No Time To Read

No Time To Read podcast S3E1 Plant carbonic anhydrase-like enzymes in neuroactive alkaloid biosynthesis Guest: Ryan Nett, Assistant Professor, Department of Molecular and cellular Biology, Harvard University Twitter/X: @rnett42 Host: Arif Ashraf, Assistant Professor, Department of Biology, Howard University Twitter/X: @aribidopsis --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Season 3 of the No Time To Read podcast is starting soon. Thanks for your support as an audience. --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: DNA methylation signatures of duplicate gene evolution in angiosperms Journal: Plant Physiology Year: 2023 Guest: Sunil Kenchanmane Raju Host: Arif Ashraf Abstract Gene duplication is a source of evolutionary novelty. DNA methylation may play a role in the evolution of duplicate genes (paralogs) through its association with gene expression. While this relationship has been examined to varying extents in a few individual species, the generalizability of these results at either a broad phylogenetic scale with species of differing duplication histories or across a population remains unknown. We applied a comparative epigenomic approach to 43 angiosperm species across the phylogeny and a population of 928 Arabidopsis (Arabidopsis thaliana) accessions, examining the association of DNA methylation with paralog evolution. Genic DNA methylation was differentially associated with duplication type, the age of duplication, sequence evolution, and gene expression. Whole-genome duplicates were typically enriched for CG-only gene body methylated or unmethylated genes, while single-gene duplications were typically enriched for non-CG methylated or unmethylated genes. Non-CG methylation, in particular, was a characteristic of more recent single-gene duplicates. Core angiosperm gene families were differentiated into those which preferentially retain paralogs and “duplication-resistant” families, which convergently reverted to singletons following duplication. Duplication-resistant families that still have paralogous copies were, uncharacteristically for core angiosperm genes, enriched for non-CG methylation. Non-CG methylated paralogs had higher rates of sequence evolution, higher frequency of presence–absence variation, and more limited expression. This suggests that silencing by non-CG methylation may be important to maintaining dosage following duplication and be a precursor to fractionation. Our results indicate that genic methylation marks differing evolutionary trajectories and fates between paralogous genes and have a role in maintaining dosage following duplication. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Extensive embryonic patterning without cellular differentiation primes the plant epidermis for efficient post-embryonic stomatal activities Journal: Developmental Cell Year: 2023 Guest: Margot Smit Host: Arif Ashraf Abstract Plant leaves feature epidermal stomata that are organized in stereotyped patterns. How does the pattern originate? We provide transcriptomic, imaging, and genetic evidence that Arabidopsis embryos engage known stomatal fate and patterning factors to create regularly spaced stomatal precursor cells. Analysis of embryos from 36 plant species indicates that this trait is widespread among angiosperms. Embryonic stomatal patterning in Arabidopsis is established in three stages: first, broad SPEECHLESS (SPCH) expression; second, coalescence of SPCH and its targets into discrete domains; and third, one round of asymmetric division to create stomatal precursors. Lineage progression is then halted until after germination. We show that the embryonic stomatal pattern enables fast stomatal differentiation and photosynthetic activity upon germination, but it also guides the formation of additional stomata as the leaf expands. In addition, key stomatal regulators are prevented from driving the fate transitions they can induce after germination, identifying stage-specific layers of regulation that control lineage progression during embryogenesis. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: A dolabralexin-deficient mutant provides insight into specialized diterpenoid metabolism in maize Journal: Plant Physiology Year: 2023 Guest: Katie Murphy Host: Arif Ashraf Abstract Two major groups of specialized metabolites in maize (Zea mays), termed kauralexins and dolabralexins, serve as known or predicted diterpenoid defenses against pathogens, herbivores, and other environmental stressors. To consider the physiological roles of the recently discovered dolabralexin pathway, we examined dolabralexin structural diversity, tissue-specificity, and stress-elicited production in a defined biosynthetic pathway mutant. Metabolomics analyses support a larger number of dolabralexin pathway products than previously known. We identified dolabradienol as a previously undetected pathway metabolite and characterized its enzymatic production. Transcript and metabolite profiling showed that dolabralexin biosynthesis and accumulation predominantly occur in primary roots and show quantitative variation across genetically diverse inbred lines. Generation and analysis of CRISPR-Cas9-derived loss-of-function Kaurene Synthase-Like 4 (Zmksl4) mutants demonstrated dolabralexin production deficiency, thus supporting ZmKSL4 as the diterpene synthase responsible for the conversion of geranylgeranyl pyrophosphate precursors into dolabradiene and downstream pathway products. Zmksl4 mutants further display altered root-to-shoot ratios and root architecture in response to water deficit. Collectively, these results demonstrate dolabralexin biosynthesis via ZmKSL4 as a committed pathway node biochemically separating kauralexin and dolabralexin metabolism, and suggest an interactive role of maize dolabralexins in plant vigor during abiotic stress. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Transcriptional responses to gibberellin in the maize tassel and control by DELLA domain proteins Journal: The Plant Journal Year: 2022 Guest: Norman Best Host: Arif Ashraf Abstract The plant hormone gibberellin (GA) impacts plant growth and development differently depending on the developmental context. In the maize (Zea mays) tassel, application of GA alters floral development, resulting in the persistence of pistils. GA signaling is achieved by the GA-dependent turnover of DELLA domain transcription factors, encoded by dwarf8 (d8) and dwarf9 (d9) in maize. The D8-Mpl and D9-1 alleles disrupt GA signaling, resulting in short plants and normal tassel floret development in the presence of excess GA. However, D9-1 mutants are unable to block GA-induced pistil development. Gene expression in developing tassels of D8-Mpl and D9-1 mutants and their wild-type siblings was determined upon excess GA3 and mock treatments. Using GA-sensitive transcripts as reporters of GA signaling, we identified a weak loss of repression under mock conditions in both mutants, with the effect in D9-1 being greater. D9-1 was also less able to repress GA signaling in the presence of excess GA3. We treated a diverse set of maize inbred lines with excess GA3 and measured the phenotypic consequences on multiple aspects of development (e.g., height and pistil persistence in tassel florets). Genotype affected all GA-regulated phenotypes but there was no correlation between any of the GA-affected phenotypes, indicating that the complexity of the relationship between GA and development extends beyond the two-gene epistasis previously demonstrated for GA and brassinosteroid biosynthetic mutants. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: A single-cell Arabidopsis root atlas reveals developmental trajectories in wild-type and cell identity mutants Journal: Developmental Cell Year: 2022 Guest: Rachel Shahan Host: Arif Ashraf Abstract In all multicellular organisms, transcriptional networks orchestrate organ development. The Arabidopsis root, with its simple structure and indeterminate growth, is an ideal model for investigating the spatiotemporal transcriptional signatures underlying developmental trajectories. To map gene expression dynamics across root cell types and developmental time, we built a comprehensive, organ-scale atlas at single-cell resolution. In addition to estimating developmental progressions in pseudotime, we employed the mathematical concept of optimal transport to infer developmental trajectories and identify their underlying regulators. To demonstrate the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single-cell resolution, shortroot and scarecrow. We report transcriptomic and in vivo evidence for tissue trans-differentiation underlying a mixed cell identity phenotype in scarecrow. Our results support the atlas as a rich community resource for unraveling the transcriptional programs that specify and maintain cell identity to regulate spatiotemporal organ development. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Genome of Paspalum vaginatum and the role of trehalose mediated autophagy in increasing maize biomass Journal: Nature Communications Year: 2022 Guest: Guangchao Sun Host: Arif Ashraf Abstract A number of crop wild relatives can tolerate extreme stress to a degree outside the range observed in their domesticated relatives. However, it is unclear whether or how the molecular mechanisms employed by these species can be translated to domesticated crops. Paspalum (Paspalum vaginatum) is a self-incompatible and multiply stress-tolerant wild relative of maize and sorghum. Here, we describe the sequencing and pseudomolecule level assembly of a vegetatively propagated accession of P. vaginatum. Phylogenetic analysis based on 6,151 single-copy syntenic orthologues conserved in 6 related grass species places paspalum as an outgroup of the maize-sorghum clade. In parallel metabolic experiments, paspalum, but neither maize nor sorghum, exhibits a significant increase in trehalose when grown under nutrient-deficit conditions. Inducing trehalose accumulation in maize, imitating the metabolic phenotype of paspalum, results in autophagy dependent increases in biomass accumulation. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: The miR156 juvenility factor and PLETHORA 2 form a regulatory network and influence timing of meristem growth and lateral root emergence Journal: Development Year: 2022 Guest: Marta Laskowski Host: Arif Ashraf Abstract Plants develop throughout their lives: seeds become seedlings that mature and form fruits and seeds. Although the underlying mechanisms that drive these developmental phase transitions have been well elucidated for shoots, the extent to which they affect the root is less clear. However, root anatomy does change as some plants mature; meristems enlarge and radial thickening occurs. Here, in Arabidopsis thaliana, we show that overexpressing miR156A, a gene that promotes the juvenile phase, increased the density of the root system, even in grafted plants in which only the rootstock had the overexpression genotype. In the root, overexpression of miR156A resulted in lower levels of PLETHORA 2, a protein that affects formation of the meristem and elongation zone. Crossing in an extra copy of PLETHORA 2 partially rescued the effects of miR156A overexpression on traits affecting root architecture, including meristem length and the rate of lateral root emergence. Consistent with this, PLETHORA 2 also inhibited the root-tip expression of another miR156 gene, miR156C. We conclude that the system driving phase change in the shoot affects developmental progression in the root, and that PLETHORA 2 participates in this network. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Synthetic genetic circuits as a means of reprogramming plant roots Journal: Science Year: 2022 Guest: Jenn Brophy Host: Arif Ashraf Abstract The shape of a plant’s root system influences its ability to reach essential nutrients in the soil and to acquire water during drought. Progress in engineering plant roots to optimize water and nutrient acquisition has been limited by our capacity to design and build genetic programs that alter root growth in a predictable manner. We developed a collection of synthetic transcriptional regulators for plants that can be compiled to create genetic circuits. These circuits control gene expression by performing Boolean logic operations and can be used to predictably alter root structure. This work demonstrates the potential of synthetic genetic circuits to control gene expression across tissues and reprogram plant growth. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: CAN OF SPINACH, a novel long non-coding RNA, affects iron deficiency responses in Arabidopsis thaliana Journal: Frontiers in Plant Science Year: 2022 Guest: Ahmet Bakirbas Host: Arif Ashraf Abstract Long non-coding RNAs (lncRNAs) are RNA molecules with functions independent of any protein-coding potential. A whole transcriptome (RNA-seq) study of Arabidopsis shoots under iron sufficient and deficient conditions was carried out to determine the genes that are iron-regulated in the shoots. We identified two previously unannotated transcripts on chromosome 1 that are significantly iron-regulated. We have called this iron-regulated lncRNA, CAN OF SPINACH (COS). cos mutants have altered iron levels in leaves and seeds. Despite the low iron levels in the leaves, cos mutants have higher chlorophyll levels than WT plants. Moreover, cos mutants have abnormal development during iron deficiency. Roots of cos mutants are longer than those of WT plants, when grown on iron deficient medium. In addition, cos mutant plants accumulate singlet oxygen during iron deficiency. The mechanism through which COS affects iron deficiency responses is unclear, but small regions of sequence similarity to several genes involved in iron deficiency responses occur in COS, and small RNAs from these regions have been detected. We hypothesize that COS is required for normal adaptation to iron deficiency conditions. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Alternative photosynthesis pathways drive the algal CO2-concentrating mechanism Journal: Nature Year: 2022 Guest: Adrien Burlacot Host: Arif Ashraf Abstract Global photosynthesis consumes ten times more CO2 than net anthropogenic emissions, and microalgae account for nearly half of this consumption. The high efficiency of algal photosynthesis relies on a mechanism concentrating CO2 (CCM) at the catalytic site of the carboxylating enzyme RuBisCO, which enhances CO2 fixation. Although many cellular components involved in the transport and sequestration of inorganic carbon have been identified how microalgae supply energy to concentrate CO2 against a thermodynamic gradient remains unknown. Here we show that in the green alga Chlamydomonas reinhardtii, the combined action of cyclic electron flow and O2 photoreduction—which depend on PGRL1 and flavodiiron proteins, respectively—generate a low luminal pH that is essential for CCM function. We suggest that luminal protons are used downstream of thylakoid bestrophin-like transporters, probably for the conversion of bicarbonate to CO2. We further establish that an electron flow from chloroplast to mitochondria contributes to energizing non-thylakoid inorganic carbon transporters, probably by supplying ATP. We propose an integrated view of the network supplying energy to the CCM, and describe how algal cells distribute energy from photosynthesis to power different CCM processes. These results suggest a route for the transfer of a functional algal CCM to plants to improve crop productivity. Art credit: Solène Moulin Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Oxygen uptake rates have contrasting responses to temperature in the root meristem and elongation zone Journal: Physiologia Plantarum Year: 2022 Guest: Maura Zimmermann Host: Arif Ashraf Abstract Growing at either 15 or 25°C, roots of Arabidopsis thaliana, Columbia accession, produce cells at the same rate and have growth zones of the same length. To determine whether this constancy is related to energetics, we measured oxygen uptake by means of a vibrating oxygen-selective electrode. Concomitantly, the