Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Content-aware image restoration: Pushing the limits of fluorescence microscopy.

Fluorescence microscopy is a key driver of discoveries in the life sciences, with observable phenomena being limited by the optics of the microscope, the chemistry of the fluorophores, and the maximum photon exposure tolerated by the sample. These limits necessitate trade-offs between imaging speed, spatial resolution, light exposure, and imaging depth. In this work we show how content-aware image restoration based on deep learning extends the range of biological phenomena observable by microscopy. We demonstrate on eight concrete examples how microscopy images can be restored even if 60-fold fewer photons are used during acquisition, how near isotropic resolution can be achieved with up to tenfold under-sampling along the axial direction, and how tubular and granular structures smaller than the diffraction limit can be resolved at 20-times-higher frame rates compared to state-of-the-art methods. All developed image restoration methods are freely available as open source software in Python, FIJI, and KNIME

Widespread adenine N6-methylation of active genes in fungi.

N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. Here we report that abundant 6mA is associated with transcriptionally active genes in early-diverging fungal lineages. Using single-molecule long-read sequencing of 16 diverse fungal genomes, we observed that up to 2.8% of all adenines were methylated in early-diverging fungi, far exceeding levels observed in other eukaryotes and more derived fungi. 6mA occurred symmetrically at ApT dinucleotides and was concentrated in dense methylated adenine clusters surrounding the transcriptional start sites of expressed genes; its distribution was inversely correlated with that of 5-methylcytosine. Our results show a striking contrast in the genomic distributions of 6mA and 5-methylcytosine and reinforce a distinct role for 6mA as a gene-expression-associated epigenomic mark in eukaryotes

Data from: Genetic variation and structure in the neotropical tree, Manilkara zapota (L) P. Royen (Sapotaceae) used by the ancient Maya

Manilkara zapota is a tropical tree species that was used by the ancient Maya in construction of their temples and as a source for fruit. Although this has been supported by ethnographic and paleoethnobotanical data, we used genetic approaches to estimate variation and structure in modern populations of this neotropical tree species to discern if genetic patterns were consistent with earlier influences of ancient Maya management or if they could be explained by the natural history of the species. Nine microsatellite markers, consisting of seven novel markers and two markers identified in a related species, were used to characterize the genetic diversity and population genetic structure in three populations of M. zapota collected from reforested, historically urbanized ancient Maya ceremonial centers in Guatemala and Belize, from home gardens in Guatemala, and from a number of cultivars. Levels of genetic variation were slightly higher in forest populations (H O = 0.447) than in gardens (0.430) and cultivated varieties of M. zapota (0.351). We observed low but significant population substructuring (θ = 0.01) between sites 90 km apart, and minimal evidence of inbreeding. Substantial levels of genetic diversity with minimal genetic structure in M. zapota are consistent with movement of the ancient Maya as they possibly carried fruits and seedlings during immigration, but they may more likely reflect natural processes such as seed and pollen being dispersed widely throughout the tropical forest