Biology subjects

Zhang, L.

Publications and source records attributed to Zhang, L..

At least 361 records · Page 20Linked to original sources

bioRxiv2025

A Cattle BodyMap of Transcriptome across 52 Tissues and 3 Developmental Stages Reveals New Genetic Insights into Beef Production Traits

Cattle are important livestock that provide essential meat and milk resources. However, a comprehensive analysis of gene expression, alternative splicing (AS), and RNA editing across various organs and developmental stages in cattle has not been reported. This study aims to create a comprehensive transcriptomic BodyMap across various tissues and developmental stages, integrating this information into genomic predictions of beef production traits. We created a comprehensive transcriptomic BodyMap using 400 samples collected from 52 organs of newborn, young, and adult cattle, and estimated their contributions to genetic variance and genomic predictions for 23 beef production traits in 1476 beef cattle. We cataloged the expression of 25,530 annotated genes, 28,533 novel long non-coding RNAs (lncRNAs), 215,754 AS events, and 3,093,058 A-to-I RNA-editing sites. Integrating transcriptome BodyMap with 23 beef production traits, we found lncRNAs influenced traits like rib-eye area and carcass length, while RNA editing associated with chunk roll weight and daily gain. We observed trait-relevant tissues between different stages, including the differential expressed genes of cerebellum, longissimus muscle, and testis between newborn and adult stages are more relevant to beef production traits. The tissue-specific genes and development-associated genes in several tissues could improve the reliability of genomic prediction in beef production traits. We developed Cattle BodyMap Transcriptome Database (https://cattlegenomics.online/cattle_bodymap) to retrieve, analyze, and visualize gene expression, lncRNA, splicing and RNA editing data. Our results demonstrated the potential of using transcriptome data as a valuable resource for genomic selection and breeding programs in beef cattle. Additionally, our transcriptome BodyMap serves as a valuable resource for biological interpretation, functional validation, and genomic improvement in livestock.

genomics↗

bioRxiv2025

The Calcium Pump ATP2B1/PMCA1 Regulates CNS Vascular Development by Facilitating Norrin- and WNT7A/B-induced Frizzled4 signaling

Frizzled4 (FZD4) is a receptor for Norrin and WNT7A/B ligands, is expressed in endothelial cells (ECs), is required for endothelial blood-central nervous system (CNS) barrier function as well as CNS angiogenesis, and transduces {beta}-catenin-dependent signaling. Despite its fundamental importance in neurovascular biology, including as a drug target, the molecular mechanisms governing FZD4 regulation remain poorly understood. Here, we employed proximity biotinylation to identify proteins that regulate FZD4. We identified ATPase Plasma Membrane Ca{superscript 2} Transporting 1 (ATP2B1, also known as PMCA1) as a FZD4 proximity interactor. Functional analyses revealed that ATP2B1 depletion increased EC Ca2+, activated NFAT, and significantly attenuated Norrin/Frizzled4 signaling. Endothelial-specific Atp2b1 deletion caused CNS vascular phenotypes consistent with compromised Norrin/Frizzled4 signaling. This study identifies ATP2B1 as a novel regulator of Norrin- and WNT7A/B-induced FZD4 signaling and suggests that in pathological contexts with elevated EC Ca2+-levels, EC function may be modulated by suppression of {beta}-catenin-dependent signaling.

developmental biology↗

bioRxiv2025

Two Spag6 genes control sperm formation and male fertility in mice

Sperm-associated antigen 6 (SPAG6) is the mammalian orthologue of Chlamydomonas PF16, a central axonemal protein essential for flagellar motility. In mice, two homologous genes have been identified: the ancestral Spag6 on chromosome 2 and the evolutionary derived Spag6l on chromosome 16. Although Spag6 knockout mice (Spag6-/-) are phenotypically normal, the surviving Spag6l-/- males are infertile. To further investigate the roles of SPAG6 and SPAG6L, we generated compound mutants by crossing the two knockout lines. Compound heterozygous Spag6+/-; Spag6l+/- mice are fertile, while all Spag6-/-; Spag6l+/- males are infertile despite grossly normal appearance. Histological and ultrastructural analyses revealed defective spermiogenesis, including abnormal chromatin condensation, malformed acrosome and manchette, and disorganized mitochondrial and fibrous sheath. Both SPAG6 and SPAG6L bind to SPINK2, a key regulator of acrosome function, but SPAG6 has an approximately 10-fold higher binding affinity than SPAG6L. Moreover, SPAG6 modulates testicular AKAP4 and SPAG16L levels, which are critical components of the fibrous sheath and central apparatus respectively. Notably, SPAG6 suppresses tubulin acetylation, whereas SPAG6L enhances this post-translational modification, suggesting antagonistic roles in microtubule assembly. Overall, our findings demonstrate that SPAG6 and SPAG6L coordinately regulate sperm formation and male fertility during evolution.

