Biology subjects

Yu, F.

Publications and source records attributed to Yu, F..

At least 109 records · Page 6Linked to original sources

bioRxiv2023

TTG2 defines trichome cell shape by modulating microtubules and actin cytoskeleton in Arabidopsis

The Arabidopsis TRANSPARENT TESTA GLABRA2 (TTG2) gene encodes a WRKY transcription factor that regulates a range of development events like trichome, seed coat, and atrichoblasts formation. Loss-of-function of TTG2 was previously shown to reduce or eliminate trichome branching. Here, we report the identification of a new allele of TTG2, ttg2-6. In contrast to the ttg2 mutants described before, ttg2-6 displays unique trichome phenotypes. Some ttg2-6 mutant trichomes are hyperbranched, whereas others are hypobranched, distorted, or clustered. Further, we found that in addition to specifically activating R3 MYB transcription factor TRIPTYCHON (TRY) to promote trichome branching, TTG2 also integrates cytoskeletal signaling to regulate trichome morphogenesis. The ttg2-6 trichomes display aberrant cortical microtubules (cMTs) and cortical actin filaments (F-actin) configurations. Moreover, genetic and biochemical analysis showed that TTG2 could directly bind and regulate the expression of BRICK1 (BRK1), a subunit of the actin nucleation promoting complex SCAR/WAVE. Collectively, taking advantage of ttg2-6, we uncovered new functions for TTG2 in facilitating cMT and F-actin cytoskeleton-dependent trichome development. Our evidence for a direct relationship between TTG2 and cytoskeletal regulators establishes an unprecedented understanding of cellular signaling events downstream of the core transcriptional regulation during trichome development in Arabidopsis.

developmental biology↗

bioRxiv2023

The soil emergence-related transcription factor PIF3 regulates root penetration by interacting with the receptor kinase FER

The cotyledons of etiolated seedlings from terrestrial flowering plants must emerge from the soil surface, while roots must penetrate the soil to ensure plant survival. We show here that the soil emergence-related transcription factor PHYTOCHROME-INTERACTING FACTOR 3 (PIF3) regulates root penetration via transducing external signals perceived by the receptor kinase FERONIA (FER) in Arabidopsis thaliana. The loss of FER function in the fer-4 mutant resulted in a severe defect in root penetration into hard soil or medium. Single-cell RNA-seq profiling of roots revealed a distinct cell clustering pattern, especially for root cap cells, and revealed PIF3 as one of FER-regulated transcription factor. Biochemical, imaging, and genetic experiments confirmed that PIF3 is required for root penetration into soil. Moreover, FER interacted with and stabilized PIF3, which then modulated the expression of mechanosensitive ion channel and the sloughing of outer cells in the root cap. Based on these findings, we propose a novel mechanism of soil penetration by plant roots.

plant biology↗

bioRxiv2023

Structural preferences shape the entropic force of disordered protein ensembles

Intrinsically disordered protein regions (IDRs) make up over 30% of the human proteome and instead of a native, well-folded structure exist in a dynamic conformational ensemble. Tethering IDRs to a surface (for example, the surface of a well-folded region of the same protein) can reduce the number of accessible conformations in IDR ensembles. This reduces the ensembles conformational entropy, generating an effective entropic force that pulls away from the point of tethering. Recent experimental work has shown that this entropic force causes measurable, physiologically relevant changes to protein function, but how the magnitude of this force depends on the IDR sequence remains unexplored. Here we use all-atom simulations to analyze how structural preferences encoded in dozens of IDR ensembles contribute to the entropic force they exert upon tethering. We show that sequence-encoded structural preferences play an important role in determining the magnitude of this force and that compact, spherical ensembles generate an entropic force that can be several times higher than more extended ensembles. We further show that changes in the surrounding solutions chemistry can modulate IDR entropic force strength. We propose that the entropic force is a sequence-dependent, environmentally tunable property of terminal IDR sequences.

biophysics↗

bioRxiv2022

Androgen-mediated TGFβ expression suppresses anti-tumor neutrophil response in bone metastatic prostate cancer

