Reply to: "Prior surveillance can bias cross-sectional validation of novel HCC biomarkers: Incumbent test bias".
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Assessment of Methodological Bias in Studies Reporting Racial Differences in Retinopathy of Prematurity in the United States.
PURPOSE: To assess methodological biases in studies reporting racial and ethnic differences in retinopathy of prematurity (ROP). METHODS: Systematic review of peer-reviewed studies published between 2014 and 2024 that reported on ROP outcome measures by race, ethnicity, or social determinants of health (SDOH). Three reviewers independently assessed each observation for selection and collider bias using definitions derived from perinatal epidemiology literature. Findings were also compared using a structured comparative synthesis between studies with and without identified methodological bias. RESULTS: A structured PubMed search identified 78 articles; 13 met inclusion criteria, with one study contributing two distinct analytical approaches, yielding 14 total observations. Survivorship bias was identified in 6 of 14 observations (42.9%), primarily due to the exclusion of infants who died prior to ROP screening. Potential collider bias was most common, found in 9 of 14 observations (64.3%), and was introduced through adjustment or stratification by gestational age and/or birthweight. Three studies did not exhibit either assessed biases. Among studies with identified bias, 8 of 10 observations reported lower ROP risk among Black versus White infants, whereas 3 of 4 observations without identified bias reported higher ROP risk or incidence among Black infants. CONCLUSION: Methodological biases in ROP studies investigating race or ethnicity are prevalent. Adjustment for gestational age or birthweight may introduce spurious race-ROP associations and contribute to paradoxical findings. Further exploration of the impact of SDOH on disease outcomes may reduce the misattribution of race as a biological risk factor and improve the interpretation of ROP disparities.
Collider bias↗
Premature closure underlies bias in medical diagnosis in students: A randomised controlled experiment.
OBJECTIVE: The purpose of the study reported in this article was to shed light on the cognitive mechanism mediating between biasing information and diagnostic error. The literature suggests at least two different hypotheses: premature closure leading biased participants to spend less time on diagnosis or increased competition between diagnostic hypotheses. The latter hypothesis predicts that biased participants would spend more time reaching a diagnosis. METHOD: Using the salient distracting findings (SDF) experimental paradigm, we biased 58 fourth-year medical students while diagnosing 12 clinical vignettes in a within-group incomplete block design under three conditions: cases presented without SDF, with SDF at the beginning and with SDF at the end. For each of these conditions, diagnostic accuracy, the number of SDF-related mistakes and time per word needed to process the case were recorded. The data were analysed using linear mixed modelling. Estimated marginal mean scores were reported. RESULTS: Participants confronted with salient distracting features (SDFs) at the beginning of a clinical case demonstrated significantly lower diagnostic accuracy (mean 0.11) compared with the No-SDF condition (0.27), representing a 61% reduction (F2,693 = 11.995, p < 0.001), and made more SDF-related mistakes (F2, 693 = 16.395, p < 0.001). When SDFs were presented at the end of the case, diagnostic accuracy was also reduced (mean 0.17; 36% reduction), but processing time did not differ from the No-SDF condition. Only early presentation of SDFs was associated with reduced processing time per word (F2,636 = 4.799, p < 0.01), consistent with premature closure. CONCLUSION: These findings demonstrate that biasing information increases diagnostic error in medical students and that only early bias is associated with reduced information processing. The data do not support the competition hypothesis for early bias, as processing time did not increase under biasing conditions. Premature closure can therefore be directly observed rather than inferred, inviting further research.
Humans↗
How, When, and for Whom Does Daily Weight Bias Internalization Undermine Body Image Satisfaction? A Daily Diary Study of Perceived Weight, Exercise Duration, and Gender Differences Among Adolescents.
