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Interpretable and predictive models to harness the life science data revolution

The proliferation of high-dimensional data in ecology and evolutionary biology raises the promise of statistical and machine learning models that are highly predictive and interpretable. However, high-dimensional data are commonly burdened with an inherent trade-off: in-sample prediction of outcomes will improve as additional variables are included in the model, but this may come at the cost of poor predictive accuracy and limited generalizability for future or unsampled observations (out-of-sample prediction). To confront this problem of overfitting, sparse models can focus on key variables by correctly placing low weight on unimportant variables. We competed nine methods to quantify their performance in variable selection and prediction using simulated data with different sample sizes, numbers of variables, and strengths of effects. Overfitting was typical for many methods and simulation scenarios. Despite this, in-sample and out-of-sample prediction converged on the true predictive target for simulations with more observations, larger causal effects, and fewer variables. Accurate variable selection to support process-based understanding will be unattainable for many realistic sampling schemes in ecology and evolution. We use our analyses to characterize data attributes for which statistical learning is possible, and illustrate how some sparse methods can achieve predictive accuracy while mitigating and learning the extent of overfitting.

genomics↗

Efficient Gene Editing and Overexpression of Gametophyte Transformation in a Model Fern

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-related nuclease (Cas) system allows precise and easy editing of genes in many plant species. However, this system has not yet been applied to any fern species due to the complex characteristics of fern genomes, genetics and physiology. Here, we established, for the first time, a protocol for gametophyte-based screening single-guide RNAs (sgRNAs) with high efficiency for CRISPR/Cas-mediated gene editing in a model fern species, Ceratopteris richardii. We utilized the C. richardii Actin promoter to drive sgRNA expression and enhanced CaMV 35S promoter to drive the expression of Streptococcus pyogenes Cas9 in this CRISPR-mediated editing system, which was employed to successfully edit a few genes (e.g., nucleotidase/phosphatase 1, CrSAL1; Cryptochrome 4, CRY4) and CrPDS, encoding a phytoene desaturase protein that resulted in an albino phenotype in C. richardii. Knockout of CrSAL1 resulted in significantly reduced stomatal conductance (gs), leaf transpiration rate (E), stomatal/pore length, and abscisic acid (ABA)-induced reactive oxygen species (ROS) accumulation in guard cells. Moreover, CrSAL1 overexpressing plants showed significantly increased net photosynthetic rate (A), gs, E and intrinsic water use efficiency (iWUE) as well as most of the stomatal traits and ROS production in guard cells compared to those in the wild-type (WT) plants. Taken together, the optimized CRISPR/Cas9 system provides a useful tool for functional genomics in a model fern species, allowing the exploration of fern gene functions for evolutionary biology, herbal medicine discovery and agricultural applications.

plant biology↗

Diverging Arabidopsis populations quickly accumulate pollen-acting genetic incompatibilities

The process by which species diverge from one another, gradually accumulate genetic incompatibilities and eventually reach full-fledged reproductive isolation is a key question in evolutionary biology. However, the nature of reproductive barriers, the pace at which they accumulate and their genomic distribution remain poorly documented. The disruption of co-adapted epistatic interactions in hybrids and the accumulation of selfish genetic elements are proposed contributors to this process, and can lead to the distortion of the mendelian segregation of the affected loci across the genome. In this study we detect and quantify segregation distortion across the genomes of crosses produced from a diverse sampling of Arabidopsis lyrata and A. halleri populations, two species at the early stages of speciation and that can still interbreed. We show that both the frequency of occurrence and the magnitude of distortion loci increase as the parents genetic distance from one another increases. We also observe that distorter loci evolve rapidly, as they occur not only within interspecific hybrids, but also in intraspecific hybrids produced from isolated population crosses. Finally, we identify both genome-wide non-independence and two specific genomic regions on different chromosomes where opposite distortion effects are repeatedly observed across multiple F1 individuals, suggesting negative epistasis is a major contributor to the evolution of hybrid segregation distortion. Our study demonstrates that pollen-acting segregation distortion is ubiquitous, and contributes not only to the ongoing reproductive isolation between A. halleri and A. lyrata, but also between very recently diverged populations of the same species.

