Genomics

A diterpenoid biosynthetic gene cluster (BGC) has been identified in a few species in the Lamiaceae (mint) family, but its origin and evolution remain unclear. Here, the authors report assembly of genomes of three species within the family and reveal the dynamic evolutionary trajectory of the BGC.

Any planarian fragment regenerates the missing head and tail in the proper end. Early activation of the Wnt/β-catenin signaling pathway changes the chromatin accessibility of the cells of the posterior-facing wound to regenerate a tail.

There exist challenges in quantifying the length of individual telomeres at single nucleotide resolution. Here the authors report a method to capture telomeres and accurately analyse their length in human cell lines and patient peripheral blood leukocyte samples using single-molecule real-time sequencing.

Venom is a complex trait with unresolved underlying toxin expression dynamics. Here, the authors compare expression across sea anemone species, revealing variation in dominant toxin diploid copy number across populations which generates distinct haplotypes.

DNA methylation is involved in regulatory processes throughout the animal kingdom. Here, the authors map DNA methylation in 535 vertebrates and 45 invertebrates, establishing a reference dataset for cross-species analysis and exploring epigenetic variation across vertebrate evolution.

Genomes usually contain multiple chromosomes. The paper reports on GALA, a computational framework for chromosome-based sequencing data separation and gap-free de novo assembly. It allows integration of different sources of data.

Extremophilic red algae have thrived in hot springs for more than a billion years. Here, the authors analyze chromosome-level assemblies from three red algal species, finding that horizontal gene transfer, subtelomeric gene duplication, and loss of genes or reduction in gene family size have supported key extremophilic adaptations.

The GEMINI consortium sequenced 1,000 cases of idiopathic male infertility and identified a plausible Mendelian cause in 20% of cases. The infertility genes can be grouped by expression pattern, facilitating their interpretation and follow-up.

The mutation rate at any specific position in the human genome depends on sequence context. Here, the authors develop a method for predicting mutation rates of point mutations and indels based on sequence context; the results can be used to find genes where de novo mutations cause disease and genes under strong selective constraint.

Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. Here, the authors mine an extensive genome-resolved metagenomics database and identified uncharacterized families of RNA-guided, compact nucleases.

The biosynthetic pathway of type II ganoderic acids (GAs) in Ganoderma lucidum, a traditional medicinal mushroom, is unknown. Here, the authors assemble the genome of type II GAs accumulating accession, identify CYPs involving in type II GAs biosynthesis, and achieve their production in engineered baker’s yeast.

While the genetic basis of heart failure has been explored by genetic studies, the differences between subtypes are not well understood. Here, the authors performed genetic analyses on the two major subtypes of heart failure in a large biobank with genetic and health record data, finding unique genetic architecture for each subtype.

Paspalum vaginatum is a stress tolerant wild relative of maize and sorghum. Here, the authors assemble its genome at pseudomolecule level and reveal the role of trehalose mediated autophagy in increasing maize biomass productivity under nutrient-deficit conditions.

In UK Biobank exomes, the authors identified de novo mutations in tandem repeat loci. On the population level, these tandem repeats confer large effects on several trait domains including biomarkers, anthropometrics, and tissue microstructures.

Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here the authors introduce Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data.

Despite the importance of DNA methylation, accessible and high-throughput methods to profile methylation at the single-cell level are lacking. Here, the authors present sciMETv2, a high-throughput workflow that provides high-quality single-cell methylomes in a robust and simple workflow.

REM-sleep behavior disorder often precedes Parkinson’s disease or dementia. Here, the authors perform a genome-wide association study for REM-sleep behavior disorder, and discover how it potentially affects gene expression in the brain.

Retrotransposons are mobile genetic elements normally repressed by DNA methylation in differentiated cells. Here, the authors show that DNA hypomethylation in mouse induced pluripotent stem cells allows retrotransposons to jump, but this can be blocked with a reverse transcriptase inhibitor.

Integrating heterogeneous single-cell multi-omics as well as spatially resolved transcriptomic data remains a major challenge. Here the authors report a unified single-cell data integration framework using an unbalanced optimal transport-based deep network.

Methods that analyse heterogeneity and compare tissue microenvironments using spatial omics data are challenging to develop. Here, the authors present SOTIP, a method that can perform spatial heterogeneity, spatial domain, and differential microenvironment analyses across multiple spatial omics modalities.

Ribosomal RNA genes are abundant in eukaryotic genomes and code for the universal and essential RNA components of the ribosome. This study uncovers high sequence diversity of the genes within a single species and discusses the contribution of selection in the evolution of ribosomal RNA.

The human genome harbors more than 4.5 million transposable element (TE)-derived insertions, the result of recurrent waves of invasion and internal propagation. Here they show that TEs belonging to evolutionarily recent subfamilies go on to regulate later stages of human embryonic development, notably conditioning the expression of genes involved in gastrulation and early organogenesis.

Spatial transcriptomics analyses can be affected by noise and spatial correlation across tissue locations. Here, the authors develop SpatialPCA, a spatially-aware dimensionality reduction method that explicitly models spatial correlation structures, and show its application to the analysis of healthy and tumour tissues.

Sociality has evolved repeatedly in arthropods. Tong et al. compare the genomes of 22 spider species with a range of social complexity and eight independent origins of sociality, and identify specific genetic changes associated with the evolution of sociality in spiders.