Although body image satisfaction is increasingly recognized as a dynamic experience that fluctuates across daily contexts, little is known about how weight bias internalization shapes these fluctuations or the cognitive mechanisms and contextual factors involved. The present study examined whether perceived weight mediates the association between weight bias internalization and body image satisfaction, whether exercise duration moderates this association, and whether these effects differ by gender. Daily diary data were collected over 10 consecutive days from 305 Chinese adolescents (Mage = 12.59 years, SD = 0.63 years; 49.2% girls). Multilevel analyses revealed that, at both within- and between-person levels, higher weight bias internalization was associated with lower body image satisfaction. Perceived weight significantly mediated the association between weight bias internalization and body image satisfaction at both levels. Additionally, exploratory analyses using dynamic structural equation modeling further indicated that perceived weight mediated the relationship between weight bias internalization and body image satisfaction at the between-person level, but not at the within-person level. Furthermore, exercise duration moderated the association between perceived weight and body image satisfaction among female adolescents but not among male adolescents. Specifically, the negative association between perceived weight and body image satisfaction was stronger on days when girls engaged in more exercise than usual and among girls with higher average exercise duration. In addition, exercise duration moderated the indirect association between weight bias internalization and body image satisfaction through perceived weight at both within- and between-person levels among girls. These findings highlight the dynamic cognitive processes linking weight bias internalization to body image satisfaction, and the importance of considering gender and daily exercise context in understanding adolescents' body image experiences.
Humans↗
Codon bias variation in Staphylococcus aureus.
BACKGROUND: Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. METHODS: The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. RESULTS: CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). CONCLUSIONS: Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.
Staphylococcus aureus↗
GCfix: a fast and accurate fragment length-specific method for correcting GC bias in cell-free DNA.
MOTIVATION: Cell-free DNA (cfDNA) analysis has wide-ranging clinical applications due to its noninvasive nature. However, cfDNA fragmentomics and copy number analysis can be complicated by GC bias. There is a lack of GC correction software based on rigorous cfDNA GC bias analysis. Furthermore, there is no standardized metric for comparing GC bias correction methods across large sample sets, nor a rigorous experiment setup to demonstrate their effectiveness on cfDNA data at various coverage levels. RESULTS: We present GCfix, a method for robust GC bias correction in cfDNA data across diverse coverages. Developed following an in-depth analysis of cfDNA GC bias at the region and fragment length levels, GCfix is both fast and accurate. It works on all reference genomes and generates correction factors, tagged BAM files, and corrected coverage tracks. We also introduce two orthogonal performance metrics for (i) comparing the fragment count density distribution of GC content between expected and corrected samples, and (ii) evaluating coverage profile improvement post-correction. GCfix outperforms existing cfDNA GC bias correction methods on these metrics. AVAILABILITY AND IMPLEMENTATION: GCfix software and code for reproducing the figures are publicly accessible on GitHub: https://github.com/Rafeed-bot/GCfix_Software.
Software↗
PATTY corrects open chromatin bias for improved bulk and single-cell CUT&Tag profiling.
Precise profiling of epigenomes is essential for better understanding chromatin biology and gene regulation. Cleavage Under Targets & Tagmentation (CUT&Tag) is an efficient epigenomic profiling technique that can be performed on a low number of cells and at the single-cell level. With its growing adoption, CUT&Tag datasets spanning diverse biological systems are rapidly accumulating in the field. CUT&Tag assays use the hyperactive transposase Tn5 for DNA tagmentation. Tn5's preference toward accessible chromatin alters CUT&Tag sequence read distributions in the genome and introduces open chromatin bias that can confound downstream analysis, an issue more substantial in sparse single-cell data. We show that open chromatin bias extensively exists in published CUT&Tag datasets, including those generated with recently optimized high-salt protocols. To address this challenge, we present PATTY (Propensity Analyzer for Tn5 Transposase Yielded bias), a comprehensive computational method that corrects open chromatin bias in CUT&Tag data by leveraging accompanying ATAC-seq. By integrating transcriptomic and epigenomic data using machine learning and integrative modeling, we demonstrate that PATTY enables accurate and robust detection of occupancy sites for both active and repressive histone modifications, including H3K27ac, H3K27me3, and H3K9me3, with experimental validation. We further develop a single-cell CUT&Tag analysis framework built on PATTY and show improved cell clustering when using bias-corrected single-cell CUT&Tag data compared to using uncorrected data. Beyond CUT&Tag, PATTY sets a foundation for further development of bias correction methods for improving data analysis for all Tn5-based high-throughput assays.
Journal Article↗
PATTY corrects open-chromatin bias for improved bulk and single-cell CUT&Tag profiling.