developmental biology↗

bioRxiv2025

Structural insights into Measles virus RNA synthesis: C protein-mediated regulation of replication-transcription switch and allosteric inhibition by ERDRP-0519

Nonsegmented negative-sense RNA viruses (nsNSVs) rely on a multifunctional RNA-dependent RNA polymerase (RdRP) complex for transcription and replication. In measles virus (MeV), the nonstructural protein C has long been implicated in regulating RNA synthesis, yet its precise role remains unclear. Here, we show that the MeV C protein directly associates with the RdRP complex. Using cryo-electron microscopy, we determined atomic-resolution structures of the MeV polymerase with and without C, revealing that C binding stabilizes the accessory domains of L and locks the complex into a replication-competent elongation state. Biochemical data further show that C promotes N protein recruitment, enhancing polymerase processivity through facilitating encapsidation during replication. Additionally, we also resolved high-resolution structures of MeV and Nipah virus (NiV) polymerases bound to ERDRP-0519, an orally available morbillivirus inhibitor. Unexpectedly, the compound occupies a previously unrecognized allosteric pocket within the RdRp domain, rather than the predicted PRNTase domain, overlapping conserved resistance sites. This binding induces conformational changes in palm subdomain, blocking RNA template and nucleotide engagement, thereby halting RNA synthesis. These findings uncover distinct regulatory and inhibitory mechanisms in paramyxovirus polymerases and provide a structural framework for the rational design of broad-spectrum antivirals targeting MeV, NiV, and potentially other clinically relevant nsNSVs.

microbiology↗

bioRxiv2025

Cross-disease comparison of dermatomyositis and lupus skin identifies inflammatory monocytes and JAK-1 signaling as drivers of vasculopathy in dermatomyositis

Dermatomyositis (DM) is a rare yet devastating autoimmune disease characterized by inflammatory and vasculopathic changes in skin and muscle. DM and systemic lupus erythematosus (lupus) skin lesions have overlapping clinical and histopathological features, yet disparate responses to available therapeutics. DM skin disease is often relapsing and recalcitrant. To investigate DM immunopathogenesis, non-lesional skin, lesional skin, and circulating immune cells from DM patients were analyzed using single-cell RNA-sequencing. Samples were analyzed in parallel with lesional and non-lesional lupus skin, healthy control skin, and peripheral blood. We demonstrate a pervasive type I interferon (IFN) signature in DM stroma that persists in culture and is distinguished from lupus by upregulation of VEGF and IL-18 signaling in DM keratinocytes. Furthermore, endothelial cells (ECs) in lesional DM exhibit decreased proliferation that was not observed in lupus. Using cell communication networks, we identified a population of DM-specific monocytes interacting with non-proliferating DM ECs. Co-culture of monocytes from DM patients with ECs resulted in increased EC apoptosis inhibited by JAK1 blockade. JAK1 inhibition also resulted in reversal of DM-stromal and inflammatory signatures. Together, our data provide a comprehensive cross-disease characterization of lesional and non-lesional skin of DM compared to lupus and implicate monocyte-mediated EC dysfunction in DM vasculopathy and support JAK inhibition for refractory skin disease.

immunology↗

bioRxiv2025

The role of Platelet-derived growth factor (PDGF) in uremic vascular calcification.