genomics↗

A High-quality Oxford Nanopore Assembly of the Hourglass Dolphin (Sagmatias cruciger) Genome

The hourglass dolphin (Lagenorhynchus cruciger) is a small cetacean species of the Southern Ocean, with significance to iwi M[a]ori (M[a]ori tribes) of Aotearoa New Zealand as taonga (treasured/valued). Due to the remoteness and difficulty of surveying Antarctic waters, it remains one of the least-studied dolphin species. A recent stranding of an hourglass dolphin represented a rare opportunity to generate a genome assembly as a resource for future study into the conservation and evolutionary biology of this species. In this study, we present a high-quality genome assembly of an hourglass dolphin individual using a single sequencing platform, Oxford Nanopore Technologies, coupled with computationally efficient assembly methods. Our assembly strategy yielded a genome of high contiguity (N50 of 8.07 Mbp) and quality (98.3% BUSCO completeness). Compared to other Delphinoidea reference genomes, this assembly has fewer missing BUSCOs than any except Orcinus orca, more single-copy complete BUSCOs than any except Phocoena sinus, and 20% fewer duplicated BUSCOs than the average Delphinoidea reference genome. This suggests that it is one of the most complete and accurate marine mammal genomes to date. This study showcases the feasibility of a cost-effective mammalian genome assembly method, allowing for genomic data generation outside the traditional confines of academia and/or resource-rich genome assembly hubs, and facilitating the ability to uphold Indigenous data sovereignty. In the future the genome assembly presented here will allow valuable insights into the past population size changes, adaptation, vulnerability to future climate change of the hourglass dolphin and related species.

genomics↗

Identification of 5mC within heterogenous tissue using de-novo somatic mutations

Tissues represent a fundamental evolutionary interface at the junction of genotype and phenotype. Indeed, gene regulation often occurs at the tissue level and manifests itself through tissue-specific epigenetic modifications. Studies investigating tissue epigenetics are limited by access to pure tissues. Tissues not only differ epigenetically, they are also subject to genetic differentiation through somatic mutations. As somatic mutations follow predictable patterns of inheritance, the application of population genomic approaches to inter- and intra-tissue variation could allow for the efficient detection of epigenetic modifications, even when tissue samples are convoluted. Here, we present an approach that uses de-novo somatic mutations to deconvolute 5mC methylation patterns through analysis of shifts in tissue-specific allele frequencies. We use simulations and bisulfite sequencing data to show that somatic mutations are common and detectable in next-generation sequencing data. We then use changes in mutation frequencies to accurately derive the proportional tissue of origin along a gradient of in silico subsamples of mixed-tissue bisulfite reads. We confirm that mixed tissues bias estimates of methylation levels and prevent detection of methylation differences at high levels of mixture. Our derived estimates of tissue contamination allow for unbiased and accurate deconvolution of mixed-tissue methylations in CpG and non-CpG context. We are ultimately able to recover 15-30% of differentially-methylated sites, and approximately 40-90% of differentially-methylated CpG islands and gene bodies in any cytosine context at contamination levels up to 90%. Our findings highlight the utility of population genomic approaches across scales, and expand the accessibility of epigenetics studies within evolutionary biology.

genomics↗

A latitudinal gradient of reference genomes

Global inequality rooted in legacies of colonialism and uneven development can lead to systematic biases in scientific knowledge. In ecology and evolutionary biology, findings, funding and research effort are disproportionately concentrated at high latitudes while biological diversity is concentrated at low latitudes. This discrepancy may have a particular influence in fields like phylogeography, molecular ecology and conservation genetics, where the rise of genomics has increased the cost and technical expertise required to apply state-of-the-art methods. Here we ask whether a fundamental biogeographic pattern--the latitudinal gradient of species richness in tetrapods--is reflected in available reference genomes, an important data resource for various applications of molecular tools for biodiversity research and conservation. We also ask whether sequencing approaches differ between the Global South and Global North, reviewing the last five years of conservation genetics research in four leading journals. We find that extant reference genomes are scarce relative to species richness at low latitudes, and that reduced-representation and whole-genome sequencing are disproportionately applied to taxa in the Global North. We conclude with recommendations to close this gap and improve international collaborations in biodiversity genomics.