Prostate Cancer (PCa) bone metastases are associated with spinal cord compression, fracture, bone pain and death. Despite advances in the medical therapy for localized disease, metastatic disease is incurable and osseous progression is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that tumor bone neutrophils are tumoricidal to PCa but lose their cytotoxic potential as the tumor progresses. However, there have been no studies to date to clinically define and characterize neutrophils throughout the prostate cancer disease spectrum to determine their biomarker potential. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identify that PCa progression dictates PMN properties, including viability, cell surface markers and gene expression. However, the majority of PMNs elicited an anti-tumor response ex vivo demonstrating that PMN cytotoxicity is cell autonomous and independent of PCa disease stage. In fact, we identify a novel role for androgen regulation, i.e., androgen deprivation therapy (ADT), in suppressing PMN cytotoxicity via altered transforming growth factor beta receptor I (T{beta}RI). Using preclinical models, we found that high dose testosterone/bipolar androgen therapy (BAT) and genetic or pharmacologic T{beta}RI inhibition combined with standard ADT rescued the androgen-associated suppression and restored PMN anti-tumor immune response. This combination provided a therapeutic strategy more impactful than ADT alone, in bone metastatic prostate cancer (BM-PCa). These studies: 1) highlight a necessity for both molecular and functional characterization of PMNs per cancer type and 2) reveals the ability to program PMN immune response for successful targeting of BM-PCa.

cancer biology↗

bioRxiv2022

Large-scale analysis of the N-terminal regulatory elements of the kinase domain in plant receptor-like kinase family

The N-terminal regulatory element of the kinase domain (NRE), which includes juxtamembrane segment (JM) of Receptor-like kinases (RLKs) and the N-terminal extension segment of the kinase domain in RLCKs, is the key component that regulates the activities of RLKs and RLCKs. However, their feature and functions remain largely unexplored. Herein, we perform a systematic analysis of 510,233 NRE sequences in RLKs and RLCKs from 528 plants by integrating information theory and genome-wide analysis to unravel their common characteristics and diversity. Recombinant RLKs are used to explore the structural-functional relationship of the newly-discovered motifs in vitro. Most NRE segments are around 40-80 amino acids, featuring a serine-rich region and a 14-amino-acid motif FSYEELEKATBNFS which harbors a characteristic -helix connecting to the core kinase domain. This -helix suppresses FERONIAs kinase activity. Motif discovery algorithm has identified 29 motifs with known phosphorylation sites highly conserved in RLK and RLCK classes, especially the motif VGPWKpTGLpSGQLQKAFVTGVP in LRR-VI-2 class. The NRE phosphorylation of an LRR-VI-2 member MDIS1 modulates the auto-phosphorylation of its co-receptor MIK1, indicating NREs potential role as a "kinase switch" in RLK activation. Consequently, the characterization of phosphorylatable NRE motifs improves the accuracy in predicting phosphorylatable serines. Altogether, our study provides an enriched and comprehensive dataset to investigate NRE segments from individual RLKs and helps understand the underlying mechanism of action of the RLK signal transduction and kinase activation processes in plant adaptation.

plant biology↗

bioRxiv2022

HLA-Glyco: A large-scale interrogation of the glycosylated immunopeptidome

MHC-associated peptides (MAPs) bearing post-translational modifications (PTMs) have raised intriguing questions regarding their attractiveness for targeted therapies. Here, we developed a novel computational glyco-immunopeptidomics workflow that integrates the ultrafast glycopeptide search of MSFragger with a glycopeptide-focused false discovery rate (FDR) control. We performed a harmonized analysis of 8 large-scale publicly available studies and found that glycosylated MAPs are predominantly presented by the MHC class II. We created HLA-Glyco, a resource containing over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. Our comprehensive resource reveals high levels of truncated glycans, conserved HLA-binding cores, and differences in glycosylation positional specificity between classical HLA class II allele groups. To support the nascent field of glyco-immunopeptidomics, we include the optimized workflow in the FragPipe suite and provide HLA-Glyco as a free web resource.

immunology↗

bioRxiv2022

cpSRP54 and FtsH cooperate thylakoid membrane associated proteostasis during de-etiolation in Arabidopsis thaliana