Vascular calcification is common in chronic kidney disease (CKD), contributing to increased cardiovascular morbidity and mortality. One of the proposed mechanisms of driving vascular calcification is a phenotypic switch of vascular smooth muscle cells (VSMCs). The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs), particularly PDGFR-{beta}, were shown to modulate the VSMC phenotype. However, their role in uremic vascular calcification remained unclear. We adapted an ex vivo calcification model using murine aortas to simulate uremic conditions. Compared to control conditions, incubation with hemodialysate from CKD patients or using aortas from CKD animals both resulted in significantly increased PDGFR-{beta} phosphorylation and vascular calcification. Inhibition of PDGF signaling using soluble PDGFR-{beta} or the small molecule tyrosine kinase inhibitor imatinib significantly reduced uremic calcification and enhanced vascular elasticity. Next, we generated transgenic mice with a VSMC-specific, inducible expression of constitutively active PDGFR-{beta}. The aortas of these mice exhibited significantly increased vascular calcification ex vivo, which was further aggravated by uremic conditions. We established an in vivo model of accelerated vascular calcification and CKD in the transgenic mice, showing significantly aggravated vascular calcification and phenotypic switching of VSMCs compared to non-transgenic littermates. Finally, increased expression of phosphorylated PDGFR-{beta} and a VSMC phenotypic switching were detected in human arteries from patients with CKD compared to those without CKD. In conclusion, PDGFR-{beta} contributes to CKD-associated vascular calcification, representing a potential novel therapeutic target.

systems biology↗

bioRxiv2025

Inferring Progressive Disconnection in Alzheimer's Disease with Probabilistic Boolean Networks

The modern understanding of Alzheimers disease as a disconnection syndrome presents the challenge of quantifying the directed influence between brain regions. To address this, we apply probabilistic Boolean networks to model effective brain connectivity for the first time, introducing a novel framework for analyzing functional magnetic resonance imaging data from a cohort comprising normal controls, individuals with mild cognitive impairment (MCI), and Alzheimers patients. Our robust statistical analysis identified five significant connections, each exhibiting a linear decline in influence throughout the disease spectrum. We observed a progressive disruption of pathways from the Default Mode Network to the Medial Temporal Lobe, capturing a key psychophysiological mechanism underlying Alzheimers disease. These findings demonstrate the potential of our framework as a powerful tool for modeling network-level dynamics in neurodegeneration.

bioinformatics↗

bioRxiv2025

Pluripotent stem cell-derived siTNK cells attack tumors via a synthetic CD8-CD28 TCR complex

Tumor-associated antigen-specific T cell receptor (TCR)-engineered T cells offer a promising strategy for cancer therapy. Natural killer (NK) cells exhibit broad anti-tumor activity with low side effects but lack the capacity to recognize intracellular antigens. Here, we found that the human pluripotent stem cell (hPSC)-derived iNK cells, unlike tissue-isolated NK cells, expressed all four CD3 subunits at the transcriptome level. We introduced a synthetic gene-expressing complex (SCOTR), encoding a tumor antigen- specific TCR, CD8 coreceptor, and CD28 costimulatory molecule, into hPSCs to generate SCOTR-hPSCs. The SCOTR-hPSCs gave rise to abundant synthetic TCR complex-expressing iNK (siTNK) cells via an organoid induction method. These siTNK cells showed HLA-dependent, antigen-specific cytotoxicity against tumor cells and significantly suppressed tumor growth in tumor xenograft animal models, while also preserving universal non-specific tumor-killing activity. Collectively, siTNK cells, as hPSC-derived hybrid cells with dual features of adaptive T and inherent NK cells, offer an artificial cell source for human immunotherapies.

immunology↗

bioRxiv2025

f-BGM enables fungi-specific genome mining in high accuracy and interpretability

Emerging artificial intelligence (AI)-based genome mining methods have revolutionized the paradigm of bacterial secondary metabolite (SM) discovery. Fortunately, recent data accumulation of fungal biosynthetic gene clusters (BGC) fairly offers opportunities for systematic development and evaluation of fungi-specific pipelines. In this work, we proposed a deep learning framework termed as f-BGM specifically for fungal genome mining. By designing a novel self-attention-based architecture to augment inter-domain associations in local genomic contexts, f-BGM exhibits superior performance over existing AI-based methods in both in-distribution and out-of-distribution benchmark tests for BGC detection. Further analyses demonstrate that f-BGM is of decent interpretability on deciphering single-domain and -protein importance, as well as inter-domain partnership. By establishing additional binary classification models, f-BGM also achieves high-quality identification of core enzymes within given BGCs. Finally, case studies of f-BGM-driven genome mining in marine fungi uncovers biosynthetic potential underestimated by the rule-based method antiSMASH, as supported by experimental and computational validation.

bioinformatics↗

bioRxiv2025

Methyl gallate Attenuates Post-Stroke Emotional and Cognitive Symptoms by Promoting Hippocampal Neurogenesis via PI3K/GSK3 and AMPK Signaling