Precise profiling of epigenomes is essential for better understanding chromatin biology and gene regulation. Cleavage Under Targets & Tagmentation (CUT&Tag) is an efficient epigenomic profiling technique that can be performed on a low number of cells and at the single-cell level. With its growing adoption, CUT&Tag datasets spanning diverse biological systems are rapidly accumulating in the field. CUT&Tag assays use the hyperactive transposase Tn5 for DNA tagmentation. Tn5's preference toward accessible chromatin alters CUT&Tag sequence read distributions in the genome and introduces open-chromatin bias that can confound downstream analysis, an issue more substantial in sparse single-cell data. We show that open-chromatin bias extensively exists in published CUT&Tag datasets, including those generated with recently optimized high-salt protocols. To address this challenge, we present PATTY (Propensity Analyzer for Tn5 Transposase Yielded bias), a comprehensive computational method that corrects open-chromatin bias in CUT&Tag data by leveraging accompanying ATAC-seq. By integrating transcriptomic and epigenomic data using machine learning and integrative modeling, we demonstrate that PATTY enables accurate and robust detection of occupancy sites for both active and repressive histone modifications, including H3K27ac, H3K27me3, and H3K9me3, with experimental validation. We further develop a single-cell CUT&Tag analysis framework built on PATTY and show improved cell clustering when using bias-corrected single-cell CUT&Tag data compared to using uncorrected data. Beyond CUT&Tag, PATTY sets a foundation for further development of bias correction methods for improving data analysis for all Tn5-based high-throughput assays.
Journal Article↗
Experiences of stigma, bias, and communication challenges among pregnant healthcare workers: A systematic review of qualitative evidence.
BACKGROUND: Healthcare work environments are fraught with occupational hazards that can impact pregnant healthcare workers' health as well as patient care. Despite the feminization of healthcare globally, systematic discrimination against pregnant workers persists across diverse healthcare settings and cultural contexts. The intersection of stigma, bias, and communication challenges creates substantial barriers to career advancement and wellbeing. However, no systematic review has synthesized qualitative evidence on how these three constructs interact across healthcare professions and cultural contexts using an integrated theoretical framework. OBJECTIVE: To systematically review and synthesize qualitative evidence on experiences of stigma, bias, and communication challenges among pregnant healthcare workers across different healthcare settings and cultural contexts using an integrated theoretical framework. DESIGN: Systematic review of qualitative studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with thematic synthesis. DATA SOURCES: Seven databases were searched from inception to January 2026. REVIEW METHODS: Included qualitative studies were appraised using the Critical Appraisal Skills Programme (CASP) checklist and synthesized through theory-guided thematic synthesis. Confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. RESULTS: Fourteen studies encompassing 1223 participants across 17 countries revealed four major themes: (1) professional identity stigma and workplace discrimination through systematic labeling and stereotyping; (2) gender-based institutional bias rooted in masculine organizational logic; (3) multilevel communication failures creating fear-based climates; and (4) individual and collective resistance strategies developed despite constraints. Occupational hazards specific to pregnancy included exposure to infectious diseases, imaging, physical tasks, cleaning products, patient violence, and medication administration. Support from coworkers and supervisors was identified as the most critical facilitator for avoiding hazards and making necessary modifications, while the desire to be 'supernurses' and fear of consequences emerged as significant barriers. These patterns were consistent across healthcare professions, settings, and cultural contexts, with specialty culture and healthcare system type moderating discrimination intensity. Confidence in core findings was rated high using GRADE-CERQual. CONCLUSIONS: Pregnant healthcare workers globally experience interconnected stigma, bias, and communication challenges that are systematically embedded within healthcare organizational structures. These challenges operate synergistically, requiring comprehensive multilevel interventions beyond policy compliance. Healthcare organizations must implement evidence-based strategies addressing stigma reduction, bias interruption, and communication transformation simultaneously to retain skilled workers and ensure quality patient care.
Female↗
β1- and β2-adrenergic Receptor Haplotypes Regulate Therapeutic Responses to Placebo and the Biased Ligand β-blocker Bucindolol.