genomics↗

Predicting bacterial phenotypic traits through improved machine learning using high-quality, curated datasets

Predicting prokaryotic phenotypes - observable traits that govern functionality, adaptability, and interactions - holds significant potential for fields such as biotechnology, environmental sciences, and evolutionary biology. This study leverages machine learning to explore the relationship between prokaryotic genotypes and phenotypes. Taking advantage of the highly standardized datasets in the BacDive database, we modeled eight physiological properties based on protein family inventories, discuss the evaluation metrics, and explore the biological implications of our models. The high confidence values of our predictions highlight the importance of data quality and quantity for a reliable inference of bacterial phenotypes. Our approach yielded nearly 55,000 new data points for approximately 20,000 strains which are published openly in the BacDive database, enriching existing phenotypic datasets and paving the way for future research and analysis. The open-source software generated can readily be applied to other datasets, for example the IMG/M system for metagenomics, as well as different applications, like the assessment of the potential of soil bacteria for bioremediation projects.

bioinformatics↗

Miniaturizing, Modifying, and Augmenting Nature's Proteins with Raygun

Proteins have evolved over billions of years through extensive and coordinated substitutions, insertions and deletions (indels). Computational protein design cannot yet fully mimic natures ability to engineer new proteins from existing templates. Protein language models generate informative per-residue representations, but leveraging them to execute large-scale, function-preserving mutations and indels has remained beyond reach. We introduce Raygun, a generative AI framework that unlocks efficient miniaturization, modification, and augmentation of proteins, using a novel probabilistic encoding of protein sequences constructed from language model embeddings. Emulating evolution, Raygun shrinks proteins by 10-25% (sometimes over 50%) while preserving predicted structural integrity and fidelity, introduces extensive sequence diversity while preserving functional sites, and can expand proteins beyond their natural size. These capabilities unlock new opportunities in gene therapy and biotechnology. In cell-based validation, Raygun successfully miniaturized fluorescent proteins, two of which are smaller than 96% of fluorescent proteins reported in FPbase, as well as TurboID, a synthetic biotin ligase widely adopted for proteomics. It also successfully expanded Epidermal Growth Factor (EGF), a natural binding partner to the EGFR protein, generating EGF variants with higher binding affinity than the wildtype. Rayguns conceptual innovations in template-based protein design reveal that protein function can be encoded in a length-independent space. This fundamental insight bridges protein representation learning with evolutionary biology and could unlock the development of more efficient molecular tools and biological therapeutics.

bioinformatics↗

The dynamics of Staphylococcal infection and their treatment with antibiotics and bacteriophage in the Galleria mellonella model system

Critical to our understanding of infections and their treatment is the role the innate immune system plays in controlling bacterial pathogens. Nevertheless, many in vivo systems are made or modified such that they do not have an innate immune response. Use of these systems denies the opportunity to examine the synergy between the immune system and antimicrobial agents. In this study we demonstrate that the larva of Galleria mellonella is an effective in vivo model for the study of the population and evolutionary biology of bacterial infections and their treatment. To do this we test three hypotheses concerning the role of the innate immune system during infection. We show: i) sufficiently high densities of bacteria are capable of saturating the innate immune system, ii) bacteriostatic drugs and bacteriophages are as effective as bactericidal antibiotics in preventing mortality and controlling bacterial densities, and iii) minority populations of bacteria resistant to a treating antibiotic will not ascend. Using a highly virulent strain of Staphylococcus aureus and a mathematical computer-simulation model, we further explore how the dynamics of the infection within the short term determine the ultimate infection outcome. We find that immune activation in response to high densities of bacteria leads to a strong but short-lived immune response which ultimately results in a high degree of mortality. Overall, our findings illustrate the utility of the G. mellonella model system in conjunction with established in vivo models in studying infectious disease progression and treatment. Significance statementCentral to our understanding of the course of bacterial infections and their treatment is the contribution of the innate immune system. We use the larvae of Galleria mellonella to test hypothesis about the role of the innate immune system on Staphylococcus aureus infections. We demonstrate that the innate immune system of these larvae can control the infection and be saturated by high bacterial densities. As a consequence of this innate immune system, bacteriostatic drugs and phages are as effective as bactericidal drugs, and minority populations of bacteria resistant to antibiotics do not ascend. Our findings illustrate the utility of G. mellonella as a model for studying infections dynamics and therapeutic strategies.