Restoring hippocampal neurogenesis is an effective strategy for post-stroke recovery. Methyl gallate (MET) exhibits neuroprotective properties. However, the effect of MET in improving brain functional recovery in the post-stroke depression (PSD) model and its underlying mechanism remains unknown. Single-cell data analysis showed that the cell types and molecular characteristics of PSD are similar to those of primary depression but exhibit weaker synaptic plasticity and stronger inflammatory signals. In addition, molecular docking studies revealed that MET exhibits a significant binding capacity with AMPK/GSK3, suggesting that MET mediates the neuroprotective effects of both. In this study, we created a post-stroke depression (PSD) model by performing physical restraint after ischemia and tested the treatment effects of MET. We observed that MET significantly attenuated PSD-induced depressive-/anxiety-behaviors associated with a reduction of stress hormone corticosterone and ACTH levels. Morris water maze and recognition task results indicate that MET can also alleviate cognitive impairments in the PSD model. In the hippocampus of the PSD model, MET improved the proliferation and differentiation of neural stem/progenitor cells (NSPCs). MET treatment significantly enhanced the activity of AMPK and decreased the activity of GSK3{beta}. Furthermore, in primary neural progenitors under hypoxia, both the PI3K inhibitor LY294002 and the AMPK inhibitor compound C blocked the effects of MET to promote neural development. Animal experiments also confirmed that LY294002/compound C treatment could reduce the effects of MET in antidepressant behaviours. Taken together, our results indicate that PI3K, as well as AMPK-mediated adult neurogenesis, is restored by MET to improve brain functions in the PSD model.

neuroscience↗

bioRxiv2025

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

In the HIV antibody mediated prevention (AMP) trials, the broadly neutralizing antibody VRC01 demonstrated protective efficacy against new diagnoses with susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, we performed deep sequencing on 172 participants in the placebo and treatment arms, generating 63,444 gag-{Delta}pol (2.5 kb) and 53,088 rev-env-{Delta}nef (3 kb) sequences. Sequences were classified into transmitted founder lineages (TFLs), and infections with multiple distinct lineages were determined. Multilineage infections were detected in [~]38% of participants in both the African (HVTN 703/HPTN 081) and Americas/Europe (HVTN 704/HPTN 085) cohorts, regardless of placebo or treatment group, or cohort. The high levels of multilineage infections could be attributed to minor lineages (<5% abundance) identified in 20% of participants. Infection with VRC01 discordant viruses (IC80s >3-fold different) was observed in 40% of multilineage infections, with a trend toward greater intra-host neutralization differences with increasing VRC01 dose (Jonckheere-Terpstra test, p=0.072). In six VRC01 treated participants who acquired both sensitive (IC80<1{micro}g/ml) and resistant viruses (IC80>3{micro}g/ml), the sensitive lineages declined over time. Recombination was pervasive, observed in 63% of multilineage infections at the time of HIV diagnosis. In one treated participant infected with VRC01 discordant lineages, recombinant viruses preferentially inherited the resistance mutation (binomial p=0.004). In conclusion, our in-depth analysis of breakthrough viruses in the AMP trials revealed a high frequency of multilineage infections, including infections with viruses with different VRC01 sensitivities. This analysis also highlights the role of recombination in shaping intra-host viral evolution and facilitating escape from VRC01. SignificanceThis work advances our understanding of the diversity of initial viral infection and evolution and in vivo activity of broadly neutralizing antibodies (bNAbs). Deep sequencing revealed [~]38% of HIV acquisitions with multiple transmitted founder lineages, higher than previous studies. These occurrences were similar in the placebo and VRC01 groups. Viral recombination among post-acquisition variants was common under antibody selection and appeared to favor resistant sequences in the treatment group. These data suggest as with single antiviral therapy, passive and active immunization of bNAbs should be directed at multiple antigen targets of HIV-1.

molecular biology↗

bioRxiv2025

Simple k-RF Metrics for Comparison of Labeled DAGs

Causal relationships between different entities are often modeled as labeled acyclic digraphs (DAGs) in biology and healthcare, in particular for depicting the progression of malignant tumor cells. Comparison of labeled DAGs is essential for developing methods for inference and evaluation of DAG models. Therefore, a robust dissimilarity metric is critical for such comparison tasks. We introduce new dissimilarity measures for labeled DAGs by refining the k-Robinson-Foulds distance, originally defined to compare labeled trees. The new measures are defined based on the comparison of local node-induced multisets of labels. They can be used to compare DAGs with different label sets, without the need to introduce auxiliary nodes or remove existing ones.

