamic satellite landscapes with unexpectedly long (> 10 kb) repeat units and widespread variation in gene content, influencing gene expression. SVs exhibit slightly deleterious dynamics modulated by variant length and population size, with strong evidence of adaptive fixation only in large populations. Our results demonstrate how population size shapes the distribution of SVs and the importance of pangenomes to characterizing genomic diversity.

evolutionary biology↗

bioRxiv2024

Minus the Error: Estimating dN/dS and Testing for Natural Selection in the Presence of Residual Alignment Errors

Positive selection is an evolutionary process which increases the frequency of advantageous mutations because they confer a fitness benefit. Inferring the past action of positive selection on protein-coding sequences is fundamental for deciphering phenotypic diversity and the emergence of novel traits. With the advent of genome-wide comparative genomic datasets, researchers can analyze selection not only at the level of individual genes but also globally, delivering systems-level insights into evolutionary dynamics. However, genome-scale datasets are generated with automated pipelines and imperfect curation that does not eliminate all sequencing, annotation, and alignment errors. Positive selection inference methods are highly sensitive to such errors. We present BUSTED-E: a method designed to detect positive selection for amino acid diversification while concurrently identifying some alignment errors. This method builds on the flexible branch-site random effects model (BUSTED) for fitting distributions of dN/dS, with a critical modification: it incorporates an "error-sink" component to represent an abiological evolutionary regime. Using several genome-scale biological datasets that were extensively filtered using state-of-the art automated alignment tools, we show that BUSTED-E identifies pervasive residual alignment errors, produces more realistic estimates of positive selection, reduces bias, and improves biological interpretation. The BUSTED-E model promises to be a more stringent filter to identify positive selection in genome-wide contexts, thus enabling further characterization and validation of the most biologically relevant cases.

evolutionary biology↗

bioRxiv2024

Convergent and lineage-specific genomic changes contribute to adaptations in sugar-consuming birds

High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation, lipid, amino acid and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL, a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL, highlighting its adaptive role in high-sugar diets. Summary Figure: Our comparative screens across four independent sugar-feeding bird groups identified both repeated and lineage-specific targets of selection O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/610474v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@148f5c8org.highwire.dtl.DTLVardef@1005dbaorg.highwire.dtl.DTLVardef@1097facorg.highwire.dtl.DTLVardef@9d365c_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2024

Convergent evolution of noncoding elements associated with short tarsus length in birds

Convergent evolution is the independent evolution of similar traits in unrelated lineages across the Tree of Life. Various factors underlie convergent evolution including convergent rate changes through consistent shifts in substitution rate in the same genes or gene networks. In this study, we use comprehensive phenotypic data to identify seven bird clades with independent shortening in tarsus length and use both comparative genomic and population genetic data to identify convergent evolutionary changes among four target clades with shifts to shorter optimal tarsus length. Using a newly generated, comprehensive set of avian conserved non-exonic elements (CNEEs), we find strong evidence for convergent acceleration in short-tarsi clades among CNEEs, but not protein-coding genes. Accelerated CNEEs in short-tarsi clades are preferentially located near genes with functions in development, with the strongest enrichment associated with skeletal system development. Further analysis of gene networks highlighted this larger role of changes in regulation of broadly homologous developmental genes and pathways as being an integral aspect of limb size variability in birds.

genomics↗

bioRxiv2024

Building better genome annotations across the tree of life

Recent technological advances in long read DNA sequencing accompanied by dramatic reduction in costs have made the production of genome assemblies financially achievable and computationally feasible, such that genome assembly no longer represents the major hurdle to evolutionary analysis for most non-model organisms. Now, the more difficult challenge is to properly annotate a draft genome assembly once it has been constructed. The primary challenge to annotations is how to select from the myriad gene prediction tools that are currently available, determine what kinds of data are necessary to generate high quality annotations, and evaluate the quality of the annotation. To determine which methods perform the best and determine whether the inclusion of RNA-seq data is necessary to obtain a high-quality annotation, we generated annotations with 10 different methods for 21 different species spanning vertebrates, plants, and insects. We found that the RNA-seq assembler Stringtie and the annotation transfer method TOGA were consistently top performers across a variety of metrics including BUSCO recovery, CDS length, and false positive rate, with the exception that TOGA performed less in plants with larger genomes. RNA-seq alignment rate was best with RNA-seq assemblers. HMM-based methods such as BRAKER, MAKER, and multi-genome AUGUSTUS mostly underperformed relative to Stringtie and TOGA. In general, inclusion of RNA-seq data will lead to substantial improvements to genome annotations, and there may be cases where complementarity among methods may motivate combining annotations from multiple sources.