The thylakoid membrane protein quality control, which requires the coordination of membrane protein translocation and degradation of unassembled proteins, determines the chloroplast development during de-etiolation. Despite numerous efforts, the regulation of this progress in land plants is largely unknown. Here, we reported the isolation and characterization of pga4 mutants with defects in chloroplast development during de-etiolation. Map-based cloning and complementation assay confirmed that PGA4 encodes the chloroplast signal recognition particle 54 kDa protein (cpSRP54). A heterogeneous LhcB2-GFP was generated as an indicative substrate for cpSRP54-mediated thylakoid translocation. LhcB2-GFP were not assembled into functional complexes, and degraded to a short form dLhcB2-GFP during de-etiolation, through an N-terminal degradation initiated on thylakoid membranes. Further biochemical and genetic evidences demonstrated that the degradation of LhcB2-GFP to dLhcB2-GFP was disrupted in pga4, and var2 mutants caused by mutations in the VAR2/AtFtsH2 subunit of thylakoid FtsH. The yeast two-hybrid assay showed that the N-terminus of LhcB2-GFP which was degraded consequently, interacts with the protease domain of VAR2/AtFtsH2 in yeasts. Moreover, the over-accumulated LhcB2-GFP in pga4 and var2, formed protein aggregates, which were insoluble in mild nonionic detergents. Genetically, cpSRP54 is a new suppressor locus for the leaf variegation phenotype of var2. Those together demonstrated the coordination of cpSRP54 and thylakoid FtsH in maintenance of thylakoid membrane protein quality control during the assembly of photosynthetic complexes, and provided a trackable substrate and product for monitoring the cpSRP54-dependent protein translocation and the FtsH-dependent protein degradation. One Sentence SummaryWe revealed the coordination of cpSRP54 and FtsH in thylakoid membrane protein quality control, and provided a trackable marker for monitoring the activity of cpSRP54 and thylakoid FtsH protease.

plant biology↗

bioRxiv2022

One-stop analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform

Liquid chromatography (LC) coupled with data-independent acquisition (DIA) mass spectrometry (MS) has been increasingly used in quantitative proteomics studies. Here, we present a fast and sensitive approach for direct peptide identification from DIA data, MSFragger-DIA, which leverages the unmatched speed of the fragment ion indexing-based search engine MSFragger. MSFragger-DIA conducts a database search of the DIA tandem mass (MS/MS) spectra prior to spectral feature detection and peak tracing across the LC dimension. We have integrated MSFragger-DIA into the FragPipe computational platform for seamless support of peptide identification and spectral library building from DIA, data dependent acquisition (DDA), or both data types combined. We compared MSFragger-DIA with other DIA tools, such as DIA-Umpire based workflow in FragPipe, Spectronaut, and in silico library-based DIA-NN and MaxDIA. We demonstrated the fast and sensitive performance of MSFragger-DIA across a variety of sample types and data acquisition schemes, including single-cell proteomics, phosphoproteomics, and large-scale tumor proteome profiling studies.

bioinformatics↗

bioRxiv2022

Fear of missing out (FOMO) associates with reduced cortical thickness in core regions of the posterior default mode network and higher levels of problematic smartphone and social media use

Fear of missing out (FOMO) promotes the desire or urge to stay continuously connected with a social reference group and updated on their activities, which may result in escalating and potentially addictive smartphone and social media use. The present study aimed to determine whether the neurobiological basis of FOMO encompasses core regions of the reward or social brain, and the associations with the level of problematic smartphone or social media use. We capitalized on a dimensional neuroimaging approach to examine cortical thickness and subcortical volume associations in a comparably large sample of healthy young individuals (n = 167). Meta-analytic network and behavioral decoding were employed to further characterize the identified regions. Higher levels of FOMO associated with lower cortical thickness in the precuneus. In contrast, no associations between FOMO and variations in striatal morphology were observed. Meta-analysis decoding revealed that the identified precuneus region exhibited a strong functional interaction with the default mode network (DMN) engaged in social cognitive and self-referential domains. Together the present findings suggest that individual variations in FOMO are associated with the brain structural architecture of the right precuneus, a core hub within a large-scale functional network resembling the DMN involved in social and self-referential processes. FOMO may promote escalating social media and smartphone use via social and self-referential processes rather than reward-related processes per se.

neuroscience↗

bioRxiv2022

STIM1 signals through NFAT independently of Orai1 and SOCE to regulate breast cancer cell migration