evolutionary biology↗

bioRxiv2025

β-sheet stabilization of the island domain underlies ligand-induced LRR-RP activation of plant immune signaling

Leucine-rich repeat (LRR) receptor kinases (RKs) and receptor proteins (RPs) are important classes of plant pattern recognition receptors (PRRs) activating pattern-triggered immunity. While both classical and AI-based structural approaches have recently provided crucial insights into ligand-LRR-RK binding mechanisms, our understanding of ligand perception by LRR-RPs remains limited. In contrast to LRR-RKs, many LRR-RPs typically embed one or more loopout regions in their extracellular domains that are crucial for functionality. Here, we employed an AI-based approach to reveal a novel ligand-binding mechanism shared by the Arabidopsis LRR-RPs RLP23 and RLP42 - the PRRs for the short peptide ligands nlp20 and pg13, derived from NECROSIS- AND ETHYLENE-INDUCING PEPTIDE 1-like proteins (NLPs) and fungal endopolygalacturonases (PGs), respectively. This mechanism relies on a {beta}-strand interaction with the N-terminal part of the island domain (ID) loopout, which adopts an antiparallel {beta}-sheet conformation. Additionally, we investigated the larger and more complex binding interface of RLP32 - the PRR for proteobacterial TRANSLATION INITIATION FACTOR 1 (IF1), a folded protein ligand that requires its tertiary structure for recognition. Finally, we describe a mechanistic role of the ID for co-receptor recruitment conserved across LRR-RPs. Together, our results shed light on the ligand-binding mechanisms and receptor complex formation of this important class of PRRs. This opens avenues for a molecular understanding of the plant-pathogen co-evolution, as well as the engineering of plant immune receptors for crop disease resistance.

plant biology↗

bioRxiv2025

Morphological plasticity of endophytic Chitinophaga pinensis

Environmental changes, whether due to climate change or human influences, compromise the resilience of plants to biotic and abiotic stresses, such as pathogens, drought and heat. Plant microbiota are known to promote plant resilience. To be able to harness the power of the plant microbiome we need to identify microbiota with health-promoting properties. Recent studies have demonstrated that the bacterium Chitinophaga pinensis enhances plant health and increases resistance to fungal infections. Here, we show that C. pinensis exhibits an unusually high morphological plasticity, switching between a filamentous and a spherical cell state, each of which is characterized by a distinct transcriptional profile. Despite these transcriptional differences, spherical cells remained metabolically active and replicating, while lacking structural characteristics typically associated with dormant states. Furthermore, the spherical cell morphology of C. pinensis facilitates hitchhiking behaviour and motility via surfactin cheating, potentially influencing its dispersal and interactions within the plant microbiome. To investigate the structural dynamics and transcriptional adaptation of this plant endophyte, we applied a combination of microscopy and culture-based techniques. Taken together, our study provides new insights into the morphological flexibility and transcriptional regulation of the plant-beneficial C. pinensis.

microbiology↗

bioRxiv2025

De novo biosynthesis of alpinetin enhanced by directed evolution of 5-O-methyltransferase

Alpinetin ((2S)-7-Hydroxy-5-methoxyflavan-4-one) is a natural flavonoid found in various medicinal herbs and is frequently used in Chinese patent medicines. It exhibits a wide range of bioactivities, including anti-inflammatory, cardiovascular protective, lung protective, antiviral, hepatoprotective, and antitumor effects. Alpinetin features a 5-methyl group on the A ring, a rare characteristic among methylated flavonoids. The limited abundance of Alpinetin in plant biomass, its laborious extraction and purification from this biomass, and the toxicity and lack of regio- and chemoselectivity in organic synthesis render its biosynthesis in engineered microbes an attractive alternative. In this study, we aimed to achieve the de novo biosynthesis of alpinetin in Escherichia coli. In a series of optimization steps, we varied the selection of pathway enzymes, plasmid configurations, medium composition, and fermentation strategies. Lastly, we applied a directed evolution campaign to the 5-O-methyltransferase to successfully enable the de novo biosynthesis of alpinetin in E. coli for the first time. Moreover, we demonstrated the ability of O-methyltransferase to methylate a broad range of flavonoid substrates, leading to the production of valuable O-methylated flavonoids. Our study represents the first example of alpinetin biosynthesis in a heterologous host and paves the way to produce other valuable O-methylated flavonoids enzymatically.