microbiology↗

Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes

A major goal in evolutionary biology and biomedicine is to understand the complex interactions between genetic variants, the epigenome, and gene expression. However, the causal relationships between these factors remain poorly understood. mSTARR-seq, a methylation-sensitive massively parallel reporter assay, is capable of identifying methylation-dependent regulatory activity at many thousands of genomic regions simultaneously, and allows for the testing of causal relationships between DNA methylation and gene expression on a region-by-region basis. Here, we developed a multiplexed mSTARR-seq protocol to assay naturally occurring human genetic variation from 25 individuals sampled from 10 localities in Europe and Africa. We identified 6,957 regulatory elements in either the unmethylated or methylated state, and this set was enriched for enhancer and promoter annotations, as expected. The expression of 58% of these regulatory elements was modulated by methylation, which was generally associated with decreased RNA expression. Within our set of regulatory elements, we used allele-specific expression analyses to identify 8,020 sites with genetic effects on gene regulation; further, we found that 42.3% of these genetic effects varied between methylated and unmethylated states. Sites exhibiting methylation-dependent genetic effects were enriched for GWAS and EWAS annotations, implicating them in human disease. Compared to datasets that assay DNA from a single European individual, our multiplexed assay uncovers dramatically more genetic effects and methylation-dependent genetic effects, highlighting the importance of including diverse individuals in assays which aim to understand gene regulatory processes.

genomics↗

GageTracker: a tool for dating gene age by micro- and macro-synteny with high speed and accuracy

With the advent of the Earth Genome Project, an increasing number of species' genomes presents exciting opportunities for exploring genetic and phenotypic diversity in organisms. Determining the origin time of genes facilitates the elucidation of crucial genetic mechanisms underlying significant biological evolutionary questions such as the transition from aquatic to terrestrial life, the emergence of mammals, the origin of humans, as well as the development of species- or lineage-specific traits. However, accurately determining the origin time of these genes in species separated by long evolutionary distances remains a major challenge in bioinformatics as these genes often undergo significant changes in their genome sequences, making it difficult to trace them back to their origin. Here, we proposed a new approach for dating gene age based on the micro- and macro-synteny algorithms. This approach employs the parallel computation of orthologous genome alignments across multiple species. Our method was integrated into the GageTracker (Gene Age Tracker) software, providing a fast and accurate way to trace gene age with minimal user input, available at https://github.com/RiversDong/GageTracker. Benchmarked against the simMammals dataset (Alignathon), GageTracker achieved the same high-quality genome alignments as the optimized LastZ aligner, but improved operation speed by 1.4-7 times. In a separate analysis of 12 Drosophila genomes, GageTracker efficiently assessed the ages of 23,720 genes (including ~13,965 protein-coding genes) in just ~22 hours with default parameters. When comparing with the GenTree database (recognized as the most comprehensive and accurate tool for evaluating gene age), GageTracker achieved an impressive ~94.4% accuracy and ~99% macro consistency in assessing the age of protein-coding genes. Moreover, for the ~5.6% conflicting genes, GageTracker displayed slightly higher support rates than GenTree, as evidenced by data from OrthoDB, FlyBase, and Ensembl ortholog databases. Notably, younger genes identified by GageTracker exhibited a preferential expression pattern in the testis, further reinforcing the reliability of GageTracker in accurately tracing gene age.

