Biology subjects

Lensink, M.

Publications and source records attributed to Lensink, M..

6 recordsLinked to original sources

bioRxiv2025

Delineating Mutation Bias and Selection during Plant Development

Plants accumulate germline mutations through meristematic lineages where somatic purifying selection could remove deleterious coding mutations and produce perceived mutation biases, like lower genic mutation rates. Here we describe a quantitative framework that uses mutation spectra and genome architecture to separate missing coding mutations from true genic hypomutation for selection-corrected estimates of mutation biases. In simulations of plant meristems subject to selection and mutation bias, only extremely strong dominant mutations produced gene-body patterns in the same direction as empirical estimates of hypomutation. However, after accounting for this selection, we can recover the true underlying mutation rate variation. We apply this to re-analysis of Arabidopsis mutation-accumulation datasets. After selection, we see [~]50% lower mutation rates in gene bodies and an additional [~]15-30% reduction in broadly expressed genes, consistent with mutation rate bias. This framework provides a quantitative method to compare mutation rates across the genome while explicitly controlling for selection on coding sequence mutations.

plant biology↗

bioRxiv2025

Functional Insights into Dispensable Genes using Genome-Wide Loss-of-Function Burden Tests in Arabidopsis

Not all genes are essential for plant survival. With the rise of pan-genomics, it is evident that certain genes can be lost without negatively affecting fitness. Naturally occurring loss-of-function (LoF) mutations provide a valuable perspective on gene dispensability, offering insights into deleterious and adaptive gene loss. In this study, we identified 91,751 naturally occurring LoF variants from publicly available Arabidopsis genome data. Our findings demonstrate that LoF-intolerant genes are enriched in essential biological functions and associated with specific histone marks linked to active transcription. In contrast, LoF-tolerant genes exhibit relaxed selective pressure and are enriched in functions related to pollen rejection and defense responses, and can be used as a proxy for dispensable genes in the pan-genome. Using a random forest model trained on histone marks, we achieved moderate success in predicting gene LoF tolerance, with an AUC of 0.717 in Arabidopsis and 0.768 in rice, and even across species. We also pioneered genome-wide LoF burden tests in Arabidopsis, collapsing independent LoF alleles into a single state to reduce allelic heterogeneity. By integrating LoF burden tests with transcriptomic data, we identified thousands of LoF-expression associations. Notably, this analysis accurately recapitulated the flowering time networks and identified FRIGIDA as a key regulator of flowering time genes. Furthermore, we found that collapsing alleles based on functional outcomes enhances association sensitivity. These results provide insight into gene dispensability and a framework for leveraging LoF mutations to study gene functions with improved association studies.

plant biology↗

bioRxiv2025

Triploidy is prominent in the duckweed Lemna minor complex

Duckweeds (Lemnaceae Martinov) are aquatic monocotyledonous flowering plants comprising five genera and 35 recognized species, known for being the smallest and fastest-growing flowering plants on Earth. Many species are morphologically indistinguishable due to their highly reduced structures, yet molecular evidence suggests that visually similar clones may represent distinct species or hybrids. For example, clonal accessions of the globally distributed Lemna minor in the Landolt Duckweed Collection exhibit genome size variations of several hundred megabases (Mb), raising questions about their taxonomic classification and evolutionary origins. We analyzed 58 presumed L. minor clones to resolve these relationships using a comprehensive suite of methods, including whole-genome sequencing (WGS), flow-cytometric genome size measurements, molecular markers, chromosome counting, and genomic in situ hybridization (GISH). Our findings reveal extensive genome plasticity within the "Lemna minor complex," identifying diploid and triploid L. minor clones, as well as di-haploid and triploid interspecific hybrids called L. x japonica (L. minor x L. turionifera), L. x mediterranea (L. minor x L. gibba), and a novel African-clade distinct from known L. minor lineages. Triploidy was prevalent, occurring in 29% of the clones, and was associated with enhanced growth under optimal conditions but reduced performance under high light and temperature. These findings highlight the widespread role of triploidy, cryptic species, and hybridization in the L. minor complex, emphasizing the importance of multiple approaches for accurately classifying duckweed species and understanding their evolutionary trajectories.