biochemistry↗

bioRxiv2025

Intra-Tumoral Treg Ablation Unleashes NK Cell-Mediated Control of CD8 T Cell-Resistant Tumors

Cancer cells frequently lose MHC I to evade CD8+ T cell recognition. While Natural Killer (NK) cells are poised to target MHC I-deficient cancer cells, MHC I loss alone is often insufficient to unleash fully effective NK cell responses. Here we show that selective intra-tumoral (IT) ablation of regulatory T (Treg) cells elicited potent antitumor NK cell responses that controlled MHC I-deficient and even MHC I+ cancers. Tregs controlled the activation, maturation, and anti-tumor cytotoxic activity of NK cells within the tumor microenvironment. Mechanistically, IT Tregs prevented the cDC2-dependent induction of IL-2 production by CD4+ Tconv cells that was necessary for NK cell activation. Systemically administered antibodies that selectively depleted IT Tregs similarly empowered NK- dependent tumor control. These findings expand the breadth of Treg-mediated cancer immunosuppression to encompass antitumor NK cells and suggest that targeting Tregs in tumors can control CD8+ T cell-resistant cancers. One Sentence SummaryIT Treg ablation drives NK cell tumor control via CD4+ Tconv-derived IL-2, eliminating MHC I+/MHC I- cancers without systemic toxicity.

immunology↗

bioRxiv2025

Cross-talk between RNA secondary and three-dimensional structure prediction: a comprehensive study

In recent years, various computational methods have been developed to predict the three-dimensional (3D) structures of RNAs. Due to its hierarchical folding property, RNA secondary (2D) structure is usually used as input for 3D structure prediction to improve accuracy and efficiency. However, the extent to which the accuracy of input 2D structure affects the performance of 3D structure prediction remains to be further investigated. Additionally, whether and how the input base-pairing interactions are modified during the 3D structure modeling process is another question worth exploring. To address these issues, here we comprehensively benchmark five representative 3D structure prediction models on extensive datasets, using 2D structures of varied accuracies as input. Our results indicate that there is a pervasive cross-talk between RNA 2D and 3D structure predictions, where the performance dependence of 3D structure prediction on the accuracy of input 2D structure is closely associated with the 3D models ability to modify the input base-pairing interactions during structure modeling. Furthermore, we also observed that RNA 3D structure prediction performance is more sensitive to the occurrence of false positive base pairs in the input 2D structure than to true positive base pairs, suggesting a worthy direction to further improve the model performance. Author summaryThree-dimensional (3D) structural modeling of RNAs with large sizes and complex topologies remains challenging despite the availability of (predicted) 2D structures as constraints. Exploring the potential cross-talk between 2D and 3D structure predictions is a worthy direction to improve the performance of RNA structure modeling. In this study, we found that all tested popular RNA 3D structure prediction models were able to modify the original base pairing interactions contained in the input 2D structure during the 3D modeling process. Especially, all of these models presented increased F1-score for the optimal combination of RNA 2D and 3D structure prediction models. The results suggest that a worthwhile direction to further improve the performance of RNA 3D structure prediction is to minimize the incidence of incorrectly predicted base pairing interactions during modeling process without compromising or even improving the presence of correct interactions in the input 2D structure.

biophysics↗

bioRxiv2025

Genomic Evidence for Males of Exceptional Reproductive Output (ERO) in Apes and Humans

It is widely suspected that a small percentage of males have exceptional reproductive output (ERO) but progeny numbers of males are rarely measurable, even in humans. If we define the variance ratio of reproductive-output in males and females as = VM/VF, the ERO hypothesis would predict >>1. Since autosomal, X, and Y chromosomes are found in males 1/2, 1/3, and 100% of the time, their DNA diversities can inform about . For example, autosomal and Y-linked diversities are governed, respectively, by (VM+VF)/2 and VM. When comparing the chromosomal diversities, appears to be near 20 for chimpanzees and orangutans, and 1-10 for gorillas. The exception is bonobos with < 1. In humans, the extensive genomic data are coupled to a theory, developed herein, that can filter out selection influences on Y-linked diversities. Hence, the estimation of is rigorous, yielding values near or above 20, depending on the population. When >10, the presence of ERO males is very likely. These analyses can be applied more generally to species with XY sex determination.

evolutionary biology↗