bioinformatics↗

Cost-effective solutions for high-throughput enzymatic DNA methylation sequencing

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, geroscience, and medical genomics. While costs are decreasing, whole-genome DNA methylation profiling remains prohibitively expensive for most population-scale studies, creating a need for cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target a subset of the genome). Most common whole genome and reduced representation techniques rely on bisulfite conversion, which can damage DNA resulting in DNA loss and sequencing biases. Enzymatic methyl sequencing (EM-seq) was recently proposed to overcome these issues, but thorough benchmarking of EM-seq combined with cost-effective, reduced representation strategies has not yet been performed. To do so, we optimized Targeted Methylation Sequencing protocol (TMS)--which profiles [~]4 million CpG sites--for miniaturization, flexibility, and multispecies use at a cost of [~]$80. First, we tested modifications to increase throughput and reduce cost, including increasing multiplexing, decreasing DNA input, and using enzymatic rather than mechanical fragmentation to prepare DNA. Second, we compared our optimized TMS protocol to commonly used techniques, specifically the Infinium MethylationEPIC BeadChip (n=55 paired samples) and whole genome bisulfite sequencing (n=6 paired samples). In both cases, we found strong agreement between technologies (R{superscript 2} = 0.97 and 0.99, respectively). Third, we tested the optimized TMS protocol in three non-human primate species (rhesus macaques, geladas, and capuchins). We captured a high percentage (mean=77.1%) of targeted CpG sites and produced methylation level estimates that agreed with those generated from reduced representation bisulfite sequencing (R{superscript 2} = 0.98). Finally, we applied our protocol to profile age-associated DNA methylation variation in two subsistence-level populations--the Tsimane of lowland Bolivia and the Orang Asli of Peninsular Malaysia--and found age-methylation patterns that were strikingly similar to those reported in high income cohorts, despite known differences in age-health relationships between lifestyle contexts. Altogether, our optimized TMS protocol will enable cost-effective, population-scale studies of genome-wide DNA methylation levels across human and non-human primate species.

genomics↗

A novel behavioral apparatus for spontaneous exploration and operant conditioning of social information under spatial conditions in rats

BackgroundEvidence from the fields of evolutionary biology and neuroscience supports the theory that spatial cognition and social cognition share neural mechanisms. Rodent models are widely used to study either spatial or social cognition, but few studies have explored the interactions between the spatial and social cognitive domains due to the lack of appropriate paradigms. New methodOur study introduces the Vertical Maze (VM), a novel behavioral apparatus designed to measure multiple aspects of spatial and social cognition. The VM features a standard 3-chamber maze positioned above multilevel columns allowing for the presentation of conspecifics at varying spatial distances and familiarity levels. This arrangement enables conspecifics to serve as discriminative stimuli for both social and spatial spontaneous and goal-oriented assessments. The three-dimensional design of the VM allows rats to use multisensory cues to judge distance, direction, and social identity of conspecifics. ResultsIn the present study, we found that rats can 1) discriminate the spatial distance of conspecifics located below them in an operant conditioning task, and 2) discriminate social novelty when conspecifics are presented below at the near, middle, and far distances in a spontaneous exploration task. Critically, it was necessary for rats to explore all levels of the maze to perform these discriminations. Comparison with existing methodsThis new method advances the field by permitting the presentation of social information (conspecifics) at different spatial distances. The use of conspecifics to serve as stimuli for both social and spatial discriminations allows more direct comparison of behavioral measures across these information domains. Importantly, the presentation of conspecifics as stimuli below the 3-chamber level of the maze engages auditory, visual, and olfactory systems, encouraging a robust multisensory representation of conspecifics presented at a distance. ConclusionsOur results confirm that the VM is an effective tool for studying both spatial and social cognition, facilitating the development of novel automated tasks in these areas. This new method opens new avenues for investigating the neural and cognitive foundations of spatial and social behavior, as well as for exploring the possibility of shared mechanisms across these cognitive domains.