BACKGROUND: ADRB1 and ADRB2, encoding cardiac myocyte β1- and β2-adrenergic receptors (ARs) that mediate pathologic myocardial remodeling in response to chronically increased signaling, contain N-terminus haplotype variants capable of influencing agonist- or biased ligand-induced receptor internalization that uncouples canonical signaling and initiates EGFR/ERK1/2 cardioprotection. METHODS: In two heart failure (HF) clinical trial genetic substudies we investigated effects of internalizing vs. internalization-resistant ADRB1/ADRB2 haplotypes on clinical or biomarker responses to the biased ligand β-blocker bucindolol vs. placebo or vs. the nonbiased β1-antagonist metoprolol, and in haplotyped isolated human heart preparations we measured ERK1/2 activation in response to these same interventions. RESULTS: In subjects with ≥3 internalizing ADRB1+ADRB2 haplotypes (6.7% subcohort) placebo treatment was associated with fewer clinical events compared to subjects with internalization-resistant haplotypes (Odds Ratio (OR) 0.28, 95% CI (0.10, 0.82)). In contrast, placebo treatment in subjects with ≥3 internalization-resistant haplotypes (70% subcohort) was associated with more clinical events in comparison to subjects with internalizing haplotype counterparts (OR 1.64 (1.46, 1.84)). Bucindolol treatment was equal to placebo in the ≥3 internalizing subcohort, but was superior to placebo in the internalization-resistant subcohort (bucindolol vs. placebo OR 0.49 (0.41, 0.58)). In subjects with all 4 haplotypes internalization-resistant (25% subcohort), bucindolol vs. placebo reduced time to first event rates by 62.3±17.5% (P <0.01, 1.68±0.34 fold > the all-haplotypes parent population and additive to 1.92±0.58 fold when the ADRB1 haplotype contained Arg389 rather than Gly389). The same bucindolol vs. placebo pattern was observed for NT-proBNP or norepinephrine reduction vs. metoprolol. In these comparisons ADRB2 and ADRB1 haplotypes behaved similarly, and although the haplotypes differed in frequency between Black and non-Black subjects, within haplotypes there were no by-race differences in therapeutic effects. Bucindolol but not metoprolol activated ERK1/2 signaling in isolated ventricular preparations with ≥3 internalization-resistant haplotypes. CONCLUSIONS: 1) Both β1- and β2-AR haplotypes regulate therapeutic responses in HF; internalizing species confer protection against clinical events in placebo-treated subjects, while in internalization-resistant haplotypes the biased ligand β-blocker bucindolol but not the non-biased ligand metoprolol is associated with favorable effects. 2) The biased ligand cardioprotective effect may be related to internalization-dependent or -independent ERK1/2 activation.
Beta Adrenergic Receptors↗
Uniparental inheritance of mitochondrial genes in yeast: dependence on input bias of mitochondrial DNA and preliminary investigations of the mechanism.
In Saccharomyces cerevisiae, previous studies on the inheritance of mitochondrial genes controlling antibiotic resistance have shown that some crosses produce a substantial number of uniparental zygotes, which transmit to their diploid progeny mitochondrial alleles from only one parent. In this paper, we show that uniparental zygotes are formed especially when one parent (majority parent) contributes substantially more mitochondrial DNA molecules to the zygote than does the other (minority) parent. Cellular contents of mitochondrial DNA (mtDNA) are increased in these experiments by treatment with cycloheximide, alpha-factor, or the uvsp5 nuclear mutation. In such a biased cross, some zygotes are uniparental for mitochondrial alleles from the majority parent, and the frequency of such zygotes increases with increasing bias. In two- and three-factor crosses the cap1, ery1, and oli1 loci behave coordinately, rather than independently; minority markers tend to be transmitted or lost as a unit, suggesting that the uniparental mechanism acts on entire mtDNA molecules rather than on individual loci. This rules out the possibility that uniparental inheritance can be explained by the conversion of minority markers to the majority alleles during recombination. Exceptions to the coordinate behavior of different loci can be explained by marker rescue via recombination. Uniparental inheritance is largely independent of the position of buds on the zygote. We conclude that it is due to the failure of minority markers to replicate in some zygotes, possibly involving the rapid enzymatic destruction of such markers. We have considered two general classes of mechanisms: (1) random selection of molecules for replication, as for example by competition for replicating sites on a membrane; and (2) differential marking of mtDNA molecules in the two parents, possibly by modification enzymes, followed by a mechanism that "counts" molecules and replicates only the majority type. These classes of models are distinguished genetically by the fact that the first predicts that the output frequency of a given allele among the progeny of a large number of zygotes will approximately equal the average input frequency of that allele, while the second class predicts that any input bias will be amplified in the output. The data suggest that bias amplification does occur. We hypothesize that maternal inheritance of mitochondrial or chloroplast genes in many organisms may depend upon a biased input of organelle DNA molecules, which usually favors the maternal parent, followed by failure of the minority (paternal) molecules to replicate in many or all zygotes.
Alleles↗
Parent-of-origin effects on allelic expression bias in interspecific poplar hybrids.