bioinformatics↗

bioRxiv2023

A phylogenetic method linking nucleotide substitution rates to rates of continuous trait evolution

Genomes contain conserved non-coding sequences that perform important biological functions, such as gene regulation. We present a phylogenetic method, PhyloAcc-C, that associates nucleotide substitution rates with changes in a continuous trait of interest. The method takes as input a multiple sequence alignment of conserved elements, continuous trait data observed in extant species, and a background phylogeny and substitution process. Gibbs sampling is used to assign rate categories (background, conserved, accelerated) to lineages and explore whether the assigned rate categories are associated with increases or decreases in the rate of trait evolution. We test our method using simulations and then illustrate its application using mammalian body size and lifespan data previously analyzed with respect to protein coding genes. Like other studies, we find processes such as tumor suppression, telomere maintenance, and p53 regulation to be related to changes in longevity and body size. In addition, we also find that skeletal genes, and developmental processes, such as sprouting angiogenesis, are relevant. The R/C++ software package implementing our method is available under an open source license from https://github.com/phyloacc/PhyloAcc-C.

bioinformatics↗

bioRxiv2023

A fast, reproducible, high-throughput variant calling workflow for evolutionary, ecological, and conservation genomics

The increasing availability of genomic resequencing datasets and high quality reference genomes across the tree of life present exciting opportunities for comparative population genomic studies. However, substantial challenges prevent the simple reuse of data across different studies and species, arising from variability in variant calling pipelines, data quality, and the need for computationally intensive reanalysis. Here, we present snpArcher, a flexible and highly efficient workflow designed for the analysis of genomic resequencing data in non-model organisms. snpArcher provides a standardized variant calling pipeline and includes modules for variant quality control, data visualization, variant filtering, and other downstream analysis.Implemented in Snakemake, snpArcher is user-friendly, reproducible, and designed to be compatible with HPC clusters and cloud environments. To demonstrate the flexibility of this pipeline, we applied snpArcher to 26 public resequencing datasets from non-mammalian vertebrates. These variant datasets are hosted publicly to enable future comparative population genomic analyses. With its extensibility and the availability of public datasets, snpArcher will contribute to a broader understanding of genetic variation across species by facilitating rapid use and reuse of large genomic datasets.

genomics↗

bioRxiv2023

Widespread but spotty: Atlantic cod is a complex of five species through ecological speciation.

Withdrawal StatementThe authors have withdrawn their manuscript because they have discovered errors in the alignment of parts of the data. Miscommunication with the sequencing center led to a misunderstanding of the pooling design and incorrect merging of sequencing read files from different individuals into single bam files. Thus bam alignments for each individual sample of four out of 12 batches are based on a majority of reads from that individual but also on reads from one or two other individuals. Individuals in eight other batches were not affected by this. However, for this paper, the entire data was jointly genotyped to produce vcf files, and the joint genotyping may thus indirectly affect samples of other batches. Revising the paper by teasing apart the affected and non-affected parts of the data is not an option, and they, therefore, withdraw the preprint. They are reanalyzing the dataset. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

evolutionary biology↗

bioRxiv2022

PhyloAcc-GT: A Bayesian method for inferringpatterns of substitution rate shifts and associations with binary traits under gene tree discordance

