The UCSC Genome Browser database: 2024 update

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D1082 - D1088

Published: Nov. 11, 2023

The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide. It provides annotation on thousands of genome assemblies, ranging from human SARS-CoV2. This year, we have introduced new the Human Pangenome Reference Consortium viral genomes including We added 1,200 our GenArk system, increasing overall diversity representation. support for nine user-contributed track hubs public hub system. Additionally, released 29 tracks 11 mouse genome. Collectively, these features expand both breadth depth knowledge share publicly with

Language: Английский

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Evolutionary constraint and innovation across hundreds of placental mammals

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes 240 species, we identify bases that, when mutated, are likely affect fitness and alter disease risk. At least 332 million (~10.7%) in human genome unusually conserved across species (evolutionarily constrained) relative neutrally evolving repeats, 4552 ultraconserved elements nearly perfectly conserved. Of 101 significantly constrained single bases, 80% outside protein-coding exons half have no functional annotations Encyclopedia of DNA Elements (ENCODE) resource. Changes genes regulatory associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast imperiled biodiversity offers distinctive power identifying genetic variants function organismal phenotypes.

Language: Английский

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Leveraging base-pair mammalian constraint to understand genetic variation and human disease

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability discern which positions functionally important. Evolutionary constraint is a powerful predictor function, agnostic cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% the genome as significantly constrained and likely functional. We compared annotation, association studies, copy-number variation, clinical genetics findings, cancer data. Constrained enriched for variants that explain common heritability more than other functional annotations. Our results improve variant annotation also highlight regulatory landscape still needs be further explored linked disease.

Language: Английский

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Relating enhancer genetic variation across mammals to complex phenotypes using machine learning

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent functionally conserved despite low sequence conservation. We developed Tissue-Aware Conservation Inference Toolkit (TACIT) associate candidate with species' using predictions from machine learning models trained on specific tissues. Applying TACIT motor cortex parvalbumin-positive interneuron neurological revealed dozens enhancer-phenotype associations, including brain size-associated interact genes implicated in microcephaly or macrocephaly. provides a foundation for identifying associated evolution any convergently evolved phenotype large group aligned genomes.

Language: Английский

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Bat genomes illuminate adaptations to viral tolerance and disease resistance

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested harbour more zoonotic viruses than any other mammalian order1. Infections in bats largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, Bat1K project generated reference-quality genomes ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 that revealed signatures selection immune genes prevalent orders. We found an excess gene adaptations ancestral chiropteran branch many descending lineages, highlighting entry detection factors, regulators antiviral inflammatory responses. ISG15, which is contributing hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes rhinolophid hipposiderid bats. Cellular infection experiments show species-specific differences essential role protein conjugation function separate its secretion Furthermore, contrast humans, ISG15 most has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms contribute tolerance resistance A genomes, 10 new positive shows aid bats, coronaviruses.

Language: Английский

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Complete sequencing of ape genomes

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract The most dynamic and repetitive regions of great ape genomes have traditionally been excluded from comparative studies 1–3 . Consequently, our understanding the evolution species is incomplete. Here we present haplotype-resolved reference analyses six species: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan siamang. We achieve chromosome-level contiguity with substantial sequence accuracy (<1 error in 2.7 megabases) completely 215 gapless chromosomes telomere-to-telomere. resolve challenging regions, such as major histocompatibility complex immunoglobulin loci, to provide in-depth evolutionary insights. Comparative enabled investigations diversity previously uncharacterized or incompletely studied without bias mapping human genome. Such include newly minted gene families lineage-specific segmental duplications, centromeric DNA, acrocentric subterminal heterochromatin. This resource serves a comprehensive baseline for future humans closest living relatives.

Language: Английский

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Long-Read Sequencing Reveals Rapid Evolution of Immunity- and Cancer-Related Genes in Bats

Genome Biology and Evolution, Journal Year: 2023, Volume and Issue: 15(9)

Published: Sept. 1, 2023

Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems therefore have been of particular interest in comparative genomics. Using the Oxford Nanopore Technologies long-read platform, we sequenced genomes two bat species with key phylogenetic positions, Jamaican fruit (Artibeus jamaicensis) Mesoamerican mustached (Pteronotus mesoamericanus), carried out a comprehensive genomic analysis diverse collection bats other mammals. The high-quality, genome assemblies revealed contraction interferon (IFN)-α at immunity-related type I IFN locus bats, resulting shift relative IFN-ω IFN-α copy numbers. Contradicting previous hypotheses constitutive expression being feature system, three lost all genes. This to could contribute increased viral tolerance that has made common reservoir viruses can be transmitted humans. Antiviral genes stimulated by IFNs also showed evidence rapid evolution, including lineage-specific duplication IFN-induced transmembrane positive selection IFIT2. In addition, 33 tumor suppressors 6 DNA-repair signs selection, perhaps contributing longevity reduced cancer rates bats. rely on both bat-wide evolution gene repertoire, suggesting strategies. Our study provides new resources sheds light extraordinary molecular this critically important group

Language: Английский

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Vocal learning–associated convergent evolution in mammalian proteins and regulatory elements

Science, Journal Year: 2024, Volume and Issue: 383(6690)

Published: Feb. 29, 2024

Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (

Language: Английский

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Complete sequencing of ape genomes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran siamang. achieve chromosome-level contiguity with unparalleled sequence accuracy (<1 error in 500,000 base pairs), completely sequencing 215 gapless chromosomes telomere-to-telomere. resolve challenging regions, such as the major histocompatibility complex immunoglobulin loci, providing more in-depth evolutionary insights. Comparative analyses, including human, allow us to investigate evolution diversity regions previously uncharacterized or incompletely studied without bias from mapping human reference. This includes newly minted gene families within lineage-specific segmental duplications, centromeric DNA, acrocentric chromosomes, subterminal heterochromatin. resource should serve a definitive baseline for all future studies humans our closest living relatives.

Language: Английский

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Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3541 - 3562.e51

Published: July 1, 2024

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin a female woolly mammoth (†Mammuthus primigenius) died 52,000 years ago retained its architecture. We use PaleoHi-C map chromatin contacts assemble genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, inactive X chromosome (Xi) superdomains persist. The active compartments in more closely resemble Asian elephant than other tissues. Our analyses uncover new biology. Differences compartmentalization reveal genes whose transcription was potentially altered mammoths vs. elephants. Mammoth Xi has tetradic architecture, not bipartite like human mouse. hypothesize that, shortly after this mammoth's death, sample spontaneously freeze-dried Siberian cold, leading glass transition preserved subfossils chromosomes at nanometer scale.

Language: Английский

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