Store-operated calcium entry (SOCE) contributes to several physiological and pathological conditions including transcription, secretion, immunodeficiencies, and cancer. SOCE has been shown to be important for breast cancer cell migration where knockdown of SOCE components (STIM1 or Orai1) decreases cancer metastasis. Here we show unexpectedly that STIM1 knockout (KO) metastatic MDA-MB-231 breast cancer cells migrate faster and have enhance invasion capacity compared to parental cells. In contrast, Orai1-KO cells, which have similar levels of SOCE inhibition as STIM1-KO, migrate slower than the parental cell line. This shows that the enhanced migration phenotype of STIM1-KO cells is not due to the loss of a Ca2+ entry through SOCE, rather it involves transcriptional remodeling. Interestingly, NFATC2 is significantly downregulated in STIM1-KO cells and overexpression of NFATC2 reversed the enhanced migration of STIM1-KO cells. This demonstrates that STIM1 modulates NFATC2 expression independently of its role in SOCE. SUMMARY STATEMENTBreast cancer cells migrate faster when the ER Ca2+ sensor STIM1 in knocked out due to downregulation of NFAT1 expression independent of Ca2+ influx.

cell biology↗

bioRxiv2022

MSBooster: Improving Peptide Identification Rates using Deep Learning-Based Features

Peptide identification in liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments relies on computational algorithms for matching acquired MS/MS spectra against sequences of candidate peptides using database search tools, such as MSFragger. Here, we present a new tool, MSBooster, for rescoring peptide-to-spectrum matches using additional features incorporating deep learning-based predictions of peptide properties, such as LC retention time, ion mobility, and MS/MS spectra. We demonstrate the utility of MSBooster, in tandem with MSFragger and Percolator, in several different workflows, including nonspecific searches (immunopeptidomics), direct identification of peptides from data independent acquisition data, single-cell proteomics, and data generated on an ion mobility separation-enabled timsTOF MS platform. MSBooster is fast, robust, and fully integrated into the widely used FragPipe computational platform.

bioinformatics↗

bioRxiv2022

MSFragger-Labile: A Flexible Method to Improve Labile PTM Analysis in Proteomics

Post-translational modifications of proteins play essential roles in defining and regulating the functions of the proteins they decorate, making identification of these modifications critical to understanding biology and disease. Methods for enriching and analyzing a wide variety of biological and chemical modifications of proteins have been developed using mass spectrometry (MS)-based proteomics, largely relying on traditional database search methods to annotate resulting mass spectra of modified peptides. These database search methods treat modifications as static attachments of a mass to particular position in the peptide sequence, but many modifications undergo fragmentation in tandem MS experiments alongside, or instead of, the peptide backbone. While this fragmentation can confound traditional search methods, it also offers unique opportunities for improved searches that incorporate modification-specific fragment ions. Here, we present a new Labile Mode in the MSFragger search engine that can tailor modification-centric searches to the fragmentation observed. We show that labile mode can dramatically improve spectrum annotation rates of phosphopeptides, RNA-crosslinked peptides, and ADP-ribosylated peptides. Each of these modifications presents distinct fragmentation characteristics, showcasing the flexibility of MSFragger labile mode to improve search for a wide variety of biological and chemical modifications.

bioinformatics↗

bioRxiv2022

Expression of Microcystis biosynthetic gene clusters in natural populations suggests temporally dynamic synthesis of novel and known secondary metabolites in western Lake Erie

SummaryMicrocystis spp. produces diverse secondary metabolites within freshwater cyanoHABs around the world. In addition to the biosynthetic gene clusters (BGCs) encoding known compounds, Microcystis genomes harbor numerous BGCs of unknown function, indicating its poorly understood chemical repertoire. While recent studies show that Microcystis produces several metabolites in the lab and field, little work has focused on analyzing the abundance and expression of its broader suite of BGCs during cyanoHAB events. Here, we use metagenomic and metatranscriptomic approaches to track the relative abundance of Microcystis BGCs and their transcripts throughout the 2014 western Lake Erie cyanoHAB. Results indicate the presence of several transcriptionally active BGCs that are predicted to synthesize both known and novel secondary metabolites. The abundance and expression of these BGCs shifted throughout the bloom, with transcript abundance levels correlating with temperature, nitrate and phosphorus concentrations, and the abundance of co-occurring predatory and competitive eukaryotic microorganisms, suggesting the importance of both abiotic and biotic controls in regulating expression. This work highlights the need for understanding the chemical ecology and potential risks to human and environmental health posed by secondary metabolites that are produced but unmonitored, as well as the potential discovery of pharmaceutical compounds from cyanoHAB-derived BGCs. Originality-Statement of SignificanceMicrocystis spp. dominate cyanobacterial harmful algal blooms (cyanoHABs) worldwide and pose significant threats to water quality through the production of numerous secondary metabolites, many of which are toxic. While the toxicity and biochemistry of microcystins and several other compounds have been well studied, the broader suite of secondary metabolites produced by Microcystis remains poorly understood, leaving gaps in our understanding of their impacts on ecology, human and ecosystem health, or potential pharmaceutical application. In this study, we use metagenomic and transcriptomic datasets to examine the diversity of genes encoding synthesis of secondary metabolites in natural Microcystis populations and assess their patterns of transcription in the context of biotic and abiotic conditions in western Lake Erie cyanoHABs. Our results reveal the presence of a large diversity of both known gene clusters that encode toxic secondary metabolites as well as novel ones that encode cryptic compounds. This research highlights the need for targeted studies of the secondary metabolite diversity in western Lake Erie, a vital freshwater source to the United States and Canada.