animal behavior and cognition↗

Trans-generational adaptation to maternal climate through hormone transport in plants

Whether organisms can inherit parental adaptations to the environment is a major question in evolutionary biology. Plant development is highly plastic and dependent on the seasonal cues which are used to control growth and reproduction. Seed dormancy and germination are key traits which respond strongly to temperature during seed development and here we show that progeny adaptation to seasonal climate is inherited from the mother plant. Loss of maternal LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) causes an inability of progeny seeds to sense temperature and this is linked mechanistically to reduced ABA levels in seeds and activation of the primary nitrate response. At the single cell level, small changes in temperature activate nitrate signalling specifically in the mother, and ABA biosensor imaging reveals temperature-dependent fluxes of ABA into seeds necessary for dormancy induction. Thus, we reveal that progeny seeds inherit the climate adaptation of mother plants via active hormone transport during seed set.

plant biology↗

Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana

Gamete killers are genetic loci that distort segregation in the progeny of hybrids because the killer allele promotes the elimination of the gametes that carry the sensitive allele. They are widely distributed in eukaryotes and are important for understanding genome evolution and speciation. We had previously identified a pollen killer in hybrids between two distant natural accessions of Arabidopsis thaliana. This pollen killer involves three genetically linked genes, and we previously reported the identification of the gene encoding the antidote that protects pollen grains from the killer activity. In this study, we identified the two other genes of the pollen killer by using CRISPR-Cas9 induced mutants. These two genes are necessary for the killer activity that we demonstrated to be specific to pollen. The cellular localization of the pollen killer encoded proteins indicates that the pollen killer activity involves the mitochondria. Sequence analyses reveal predicted domains from the same families in the killer proteins. In addition, the C-terminal half of one of the killer proteins is identical to the antidote, and one amino acid, crucial for the antidote activity, is also essential for the killer function. Investigating more than 700 worldwide accessions of A. thaliana, we confirmed that the locus is subject to important structural rearrangements and copy number variation. By exploiting available de novo genomic sequences, we propose a scenario for the emergence of this pollen killer in A. thaliana. Furthermore, we report the co-occurrence and behavior of killer and sensitive genotypes in several local populations, a prerequisite for studying gamete killer evolution in the wild. This highlights the potential of the Arabidopsis model not only for functional studies of gamete killers but also for investigating their evolutionary trajectories at complementary geographical scales. Author SummaryCertain genetic elements are qualified as selfish because they favor their transmission to the progeny during reproduction to the detriment of gametes that do not carry them. These elements are widespread in fungi as well as in plants or in animals, and they are made up of two or even three components, which are specific to each species. Therefore, they must be studied on a case-by-case basis. Moreover, understanding how they appear and propagate in local population remains a major issue in evolutionary biology. Here we have characterized, in the model plant Arabidopsis, the three genes involved in such an element, called a pollen killer. This pollen killer targets the mitochondria to cause the death of pollen grains that do not carry it. We investigated the three genes in several hundred genotypes collected worldwide, giving us a global view of their diversity at the species level. We also found that some French local populations contain both sensitive and killer plants, which constitutes an invaluable resource for studying the evolution of a pollen killer in the wild.

genetics↗

PAV-spotter: using signal cross-correlations to identify Presence/Absence Variation in target capture data