In hybrid plants, phenotypic outcomes are governed by interactions between the two parental genomes. However, the mechanisms underlying the interplay of divergent regulatory networks from these genomes remain poorly understood. In this study, we compared gene-level and allele-specific expression patterns, as well as differentially enriched pathways between F₁ and complex backcross (CBC) lines derived from a natural interspecific hybrid population of Populus fremontii (Pf) and P. angustifolia (Pa). Metabolic differences between Pf and Pa which exhibit low and high levels respectively of phenylpropanoid-derived condensed tannins were leveraged. Using individualized transcriptome references, differential expression and clustering analyses revealed CBC-biased and F₁-biased expression for genes involved in phenylpropanoid metabolism and photosynthesis, respectively. Biased expression of these genes at the allele level was also observed in F1. At the whole-transcriptome level, Pa-biased genes predominated in F₁ hybrids, and Pa alleles displayed more conserved expression patterns than Pf alleles across examined samples. Further analyses indicated that allelic expression bias was significantly associated with parental origin, which could be driven by sequence variations in cis-regulatory elements and differences in CpG island length. Our findings demonstrate strong parent-of-origin effects on divergent regulatory networks governing gene expression in poplar hybrids and provide clues for strategic parental selection tailored to specific metabolic pathways of interest.
cis-regulation↗
Structure-guided discovery of non-catechol dopamine D1 receptor ligands with biased agonism and antagonism.
The catechol L-DOPA, a cornerstone of Parkinson's disease (PD) treatment, has two major drawbacks: poor pharmacokinetics and, more significantly, debilitating dyskinesias from chronic dopamine D1 receptor (D1R) activation. Preclinical rodent studies suggest that D1R antagonism or β-arrestin-biased agonism can alleviate these motor complications, highlighting the need for next-generation non-catechol ligands. Through virtual screening, we identified eight novel chemotypes as D1R ligands, including two G protein-biased agonists, two β-arrestin-biased agonists and four antagonists. Structure-activity relationship (SAR) optimization led to the development of A82R, a non-catechol D1R antagonist (Ki 733 nM) with high D1 family over D2 family selectivity. Additionally, we present A69, a novel non-catechol β-arrestin-biased partial agonist for D1R (Ki 86.9 nM, stronger than representative D1R commercial drugs) with a sustained half-life of 1 h in the mouse brain. We show that the observed selectivity patterns are consistent with structural and information-theoretic limits on dopamine's ability to encode receptor subtype identity. Within these bounds, the non-catechol ligand chemotypes represent promising leads for developing therapies that modulate D1R signaling and reduce L-DOPA-induced dyskinesia in PD.
Receptors, Dopamine D1↗
Racial and sexual bias in psychiatric diagnosis: psychiatrists and other mental health professionals compared by race, sex, and discipline.
In a study designed to test for sex- and race-related bias in psychiatric diagnosis, the responses of 173 mental health professionals to four hypothetical patient profiles were analyzed. Minimal racial bias was observed. In some instances, therapists appeared more likely to make judgments biased against patients who were of the same race and sex as themselves. The results support the contention that hysterical and antisocial personality disorders are sex-biased diagnoses. The race of the therapist strongly influenced diagnosis. It is argued that this finding reflects resistance of nonwhite therapists to a majority-group-dominated diagnostic theory. Professional discipline rarely affected diagnosis with the exception that psychiatrists were more prone to diagnose psychosis.
Adult↗
Beauty bias in butterfly research and conservation.
Conservation biases have been documented since the first emergence of the concept of biodiversity in the 1980s,1,2,3 showing a systematic disproportion in the allocation of research and conservation efforts among taxa.4,5,6,7,8,9,10,11 One factor underlying this disproportion, gaining prominence in recent literature, is species' perceived beauty, shaped by human visual preferences.12,13,14,15,16,17 Here, we integrate a large-scale survey of the perceived beauty of European butterflies yielding >21,000 survey completions from >100 countries into a time-explicit network linking species' beauty, public attention, research and conservation efforts, and the EU regulatory framework. We found that species beauty is consistently associated with public attention, research, and conservation efforts in a temporally structured pattern compatible with a cumulative beauty bias. Research effort and public attention concentrate on widespread and visually attractive species, whereas species included in the legal conservation framework, particularly the Convention on the Conservation of European Wildlife and Natural Habitats (hereafter, Bern Convention, BC, 1979)18 and the EU Habitats Directive (hereafter, HD, 1992)19 are disproportionately represented by visually appealing and historically protected taxa. Because these frameworks guide funding and management actions, early associations between species beauty and BC/HD inclusion have contributed to long-lasting institutional patterns in butterfly research and conservation. By contrast, European IUCN Red Lists20,21 do not overrepresent beautiful species and identify more inconspicuous taxa as threatened. This mismatch reveals a tension between scientific assessments of extinction risk and historically embedded conservation priorities. Our findings suggest that recognizing beauty bias is vital for aligning conservation with actual ecological urgency. VIDEO ABSTRACT.
