ERC2.0 evolutionary rate covariation update improves inference of functional interactions across large phylogenies.

Evolutionary rate covariation (ERC) is an established comparative genomics method that identifies sets of genes sharing patterns of sequence evolution, which suggests shared function. Whereas many functional predictions of ERC have been empirically validated, its predictive power has hitherto been limited by its inability to tackle the large numbers of species in contemporary comparative genomics data sets. This study introduces ERC2.

Prediction of local convergent shifts in evolutionary rates with phyloConverge.

Motivation: Convergence analysis can characterize genetic elements underlying morphological adaptations. However, its performance on regulatory elements is limited due to their modular composition of transcription factor motifs, which have rapid turnover and experience different evolutionary pressures.

Results: We introduce phyloConverge, a phylogenetic method that performs scalable, fine-grained local convergence analysis of genomic elements at flexible length scales.

Convergent reduction of olfactory genes and olfactory bulb size in mammalian species at altitude.

The invasion of specialized ecological niches can cause drastic changes to selection regimes, resulting in genomic and phenotypic transformation. High-altitude habitats offer an excellent opportunity to investigate the genetic basis of local adaptation, as the repeated specialization of multiple lineages for high altitude has produced striking examples of convergent evolution, adaptation, and changes in their underlying genes. Although enlightening, this focus on adaptation has left aspects of evolution in high-altitude locations understudied-including the role of gene loss and pseudogenization, maladaptation and trait loss, and physiological aspects outside of respiration and gas exchange.

Integrating Intermediate Traits in Phylogenetic Genotype-to-Phenotype Studies.

A major goal of research in evolution and genetics is linking genotype to phenotype. This work could be direct, such as determining the genetic basis of a phenotype by leveraging genetic variation or divergence in a developmental, physiological, or behavioral trait. The work could also involve studying the evolutionary phenomena (e.

Congenital Aphakia Associated With a Pathogenic Variant: A Case Report.

Congenital aphakia is a rare eye condition in which the lens fails to form properly. It is typically caused by pathogenic variants within the or genes; however, it can also be associated with pathogenic variants. should be included in the genetic testing of patients with this condition.

Mammalian retinal specializations for high acuity vision evolve in response to both foraging strategies and morphological constraints.

Vision is a complex sensory system that requires coordination among cellular and morphological traits, and it remains unclear how functional relationships among traits interact with ecological selective pressures to shape the evolution of vision. Many species have specialized high visual acuity regions in the retina defined by patterns of ganglion cell density, which may evolve in response to ecological traits. For example, ganglion cell density can increase radially towards the center of the retina to form an area centralis, which is thought to improve acuity towards the center of the visual field in predators.

ERC 2.0 - evolutionary rate covariation update improves inference of functional interactions across large phylogenies.

Evolutionary Rate Covariation (ERC) is an established comparative genomics method that identifies sets of genes sharing patterns of sequence evolution, which suggests shared function. Whereas many functional predictions of ERC have been empirically validated, its predictive power has hitherto been limited by its inability to tackle the large numbers of species in contemporary comparative genomics datasets. This study introduces ERC2.

Impact of cytochrome P-450 3A4 enzyme/P-glycoprotein inducing antiseizure medications on direct oral anticoagulant therapy.

Objectives: Concomitant use of cytochrome P-450 and P-glycoprotein (CYP 3A4/P-gp) inducing antiseizure medications and direct oral anticoagulants (DOAC) may result in reduced DOAC effectiveness, but study results are inconsistent and of variable quality. The purpose of this study was to assess the safety of concomitant CYP 3A4/P-gp inducing antiseizure medications and DOAC use.

Methods: This was a retrospective cohort study of adult patients who were newly, concomitantly receiving a DOAC (apixaban, dabigatran, or rivaroxaban) and either a CYP 3A4/P-gp inducer (carbamazepine, phenytoin, phenobarbital, or primidone) or noninducer (gabapentin).

The Shu complex interacts with the replicative helicase to prevent mutations and aberrant recombination.

Homologous recombination (HR) is important for DNA damage tolerance during replication. The yeast Shu complex, a conserved homologous recombination factor, prevents replication-associated mutagenesis. Here we examine how yeast cells require the Shu complex for coping with MMS-induced lesions during DNA replication.

Phylogenetic Signal in Primate Tooth Enamel Proteins and its Relevance for Paleoproteomics.

Ancient tooth enamel, and to some extent dentin and bone, contain characteristic peptides that persist for long periods of time. In particular, peptides from the enamel proteome (enamelome) have been used to reconstruct the phylogenetic relationships of fossil taxa. However, the enamelome is based on only about 10 genes, whose protein products undergo fragmentation in vivo and post mortem.