microbiology↗

bioRxiv2022

Mining for ions: diagnostic feature detection in MS/MS spectra of post-translationally modified peptides

Post-translational modifications (PTMs) are an area of great interest in proteomics, with a surge in methods to detect them in recent years. However, PTMs can introduce complexity into proteomics searches by fragmenting in unexpected ways. Detecting post-translational modifications in mass spectrometry-based proteomics traditionally relies on identifying ions shifted by the masses of the modifications. This presents challenges for many PTMs. Labile PTMs lose part of their modification mass during fragmentation, rendering shifted fragment ions unidentifiable, and isobaric PTMs are indistinguishable by mass, requiring other diagnostic ions for disambiguation. Furthermore, even modifications that have undergone extensive characterization often produce different fragmentation patterns across instruments and conditions. To address these deficiencies and facilitate the next generation of PTM identification, we have developed a method to automatically find diagnostic spectral features for any PTM, allowing subsequent searches to take advantage of additional metrics and increase PTM identification and localization rates. The method has been incorporated into the open-search annotation tool PTM-Shepherd and the FragPipe computational platform.

bioinformatics↗

bioRxiv2022

Wounding promotes root regeneration through a cell wall integrity sensor, the receptor kinase FERONIA

Wounding caused by various stresses is the initial event of plant regeneration. However, the mechanisms underlying the early wounding responses to promote plant regeneration remain largely unknown. Here, we report that the receptor kinase FERONIA (FER) interacts with Topless/Topless-related proteins (TPL/TPRs) to regulate the expression of regeneration-related genes to modulate root tip regeneration. One ligand of FER, rapid alkalinization factor 33 (RALF33), is stimulated by wounding and functions together with FER to promote regeneration. Single-cell sequencing data showed that the low-differentiation cell types in the stele may account for the enhanced regeneration ability in the fer mutant, especially in the columella and quiescent center (QC). Further interaction assays and analysis of the gene expression patterns in low-differentiation cell types confirmed that FER interacts with TPL/TPRs to regulate the expression of downstream regeneration-related genes. One of their downstream targets, an essential transcription factor (TF) in root regeneration, ERF115, acts downstream of FER-TPL/TPRs to control regeneration. Our results suggested a signaling pathway between the early wounding response and regeneration processes in roots. One-sentence summaryRALF33-FER serves as an early signaling module between wounding and regeneration by functioning with TPL/TPRs in roots.

cell biology↗

bioRxiv2022

Capturing the Hierarchically Assorted Modules of Protein Interaction in the Organized Nucleome

