We investigated the effect of (R,S)-dichlorprop herbicide addition to soil microcosms on the degrading indigenous microbial community by targeting multiple α-ketoglutarate-dependent (α-KG) dioxygenase-encoding genes (rdpA, sdpA and tfdA group I) at both gene and transcript level. The soil microbial community responded with high growth of potential degraders as measured by the abundance of dioxygenase-encoding genes using quantitative real-time PCR (qPCR). rdpA DNA was not detectable in unamended soil but reached over 10⁶ copies g⁻¹ soil after amendment. sdpA and tfdA were both present prior to amendment at levels of ~5 × 10⁴ and ~ 10² copies g⁻¹ soil, respectively, and both reached over 10⁵copies g⁻¹ soil. While expression of all three target genes was detected during two cycles of herbicide degradation, a time-shift occurred between maximum expression of each gene. Gene diversity by denaturing gradient gel electrophoresis (DGGE) uncovered a diversity of sdpA and tfdA genes at the DNA level while rdpA remained highly conserved. However, mRNA profiles indicated that all transcribed tfdA sequences were class III genes while rdpA transcripts shared 100% identity to rdpA of Delftia acidovorans MC1 and sdpA transcripts shared 100% identity to sdpA from Sphingomonas herbicidovorans MH. This is the first report to describe expression dynamics of multiple α-KG dioxygenase-encoding genes in the indigenous microbial community as related to degradation of a phenoxypropionate herbicide in soil.

Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.

Genomic imprinting is an epigenetic phenomenon occurring in mammals and flowering plants that causes genes to adopt a parent-of-origin-specific mode of expression. While the imprinting status of genes is well conserved in mammals, clear estimates for the degree of conservation were lacking in plants. We therefore analyzed the genome-wide imprinting status of Capsella rubella, which shared a common recent ancestor with Arabidopsis thaliana ∼10 to 14 million years ago. However, only ∼14% of maternally expressed genes (MEGs) and ∼29% of paternally expressed genes (PEGs) in C. rubella were commonly imprinted in both species, revealing that genomic imprinting is a rapidly evolving phenomenon in plants. Nevertheless, conserved PEGs exhibited signs of selection, suggesting that a subset of imprinted genes play an important functional role and are therefore maintained in plants. Like in Arabidopsis, PEGs in C. rubella are frequently associated with the presence of transposable elements that preferentially belong to helitron and MuDR families. Our data further reveal that MEGs and PEGs differ in their targeting by 24-nucleotide small RNAs and asymmetric DNA methylation, suggesting different mechanisms establishing DNA methylation at MEGs and PEGs.

There is ample support for developmental regulation of glioblastoma stem cells. To examine how cell lineage controls glioblastoma stem cell function, we present a cross-species epigenome analysis of mouse and human glioblastoma stem cells. We analyze and compare the chromatin-accessibility landscape of nine mouse glioblastoma stem cell cultures of three defined origins and 60 patient-derived glioblastoma stem cell cultures by assay for transposase-accessible chromatin using sequencing. This separates the mouse cultures according to cell of origin and identifies three human glioblastoma stem cell clusters that show overlapping characteristics with each of the mouse groups, and a distribution along an axis of proneural to mesenchymal phenotypes. The epigenetic-based human glioblastoma stem cell clusters display distinct functional properties and can separate patient survival. Cross-species analyses reveals conserved epigenetic regulation of mouse and human glioblastoma stem cells. We conclude that epigenetic control of glioblastoma stem cells primarily is dictated by developmental origin which impacts clinically relevant glioblastoma stem cell properties and patient survival.

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism 1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.

How the avian sex chromosomes first evolved from autosomes remains elusive as 100 million years (Myr) of divergence and degeneration obscure their evolutionary history. The Sylvioidea group of songbirds is interesting for understanding avian sex chromosome evolution because a chromosome fusion event ∼24 Myr ago formed "neo-sex chromosomes" consisting of an added (new) and an ancestral (old) part. Here, we report the complete female genome (ZW) of one Sylvioidea species, the great reed warbler (Acrocephalus arundinaceus). Our long-read assembly shows that the added region has been translocated to both Z and W, and while the added-Z has remained its gene order the added-W part has been heavily rearranged. Phylogenetic analyses show that recombination between the homologous added-Z and -W regions continued after the fusion event, and that recombination suppression across this region took several million years to be completed. Moreover, recombination suppression was initiated across multiple positions over the added-Z, which is not consistent with a simple linear progression starting from the fusion point. As expected following recombination suppression, the added-W show signs of degeneration including repeat accumulation and gene loss. Finally, we present evidence for non-random maintenance of slowly evolving and dosage-sensitive genes on both ancestral- and added-W, a process causing correlated evolution among orthologous genes across broad taxonomic groups, regardless of sex-linkage.