An important goal of evolutionary genomics is to identify genomic regions whose substitution rates differ among lineages. For example, genomic regions experiencing accelerated molecular evolution in some lineages may provide insight into links between genotype to phenotype. Several comparative genomics methods have been developed to identify genomic accelerations between species, including a Bayesian method called PhyloAcc, which models shifts in substitution rate in multiple target lineages on a phylogeny. However, few methods consider the possibility of discordance between the trees of individual loci and the species tree due to incomplete lineage sorting, which might cause false positives. Here we present PhyloAcc-GT, which extends PhyloAcc by modeling gene tree heterogeneity to detect rate shifts across genomic regions. Given a species tree, we adopt the multispecies coalescent model as the prior distribution of gene trees, use Markov chain Monte Carlo (MCMC) for inference, and design novel MCMC moves to sample gene trees efficiently. Through extensive simulations, we show that PhyloAcc-GT outperforms PhyloAcc and other methods in identifying target-lineage-specific accelerations and detecting complex patterns of rate shifts, and is robust to specification of population size parameters. We apply PhyloAcc-GT to two examples of convergent evolution: flightlessness in ratites and marine mammal adaptations. PhyloAcc-GT is usually more conservative than PhyloAcc in calling convergent rate shifts because it identifies more accelerations on ancestral than on terminal branches. In summary, PhyloAcc-GT is a useful tool to identify shifts in substitution rate associated with specific target lineages while accounting for incomplete lineage sorting.

evolutionary biology↗

bioRxiv2022

Patterns of lineage-specific genome evolution in the brood parasitic black-headed duck (Heteronetta atricapilla)

Occurring independently at seven separate origins across the avian tree of life, obligate brood parasitism is a unique suite of traits observed in only approximately 1% of all bird species. Obligate brood parasites exhibit varied physiological, morphological, and behavioural traits across lineages, but common among all obligate brood parasites is that the females lay their eggs in the nest of other species. Unique among these species is the black-headed duck (Heteronetta atricapilla), a generalist brood parasite that is the only obligate brood parasite among waterfowl. This provides an opportunity to assess evolutionary changes in traits associated with brood parasitism, notably the loss of parental care behaviours, with an unspecialized brood parasite. We generated new high-quality genome assemblies and genome annotations of the black-headed duck and three related non-parasitic species (freckled duck, African pygmy-goose, and ruddy duck). With these assemblies and existing public genome assemblies, we produced a whole genome alignment across Galloanserae to identify conserved non-coding regions with atypical accelerations in the black-headed duck and coding genes with evidence of positive selection, as well as to resolve uncertainties in the duck phylogeny. To complement these data, we sequenced a population sample of black-headed ducks, allowing us to conduct McDonald-Kreitman tests of lineage-specific selection. We resolve the existing polytomy between our focal taxa with concordance from coding and non-coding sequences, and we observe stronger signals of evolution in non-coding regions of the genome than in coding regions. Collectively, the new high-quality genomes, comparative genome alignment, and population genomics provide a detailed picture of genome evolution in the only brood parasitic duck.

evolutionary biology↗

bioRxiv2022

Interpreting the pervasive observation of U-shaped Site Frequency Spectra

The standard neutral model of molecular evolution has traditionally been used as the null model for population genomics. We gathered a collection of 45 genome-wide site frequency spectra from a diverse set of species, most of which display an excess of low and high frequency variants compared to the expectation of the standard neutral model, resulting in U-shaped spectra. We show that multiple merger coalescent models often provide a better fit to these observations than the standard Kingman coalescent. Hence, in many circumstances these under-utilized models may serve as the more appropriate reference for genomic analyses. We further discuss the underlying evolutionary processes that may result in the widespread U-shape of frequency spectra.

evolutionary biology↗

bioRxiv2020

HieRFIT: Hierarchical Random Forest for Information Transfer

The emergence of single-cell RNA sequencing (scRNA-seq) has led to an explosion in novel methods to study biological variation among individual cells, and to classify cells into functional and biologically meaningful categories. Here, we present a new cell type projection tool, HieRFIT (Hierarchical Random Forest for Information Transfer), based on hierarchical random forests. HieRFIT uses a priori information about cell type relationships to improve classification accuracy, taking as input a hierarchical tree structure representing the class relationships, along with the reference data. We use an ensemble approach combining multiple random forest models, organized in a hierarchical decision tree structure. We show that our hierarchical classification approach improves accuracy and reduces incorrect predictions especially for inter-dataset tasks which reflect real life applications. We use a scoring scheme that adjusts probability distributions for candidate class labels and resolves uncertainties while avoiding the assignment of cells to incorrect types by labeling cells at internal nodes of the hierarchy when necessary. Using HieRFIT, we re-analyzed publicly available scRNA-seq datasets showing its effectiveness in cell type cross-projections with inter/intra-species examples. HieRFIT is implemented as an R package and it is available at (https://github.com/yasinkaymaz/HieRFIT/releases/tag/v1.0.0)

bioinformatics↗