Nuclear proteins are major constituents and key regulators of the topological organization of nucleome. To elucidate the global connectivity of nucleomic proteins and to decipher the hierarchically organized modules of protein interaction that are involved in nucleomic organization and nuclear events, both formaldehyde and CBDPS crosslinkers were applied sequentially on the in vivo prefixed nuclei to perform a double chemical crosslinking with mass spectrometry (XL-MS) analysis. The integration of dimethyl-labelling with XL-MS generated a quantitative XL-MS workflow (qXL-MS) that consequently identified 5,340 cross-linked peptides (crosslinks) from nucleome. These crosslinks were construed into 1,297 nuclear protein-protein interactions (PPIs), from which discovered were 250 and 26 novel interactors of histones and nucleolar box C/D snoRNP complex, respectively. MONET-based modulomic analysis of their Arabidopsis orthoglous PPIs constructed 27 and 24 master nuclear protein interaction modules (NPIMs) that contain the condensate-forming protein(s) and the intrinsically disordered region (IDR)-containing proteins, respectively. These NPIMs successfully captured the previously reported nuclear protein complexes and nuclear bodies in nucleome. Surprisingly, modulomic analysis showed that these NPIMs were hierarchically assorted into four communities of NPIMs in nucleome including Genome Community and Nucleolus Community. The qXL-MS-based quantitative interactomics finally revealed 17 Hormone-specific module variants participating in a broad range of nuclear events. Thus, this integrated pipeline of qXL-MS and MONET modulomics, named as CHAMPION, is capable of capturing both nuclear protein complexes and nuclear bodies, constructing the topological architecture of protein interaction modules and module variants in nucleome and probably of mapping the protein compositions of condensates. HighlightsO_LIThe formaldehyde and CBDPS crosslinkers coupled qXL-MS discovered 5,340 crosslinked peptides. These crosslinks were construed into 1,297 nuclear protein-protein interactions (PPIs), protein components of which contained 250 and 26 novel interactors of histone octamer and nucleolar box C/D snoRNP complex, respectively, in the intricately organized nucleome. C_LIO_LIThe MONET-based modulomic analysis of these crosslinks captured 95 nuclear protein interaction modules (NPIMs), a portion of which contain both the condensate-forming and the intrinsically disordered region (IDR)-containing proteins. Especially, some NPIMs captured 6 previously reported nuclear protein complexes. C_LIO_LIA number of Hormone-specific module variants were identified by modulomics upon hormone treatment using the hormone significantly up-regulated crosslinks from qXL-MS. Several PPIs and NPIMs have been substantiated with alternative biological experiments. C_LIO_LIThis CHAMPION pipeline has partitioned these NPIMs into four hierarchically and topologically organized communities in nucleome. The molecular functions of those proteins partitioned into C1 and C2 community are specialized in genome organization and nucleolar functions, respectively. C_LI

bioinformatics↗

bioRxiv2022

Persistent Hypersomnia Following Repetitive Mild Experimental Traumatic Brain Injury: Roles of Chronic Stress and Sex Differences

Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience a spectrum of exposures over a prolonged period under stressful conditions. Understanding the effects of complex exposures can support proper evaluation and care for patients experiencing persistent symptoms. We designed a longitudinal series of non-invasive procedures in adult mice to evaluate the effects of prolonged mild exposures. We assessed anxiety, depression, and sleep-wake dysfunction as symptoms that can impact long term outcomes after mild TBI. Unpredictable chronic mild stress (UCMS) was generated from a variable sequence of environmental stressors distributed within each of 21 days. Subsequently, mice received a mild blast combined with closed-head mild TBI on five days at 24-hour intervals. TBI components were either five linear force impacts, or a novel alternating repetitive mild TBI (Ar-mTBI) model of linear and rotational (CHIMERA) impacts over five days to produce diffuse pathology. In males and females, UCMS induced anxiety without depressive behavior. Persistent hypersomnia, specifically increased sleep during the active dark period, was found through 6-12 month time points in male mice receiving UCMS with repetitive blast plus TBI events, or surprisingly after UCMS alone. Sleep-wake dysfunction was not found with TBI events alone and was not found in females under any conditions. These results identify prolonged stress and sex differences as important considerations for sleep-wake dysfunction. Furthermore, this reproducible hypersomnia is similar to excessive daytime sleepiness reported in patients, which may inform treatments.

neuroscience↗

bioRxiv2022

Estimating temporally variable selection intensity from ancient DNA data with the flexibility of modelling linkage and epistasis

Innovations in ancient DNA (aDNA) preparation and sequencing technologies have exponentially increased the quality and quantity of aDNA data extracted from ancient biological materials. The additional temporal component from the incoming aDNA data can provide improved power to address fundamental evolutionary questions like characterising selection processes that shape the phenotypes and genotypes of contemporary populations or species. However, utilising aDNA to study past selection processes still involves considerable hurdles like how to eliminate the confounding factor of genetic interactions in the inference of selection. To address this issue, we extend the approach of He et al. (2022) to infer temporally variable selection from the aDNA data in the form of genotype likelihoods with the flexibility of modelling linkage and epistasis in this work. Our posterior computation is carried out by a robust adaptive version of the particle marginal Metropolis-Hastings algorithm with a coerced acceptance rate. Our extension inherits the desirable features of He et al. (2022) such as modelling sample uncertainty resulting from the damage and fragmentation of aDNA molecules and reconstructing underlying gamete frequency trajectories of the population. We evaluate its performance through extensive simulations and show its utility with an application to the aDNA data from pigmentation loci in horses.

genetics↗