plant biology↗

bioRxiv2024

Convergent evolution of epigenome recruited DNA repair across the Tree of Life

Mutations fuel evolution while also causing diseases like cancer. Epigenome-targeted DNA repair can help organisms protect important genomic regions from mutation. However, the adaptive value, mechanistic diversity, and evolution of epigenome-targeted DNA repair systems across the tree of life remain unresolved. Here, we investigated the evolution of histone reader domains fused to the DNA repair protein MSH6 (MutS Homolog 6) across over 4,000 eukaryotes. We uncovered a paradigmatic example of convergent evolution: MSH6 has independently acquired distinct histone reader domains; PWWP (metazoa) and Tudor (plants), previously shown to target histone modifications in active genes in humans (H3K36me3) and Arabidopsis (H3K4me1). Conservation in MSH6 histone reader domains shows signatures of natural selection, particularly for amino acids that bind specific histone modifications. Species that have gained or retained MSH6 histone readers tend to have larger genome sizes, especially marked by significantly more introns in genic regions. These patterns support previous theoretical predictions about the co-evolution of genome architectures and mutation rate heterogeneity. The evolution of epigenome-targeted DNA repair has implications for genome evolution, health, and the mutational origins of genetic diversity across the tree of life. Short SummaryFusions between histone reader domains and the mismatch repair protein MSH6 have evolved multiple times across Eukaryotes and show evidence of selection, providing mechanistic and theoretical insight into the forces shaping genomic mutation rate heterogeneity.

evolutionary biology↗

bioRxiv2023

Epigenomic divergence underlies sequence polymorphism and the evolutionary fate of duplicate paralogs in A. thaliana.

Processes affecting rates of sequence polymorphism are fundamental to molecular evolution and the evolutionary fate of gene duplicates. The relationship between gene activity and sequence polymorphism can influence the likelihood that functionally redundant gene copies are co-maintained in stable evolutionary equilibria versus other outcomes such as neo-functionalization. Here we investigate genic variation in epigenome-associated polymorphism rates in Arabidopsis thaliana and consider whether these affect the evolution of gene duplicates. We compared the frequency of sequence polymorphism and patterns of genetic differentiation between genes classified by exon methylation patterns: unmethylated (unM), gene-body methylated (gbM), and transposon-like methylated (teM) states, which reflect divergence in gene expression. We found that the frequency of polymorphism was higher in teM (transcriptionally repressed, tissue-specific) genes and lower in gbM (active, constitutively expressed) genes. Comparisons of gene duplicates were largely consistent with genome-wide patterns - gene copies that exhibit teM tend to accumulate higher sequence polymorphism, evolve faster, and are in chromatin states associated with reduced DNA repair. This relationship between expression, the epigenome, and polymorphism may lead to the breakdown of equilibrium states that would otherwise maintain genetic redundancies. Epigenome-mediated polymorphism rate variation may therefore aid the pseudogenization of duplicate paralogs or increase the evolution of novel gene functions in duplicate paralogs maintained over evolutionary time.

genomics↗

bioRxiv2022

Differential genetic variation underlying Ammonium and Nitrate responses in Arabidopsis thaliana

Nitrogen is an essential element required for plant growth and productivity. Understanding the mechanisms and natural genetic variation underlying nitrogen use in plants will facilitate engineering plant nitrogen use to maximize crop productivity while minimizing environmental costs. To understand the scope of natural variation that may influence nitrogen use, we grew 1135 Arabidopsis thaliana natural genotypes on two nitrogen sources, nitrate and ammonium, and measured both developmental and defense metabolite traits. By using different environments and focused on multiple traits, we identified a wide array of different nitrogen responses. These responses are associated with a large number of genes, most of them not previously associated with nitrogen responses. Only a small portion of these genes appear to be shared between environments or traits while most of the detected genes are predominantly specific to a developmental or defense trait under a specific nitrogen source. Finally, by using a large population we were able to identify unique nitrogen responses, like preferring ammonium or nitrate, that appear to be generated by combinations of loci rather than a few large effect loci. This suggests that it may be possible to obtain novel phenotypes in complex nitrogen responses by manipulating sets of genes with small effects rather than solely focusing on large effect single gene manipulations. One Sentence SummaryUsing a large collection of natural genotypes, and studying both developmental and metabolic responses, we found a large number of genes that are involved in the plants nitrogen response.

plant biology↗