spatial distribution of elongation was measured kinematically, delineating meristem and elongation zone. All seedlings were germinated, grown, and measured at a given temperature (15 or 25°C). Columbia was compared to lines where cell production rate roughly doubles between 15 and 25°C: Landsberg and two Columbia mutants, er-105 and ahk3-3. For all genotypes and temperatures, oxygen uptake rate at any position was highest at the root cap, where mitochondrial density was maximal, based on the fluorescence of a reporter. Uptake rate declined through the meristem to plateau within the elongation zone. For oxygen uptake rate integrated over a zone, the meristem had steady-state Q10 values ranging from 0.7 to 2.1; by contrast, the elongation zone had values ranging from 2.6 to 3.3, implying that this zone exerts a greater respiratory demand. These results highlight a substantial energy consumption by the root cap, perhaps helpful for maintaining hypoxia in stem cells, and suggest that rapid elongation is metabolically more costly than is cell division. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Distinct mechanisms orchestrate the contra-polarity of IRK and KOIN, two LRR-receptor-kinases controlling root cell division Journal: Nature Communications Year: 2022 Guest: Cecilia Rodriguez-Furlan Host: Arif Ashraf Abstract In plants, cell polarity plays key roles in coordinating developmental processes. Despite the characterization of several polarly localized plasma membrane proteins, the mechanisms connecting protein dynamics with cellular functions often remain unclear. Here, we introduce a polarized receptor, KOIN, that restricts cell divisions in the Arabidopsis root meristem. In the endodermis, KOIN polarity is opposite to IRK, a receptor that represses endodermal cell divisions. Their contra-polar localization facilitates dissection of polarity mechanisms and the links between polarity and function. We find that IRK and KOIN are recognized, sorted, and secreted through distinct pathways. IRK extracellular domains determine its polarity and partially rescue the mutant phenotype, whereas KOIN’s extracellular domains are insufficient for polar sorting and function. Endodermal expression of an IRK/KOIN chimera generates non-cell-autonomous misregulation of root cell divisions that impacts patterning. Altogether, we reveal two contrasting mechanisms determining these receptors’ polarity and link their polarity to cell divisions in root tissue patterning. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Spatial control of potato tuberization by the TCP transcription factor BRANCHED1b Journal: Nature Plants Year: 2022 Guest: Michael Nicolas Host: Arif Ashraf Abstract The control of carbon allocation, storage and usage is critical for plant growth and development and is exploited for both crop food production and CO2 capture. Potato tubers are natural carbon reserves in the form of starch that have evolved to allow propagation and survival over winter. They form from stolons, below ground, where they are protected from adverse environmental conditions and animal foraging. We show that BRANCHED1b (BRC1b) acts as a tuberization repressor in aerial axillary buds, which prevents buds from competing in sink strength with stolons. BRC1b loss of function leads to ectopic production of aerial tubers and reduced underground tuberization. In aerial axillary buds, BRC1b promotes dormancy, abscisic acid responses and a reduced number of plasmodesmata. This limits sucrose accumulation and access of the tuberigen protein SP6A. BRC1b also directly interacts with SP6A and blocks its tuber-inducing activity in aerial nodes. Altogether, these actions help promote tuberization underground. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Cytokinin–CLAVATA cross-talk is an ancient mechanism regulating shoot meristem homeostasis in land plants Journal: PNAS Year: 2022 Guest: Joseph Cammarata Host: Arif Ashraf Abstract Plant shoots grow from stem cells within shoot apical meristems (SAMs), which produce lateral organs while maintaining the stem cell pool. In the model flowering plant Arabidopsis, the CLAVATA (CLV) pathway functions antagonistically with cytokinin signaling to control the size of the multicellular SAM via negative regulation of the stem cell organizer WUSCHEL (WUS). Although comprising just a single cell, the SAM of the model moss Physcomitrium patens (formerly Physcomitrella patens) performs equivalent functions during stem cell maintenance and organogenesis, despite the absence of WUS-mediated stem cell organization. Our previous work showed that the stem cell–delimiting function of the receptors CLAVATA1 (CLV1) and RECEPTOR-LIKE PROTEIN KINASE2 (RPK2) is conserved in the moss P. patens. Here, we use P. patens to assess whether CLV–cytokinin cross-talk is also an evolutionarily conserved feature of stem cell regulation. Application of cytokinin produces ectopic stem cell phenotypes similar to Ppclv1a, Ppclv1b, and Pprpk2 mutants. Surprisingly, cytokinin receptor mutants also form ectopic stem cells in the absence of cytokinin signaling. Through modeling, we identified regulatory network architectures that recapitulated the stem cell phenotypes of Ppclv1a, Ppclv1b, and Pprpk2 mutants, cytokinin application, cytokinin receptor mutations, and higher-order combinations of these perturbations. These models predict that PpCLV1 and PpRPK2 act through separate pathways wherein PpCLV1 represses cytokinin-mediated stem cell initiation, and PpRPK2 inhibits this process via a separate, cytokinin-independent pathway. Our analysis suggests that cross-talk between CLV1 and cytokinin signaling is an evolutionarily conserved feature of SAM homeostasis that preceded the role of WUS in stem cell organization. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Multiple brace root phenotypes promote anchorage and limit root lodging in maize Journal: Plant, Cell & Environment Year: 2022 Guest: Ashley Hostetler Host: Arif Ashraf Abstract Plant mechanical failure (lodging) causes global yield losses of 7%−66% in cereal crops. We have previously shown that the above-ground nodal roots (brace roots) in maize are critical for anchorage. However, it is unknown how brace root phenotypes vary across genotypes and the functional consequence of this variation. This study quantifies the contribution of brace roots to anchorage, brace root traits, plant height, and root lodging susceptibility in 52 maize inbred lines. We show that the contribution of brace roots to anchorage and root lodging susceptibility varies among genotypes and this contribution can be explained by plant architectural variation. Additionally, supervised machine learning models were developed and show that multiple plant architectural phenotypes can predict the contribution of brace roots to anchorage and root lodging susceptibility. Together these data define the plant architectures that are important in lodging resistance and show that the contribution of brace roots to anchorage is a good proxy for root lodging susceptibility. Cover art design and audio editing: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Spatial control of cell division by GA-OsGRF7/8 module in a leaf explaining the leaf length variation between cultivated and wild rice Journal: New Phytologist Year: 2022 Guest: Vikram Jathar Host: Arif Ashraf Abstract Cellular and genetic understanding of the rice leaf size regulation is limited, despite rice being the staple food of more than half of the global population. We investigated the mechanism controlling the rice leaf length using cultivated and wild rice accessions that remarkably differed for leaf size. Comparative transcriptomics, gibberellic acid (GA) quantification and leaf kinematics of the contrasting accessions suggested the involvement of GA, cell cycle and growth-regulating factors (GRFs) in the rice leaf size regulation. Zone-specific expression analysis and VIGS established the functions of specific GRFs in the process. The leaf length of the selected accessions was strongly correlated with GA levels. Higher GA content in wild rice accessions with longer leaves and GA-induced increase in the leaf length via an increase in cell division confirmed a GA-mediated regulation of division zone in rice. Downstream to GA, OsGRF7 and OsGRF8 function for controlling cell division to determine the rice leaf length. Spatial control of cell division to determine the division zone size mediated by GA and downstream OsGRF7 and OsGRF8 explains the leaf length differences between the cultivated and wild rice. This mechanism to control the rice leaf length might have contributed to optimizing leaf size during domestication. Cover art design: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Quantitative live imaging of floral organ initiation and floral meristem termination in Aquilegia Journal: Development Year: 2022 Guest: Min Ya & Stephanie Conway Host: Arif Ashraf Abstract In-depth investigation of any developmental process in plants requires knowledge of both the underpinning molecular networks and how they directly determine patterns of cell division and expansion over time. Floral meristems (FMs) produce floral organs, after which they undergo floral meristem termination (FMT); precise control of organ initiation and FMT is crucial to the reproductive success of any flowering plant. Using live confocal imaging, we characterized developmental dynamics during floral organ primordia initiation and FMT in Aquilegia coerulea (Ranunculaceae). Our results uncover distinct patterns of primordium initiation between stamens and staminodes compared with carpels, and provide insight into the process of FMT, which is discernable based on cell division dynamics that precede carpel initiation. To our knowledge, this is the first quantitative live imaging of meristem development in a system with numerous whorls of floral organs, as well as an apocarpous gynoecium. This study provides crucial information for our understanding of how the spatial-temporal regulation of floral meristem behavior is achieved in both evolutionary and developmental contexts. Cover art design: Ragib Anjum --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Article: Mutation bias reflects natural selection in Arabidopsis thaliana Journal: Nature Year: 2022 Guest: Grey Monroe Host: Arif Ashraf Grey Monroes' tweetorial on this article: https://twitter.com/Grey_Monroe/status/1481298489191837701 Abstract Since the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences1. Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome—mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias2 reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution. --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message