Here the authors show that transposable element-mediated rearrangements impact more than 500 kbp of an average human genome, are a source of individual variation, a substrate for evolutionary change, and can occur through diverse mechanisms.

Immune genes under selection can shed light on phenotypes contributing to survival and modern inflammatory conditions. Here, the authors prioritize adaptive disease variants in 535 risk loci for 21 inflammatory conditions and report promising SNPs for functional studies with predictions of cell context and function.

By comprehensively mapping the impact that different classes of mutations (substitutions, insertions, deletions) have on the ability of the amyloid beta peptide to nucleate amyloids, the authors identify a large set of likely pathogenic variants of amyloid beta that are specifically enriched at its polar N-terminal region.

H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is the reference sequence for this pathogen. Here, Chitale et al. present a bioinformatic pipeline for accurate assembly of bacterial genome sequences, and use it to provide important updates to the M. tuberculosis reference genome.

Evolutionary principles could help distinguish driver from passenger mutations in cancer. Here, the authors develop SEISMIC, a method to identify cancer driver genes based on their deviation from expected mutation status patterns across a cohort under neutral evolution, and find potential drivers in melanoma and other cancer types.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

Multiple sequence alignments are widely used to predict protein structure, function, and phylogeny, but are uncertain with more diverged sequences. Muscle5 generates ensembles of alternative high-accurate alignments, enabling novel confidence estimates in alignments, trees, and other inferences.

Heart failure is a major cause of cardiovascular morbidity and mortality. Here, the authors report results of a genome-wide association study meta-analysis, characterizing the role of common genetic variants in heart failure, finding overlap with common cardiovascular risk factors and imaging measures of cardiac structure/function.

How subgenome-divergent and -convergent transcription is mediated and harmonized in hexaploid common wheat genome remains unclear. Here, via characterizing the cistrome maps, the authors reveal that transposon elements with transcription factor binding ability have the potential to make the contribution.

As the throughput of single-cell RNA-seq studies increases, there is a need for tools that can make the data analysis steps more streamlined and convenient. Here, the authors develop UniverSC, a tool that unifies single-cell RNA-seq analysis workflows and also facilitates their use for non-experts.

Modification of transcribed mRNAs enables regulation of transcription but its extent in cancer cells is incompletely understood. Here, the authors analyse transcript assembly in over 1000 cancer cell lines and find unannotated transcripts are common, and are associated with drug sensitivity.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

Genome evolution of Allium genus and genomic basis underlying the pungency flavor formation remain poorly understood. Here, the authors assemble the genome of bunching onion and conduct population genetics analyses to reveal Allium genome evolution, flavor formation and domestication history.

Assessment of population vulnerability and adaptive capacity under climate change is crucial for informing conservation strategies. Sang et al. assemble a reference genome for Populus koreana and combine population genomics and modelling to predict spatiotemporal responses to climate change.

Translation of 100 to 300 micropeptides from small ORFs within lncRNA was detected by Ribosomal Profiling in Drosophila embryos. These translated small ORFs showed natural selection conserving micropeptide sequence and function.

In March 2022, Aotearoa New Zealand re-opened its border allowing quarantine-free travel for many travellers. Here, the authors describe circulating Omicron sub-variants before and after the reopening of the border and show that the rate of viral introductions grew roughly linearly with the increase in daily international travel.

The Qinghai-Tibet Plateau is as cold as the Arctic, but presents unique hypoxia and high ultraviolet conditions. Here the authors find that gene flow from Arctic gyrfalcons aids plateau saker falcons’ cold adaptation, and independent non-coding genomic changes underlie hypoxic and ultraviolet responses.

Parasitoid wasps are rapidly developing as a model for evolutionary biology. Here, the authors analyze the genomes of two Anastatus wasps, revealing genomic innovations related to maintenance of genomic stability, and rapid turnover of venom genes.

Genes with moderate-low expression heritability cannot be sufficiently captured with conventional TWAS. This study introduces a new method, Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction of TWAS by using eQTL summary-level data.

Statins are promising for breast cancer therapy; dipyridamole can potentiate their effects, but is contraindicated in some cases. Here, the authors develop a pharmacogenomics pipeline to predict other compounds that potentiate statins, and validate the top candidates in cell line screens and 3D cultures.

Factors defining wheat stem rust pathogen (Pgt) virulence remain poorly characterized. Comparative population genomics based on Pgt haplotypes suggest that structural variation and admixture through somatic hybridization and sexual recombination play an important role in broadening Pgt virulence.

Plant-parasitic nematodes are a threat to crop production. Combining bioinformatics, genetic and biochemical approaches, the authors show that the plant pathogen beet cyst nematode possesses an incomplete vitamin B5 synthesis pathway, of potential prokaryotic origin, complemented by its plant host.

Genetic associations with particular patterns of brain folding may provide insight into brain development and function. Here, the authors identify and replicate 388 genetic associations with brain sulcal morphology across 40,169 UK Biobank MRI scans, revealing insights into the processes guiding cortical development and genetic correlations with neuropsychiatric phenotypes.

Endogenous retroviruses (ERV) are inherited remains of retroviruses that have colonized host genomes during evolution. Here the authors observe considerable species-specific ERV variation among Darwin’s finches, reflecting historic retrovirus-host interactions.

Here, the authors present a rare example of sympatric homoploid hybrid speciation, without ploidy changes, in the Midas cichlid fishes from Nicaragua. Midas cichlid hybrids occupy a different ecological niche, likely facilitated by body shape adaptations.