High throughput sequencing technologies have become essential in the fields of evolutionary biology and genomics. When dealing with non-model organisms or genomic gigantism, sequencing whole genomes is still relatively costly and therefore reduced-genome representations are frequently obtained, for instance by target capture approaches. While computational tools exist that can handle target capture data and identify small-scale variants such as single nucleotide polymorphisms and micro-indels, options to identify large scale structural variants are limited. To meet this need, we introduce PAV-spotter: a tool that can identify presence/absence variation (PAV) in target capture data. PAV-spotter conducts a signal cross-correlation calculation, in which the distribution of read counts per target between samples of different a priori defined classes - e.g. male versus female, or diseased versus healthy - are compared. We apply and test our methodology by studying Triturus newts: salamanders with gigantic genomes that currently lack an annotated reference genome. Triturus newts suffer from a hereditary disease that kills half their offspring during embryogenesis. We compare the target capture data of two different types of diseased embryos, characterized by unique deletions, with those of healthy embryos. Our findings show that PAV-spotter helps to expose such structural variants, even in the face of medium to low sequencing coverage levels, low sample sizes, and background noise due to mis-mapped reads. PAV-spotter can be used to study the structural variation underlying supergene systems in the absence of whole genome assemblies. The code, including further explanation, is available through the PAV-spotter GitHub repository: https://github.com/Wielstra-Lab/PAVspotter.

bioengineering↗

Resolving the "Ontogeny Problem" in Vertebrate Paleontology

Ontogenetic change is a major source of phenotypic variation among members of a species and is often of greater magnitude than the anatomical differences that distinguish closely related species. Ontogeny has therefore become a problematic confounding variable in vertebrate paleontology, especially in study systems distant from extant crown clades, rendering taxonomic hypothesis testing (a fundamental process in evolutionary biology) rife with difficulty. Paleontologists have adopted quantitative methods to compensate for the perception that juvenile specimens lack diagnostic apomorphies seen in their adult conspecifics. Here, I critically evaluate these methods and the assumptions that guide their interpretation using a {micro}CT dataset comprising growth series of American and Chinese alligator. I find that several widespread assumptions are scientifically unjustifiable, and that two popular methods - geometric morphometrics and cladistic analysis of ontogeny - have unacceptably high rates of type II error and present numerous procedural difficulties. However, I also identify a suite of ontogenetically invariant characters that differentiate the living species of Alligator throughout ontogeny. These characters overwhelmingly correspond to anatomical systems that develop prior to (and play a signaling role in) the development of the cranial skeleton itself, suggesting that their ontogenetic invariance is a consequence of the widely conserved vertebrate developmental program. These observations suggest that the architecture of the cranium is fixed early in embryonic development, and that ontogenetic remodeling does not alter the topological relationships of the cranial bones or the soft tissue structures they house. I propose a general model for future taxonomic hypothesis tests in the fossil record, in which the hypothesis that two specimens different ontogenetic stages of a single species can be falsified by the discovery of character differences that cannot be attributed plausibly to ontogenetic variation.

paleontology↗

Landmark-based estimates of genomic disparity

Chromosomal architecture has played a key role in the evolution of biodiversity. Detecting structural variants (SVs) on chromosomes has informed the study of speciation, sex determination, adaptation, and some of the earliest divergences in the tree of life. Here we present a computationally non-intensive approach, based on geometric morphometrics, that uses conserved DNA sequences as landmarks to quantify structural disparities of focal chromosomes across multiple species, individuals, or cell types. Based on two approaches, we show that this geno-metric method can be applied at micro- and macroevolutionary scales to discover and diagnose SVs. Using human X-linked genes and ultraconserved elements as landmarks, we provide empirical demonstrations with amniote sex chromosomes, the Drosophila virilis group, and placental mammal genomes. Landmark-based structural disparity analysis effectively identifies chromosomal rearrangements and has parallels with traditional morphometrics regarding chromosome size, landmark orientation and landmark availability. Using simulations, we show that structural disparity inferred from ultraconserved elements is correlated with overall levels of chromosome evolution; an attribute which is consistent with observed disparity between and within mammalian orders. We found that the disparity patterns of SVs have significant phylogenetic signal, giving them broad importance for studying evolutionary biology. Structural disparity analyses are a valuable addition to the comparative genomic toolkit in that they offer an intuitive, rapid mechanism for detecting SVs associated with single copy genetic landmarks and the potential to reveal broader patterns of chromosome evolution related to expansions, contractions, rearrangements and phylogeny.

genomics↗