Animals↗
Nonhypermutator Cancers Access Driver Mutations Through Reversals in Germline Mutational Bias.
Cancer is an evolutionary disease driven by mutations in asexually reproducing somatic cells. In asexual microbes, bias reversals in the mutation spectrum can speed adaptation by increasing access to previously undersampled beneficial mutations. By analyzing tumors from 20 tissues, along with normal tissue and the germline, we demonstrate this effect in cancer. Nonhypermutated tumors reverse the germline mutation bias and have consistent spectra across tissues. These spectra changes carry the signature of hypoxia, and they facilitate positive selection in cancer genes. Hypermutated and nonhypermutated tumors thus acquire driver mutations differently: hypermutated tumors by higher mutation rates and nonhypermutated tumors by changing the mutation spectrum to reverse the germline mutation bias.
Neoplasms↗
Navigating Sampling Bias in Discrete Phylogeographic Analysis: Assessing the Performance of an Adjusted Bayes Factor.
Bayesian phylogeographic inference is widely used in molecular epidemiological studies to reconstruct the dispersal history of pathogens. Discrete phylogeographic analysis treats geographic locations as discrete traits and infers lineage transition events among them, and is typically followed by a Bayes factor (BF) test to assess the statistical support. In the standard BF (BFstd) test, the relative abundance of the involved trait states is not considered, which can be problematic in the case of unbalanced sampling. Existing methods to correct sampling bias in discrete phylogeographic analyses using continuous-time Markov chain (CTMC) model, often require additional epidemiological information to balance the sampling effort among locations. As such data is not necessarily available, alternative approaches that rely solely on available genomic data are needed. In this perspective, we assess the performance of a modification of the BFstd, the adjusted Bayes factor (BFadj), which incorporates information on the relative abundance of samples by location when inferring support for transition events and root location inference without requiring additional data. Using a simulation framework, we assess the statistical performance of BFstd and BFadj under varying levels of sampling bias, estimating their type I and type II error rates. Our results show that BFadj complements the BFstd by reducing type I errors at the cost increasing type II errors for inferred transition events, while improving type I and type II errors in root location inference. Our findings provide guidelines for implementing the complementary BFadj to detect and mitigate sampling bias in discrete phylogeographic inference using CTMC modeling.
Bayes Theorem↗
Positive selection and relaxed purifying selection contribute to rapid evolution of sex-biased genes in green seaweed Ulva.
BACKGROUND: The evolution of differences in gamete size and number between sexes is a cornerstone of sexual selection theories. The green macroalga Ulva, with incipient anisogamy and parthenogenetic gametes, provides a unique system to investigate theoretical predictions regarding the evolutionary pressures that drive the transition from isogamy to anisogamy, particularly in relation to gamete size differentiation and sexual selection. Its minimal gamete dimorphism and facultative parthenogenesis enable a rare window into early evolutionary steps toward anisogamy. RESULTS: By analyzing the expression profiles of sex-biased genes (SBGs) during gametogenesis, we found that SBGs evolve faster than unbiased genes, driven by higher rates of non-synonymous substitution (dN), indicating that SBGs are under stronger selective pressures. Mating type minus-biased genes (mt-BGs) exhibit higher dN/dS values than mating type plus-biased genes (mt+BGs), suggesting stronger selective pressures on mt-BGs, although this difference was not statistically significant (P = 0.08). Using branch-site and RELAX models, we found positive selection and relaxed purifying selection acting on a significant proportion of SBGs, particularly those associated with flagella function. CONCLUSIONS: This study highlights the selective pressures shaping anisogamy and provides insights into the molecular mechanisms underlying its evolution. The faster evolution of SBGs, particularly mt-BGs, and the positive selection on genes associated with motility, such as those related to flagella function, suggest the importance of enhanced gamete motility in the transition to anisogamy. These findings contribute to our understanding of sexual selection and the evolutionary forces that drive the differentiation of gamete size and number between sexes.
Selection, Genetic↗