Unearthing the secrets of Australia's most enigmatic and cryptic mammal, the marsupial mole.

The marsupial moles are arguably Australia's most enigmatic marsupials. Almost indistinguishable from placental (eutherian) moles, they provide a striking example of convergent evolution. Exploring the genome of the southern marsupial mole, we provide insights into its unusual biology.

Minus the Error: Testing for Positive 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.

Visualizing liquid-liquid phase transitions.

Liquid-liquid phase condensation governs a wide range of protein-protein and protein-RNA interactions in vivo and drives the formation of membrane-less compartments such as the nucleolus and stress granules. We have a broad overview of the importance of multivalency and protein disorder in driving liquid-liquid phase transitions. However, the large and complex nature of key proteins and RNA components involved in forming condensates such as stress granules has inhibited a detailed understanding of how condensates form and the structural interactions that take place within them.

RERconverge Expansion: Using Relative Evolutionary Rates to Study Complex Categorical Trait Evolution.

Comparative genomics approaches seek to associate molecular evolution with the evolution of phenotypes across a phylogeny. Many of these methods lack the ability to analyze non-ordinal categorical traits with more than two categories. To address this limitation, we introduce an expansion to RERconverge that associates shifts in evolutionary rates with the convergent evolution of categorical traits.

Evolutionary rate covariation is pervasive between glycosylation pathways and points to potential disease modifiers.

Mutations in glycosylation pathways, such as N-linked glycosylation, O-linked glycosylation, and GPI anchor synthesis, lead to Congenital Disorders of Glycosylation (CDG). CDG typically present with seizures, hypotonia, and developmental delay but display large clinical variability with symptoms affecting every system in the body. This variability suggests modifier genes might influence the phenotypes.

Protein G-quadruplex interactions and their effects on phase transitions and protein aggregation.

The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation.

Evolutionary rate covariation is a reliable predictor of co-functional interactions but not necessarily physical interactions.

Co-functional proteins tend to have rates of evolution that covary over time. This correlation between evolutionary rates can be measured over the branches of a phylogenetic tree through methods such as evolutionary rate covariation (ERC), and then used to construct gene networks by the identification of proteins with functional interactions. The cause of this correlation has been hypothesized to result from both compensatory coevolution at physical interfaces and nonphysical forces such as shared changes in selective pressure.

Exploring the impacts of social media and crowdsourcing on disaster resilience.

Social media and crowdsourcing (SMCS) are increasingly proving useful for addressing the effects of natural and human-made hazards. SMCS allow different stakeholders to share crucial information during disaster management processes and to strengthen community resilience through engagement and collaboration. To harvest these opportunities there is a need for better knowledge on SMCS for diverse disaster scenarios.

Use of Peripheral Intravenous Access in Patients Undergoing Chemotherapy for Testicular Cancer.

Purpose: Systemic chemotherapy, depending on the regimen, can be administered through peripheral intravenous (pIV) access or through central venous access devices (CVADs). There is no current best practice regarding optimal access for chemotherapy for patients with testicular cancer (TC). We retrospectively evaluated patients undergoing systemic chemotherapy for TC and compared baseline characteristics and complications of patients using pIV versus CVADs.

Sociodemographic and health-related differences in undiagnosed hypertension in the health survey for England 2015-2019: a cross-sectional cohort study.

Background: Hypertension is a leading cause of morbidity and mortality worldwide, yet a substantial proportion of cases are undiagnosed. Understanding the scale of undiagnosed hypertension and identifying groups most at risk is important to inform approaches to detection.

Methods: In this cross-sectional cohort study, we used data from the 2015 to 2019 Health Survey for England, an annual, cross-sectional, nationally representative survey.

RERconverge Expansion: Using Relative Evolutionary Rates to Study Complex Categorical Trait Evolution.

Comparative genomics approaches seek to associate evolutionary genetic changes with the evolution of phenotypes across a phylogeny. Many of these methods, including our evolutionary rates based method, RERconverge, lack the capability of analyzing non-ordinal, multicategorical traits. To address this limitation, we introduce an expansion to RERconverge that associates shifts in evolutionary rates with the convergent evolution of multi-categorical traits.

Protein G-quadruplex interactions and their effects on phase transitions and protein aggregation.

The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation.

Sperm competition intensity shapes divergence in both sperm morphology and reproductive genes across murine rodents.

It remains unclear how variation in the intensity of sperm competition shapes phenotypic and molecular evolution across clades. Mice and rats in the subfamily Murinae are a rapid radiation exhibiting incredible diversity in sperm morphology and production. We combined phenotypic and genomic data to perform phylogenetic comparisons of male reproductive traits and genes across 78 murine species.