| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Aad, G., et al.
(author)
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- 2011
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swepub:Mat__t (peer-reviewed)
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| 3. |
- Cho, Nam-Hyuk, et al.
(author)
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The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host–cell interaction genes
- 2007
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:19, s. 7981-7986
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Journal article (peer-reviewed)abstract
- Scrub typhus is caused by the obligate intracellular rickettsia Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). The bacterium is maternally inherited in trombicuid mites and transmitted to humans by feeding larvae. We report here the 2,127,051-bp genome of the Boryong strain, which represents the most highly repeated bacterial genome sequenced to date. The repeat density of the scrub typhus pathogen is 200-fold higher than that of its close relative Rickettsia prowazekii, the agent of epidemic typhus. A total of 359 tra genes for components of conjugative type IV secretion systems were identified at 79 sites in the genome. Associated with these are >200 genes for signaling and host–cell interaction proteins, such as histidine kinases, ankyrin-repeat proteins, and tetratrico peptide-repeat proteins. Additionally, the O. tsutsugamushi genome contains >400 transposases, 60 phage integrases, and 70 reverse transcriptases. Deletions and rearrangements have yielded unique gene combinations as well as frequent pseudogenization in the tra clusters. A comparative analysis of the tra clusters within the genome and across strains indicates sequence homogenization by gene conversion, whereas complexity, diversity, and pseudogenization are acquired by duplications, deletions, and transposon integrations into the amplified segments. The results suggest intragenomic duplications or multiple integrations of a massively proliferating conjugative transfer system. Diversifying selection on host–cell interaction genes along with repeated population bottlenecks may drive rare genome variants to fixation, thereby short-circuiting selection for low complexity in bacterial genomes.
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| 4. |
- Simon-Lledó, Erik, et al.
(author)
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Carbonate compensation depth drives abyssal biogeography in the northeast Pacific.
- 2023
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In: Nature ecology & evolution. - 2397-334X. ; 7, s. 1388-97
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Journal article (peer-reviewed)abstract
- Abyssal seafloor communities cover more than 60% of Earth's surface. Despite their great size, abyssal plains extend across modest environmental gradients compared to other marine ecosystems. However, little is known about the patterns and processes regulating biodiversity or potentially delimiting biogeographical boundaries at regional scales in the abyss. Improved macroecological understanding of remote abyssal environments is urgent as threats of widespread anthropogenic disturbance grow in the deep ocean. Here, we use a new, basin-scale dataset to show the existence of clear regional zonation in abyssal communities across the 5,000km span of the Clarion-Clipperton Zone (northeast Pacific), an area targeted for deep-sea mining. We found two pronounced biogeographic provinces, deep and shallow-abyssal, separated by a transition zone between 4,300 and 4,800m depth. Surprisingly, species richness was maintained across this boundary by phylum-level taxonomic replacements. These regional transitions are probably related to calcium carbonate saturation boundaries as taxa dependent on calcium carbonate structures, such as shelled molluscs, appear restricted to the shallower province. Our results suggest geochemical and climatic forcing on distributions of abyssal populations over large spatial scales and provide a potential paradigm for deep-sea macroecology, opening a new basis for regional-scale biodiversity research and conservation strategies in Earth's largest biome.
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| 5. |
- Washburn, Travis, et al.
(author)
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Patterns of macrofaunal biodiversity across the Clarion-Clipperton Zone: an area targeted for seabed mining
- 2021
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
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Journal article (peer-reviewed)abstract
- Macrofauna are an abundant and diverse component of abyssal benthic communities and are likely to be heavily impacted by polymetallic nodule mining in the Clarion-Clipperton Zone (CCZ). In 2012, the International Seabed Authority (ISA) used available benthic biodiversity data and environmental proxies to establish nine no-mining areas, called Areas of Particular Environmental Interest (APEIs) in the CCZ. The APEIs were intended as a representative system of protected areas to safeguard biodiversity and ecosystem function across the region from mining impacts. Since 2012, a number of research programs have collected additional ecological baseline data from the CCZ. We assemble and analyze macrofaunal biodiversity data sets from eight studies, focusing on three dominant taxa (Polychaeta, Tanaidacea, and Isopoda), and encompassing 477 box-core samples to address the following questions: (1) How do macrofaunal abundance, biodiversity, and community structure vary across the CCZ, and what are the potential ecological drivers? (2) How representative are APEIs of the nearest contractor areas? (3) How broadly do macrofaunal species range across the CCZ region? and (4) What scientific gaps hinder our understanding of macrofaunal biodiversity and biogeography in the CCZ? Our analyses led us to hypothesize that sampling efficiencies vary across macrofaunal data sets from the CCZ, making quantitative comparisons between studies challenging. Nonetheless, we found that macrofaunal abundance and diversity varied substantially across the CCZ, likely due in part to variations in particulate organic carbon (POC) flux and nodule abundance. Most macrofaunal species were collected only as singletons or doubletons, with additional species still accumulating rapidly at all sites, and with most collected species appearing to be new to science. Thus, macrofaunal diversity remains poorly sampled and described across the CCZ, especially within APEIs, where a total of nine box cores have been taken across three APEIs. Some common macrofaunal species ranged over 600–3000 km, while other locally abundant species were collected across ≤ 200 km. The vast majority of macrofaunal species are rare, have been collected only at single sites, and may have restricted ranges. Major impediments to understanding baseline conditions of macrofaunal biodiversity across the CCZ include: (1) limited taxonomic description and/or barcoding of the diverse macrofauna, (2) inadequate sampling in most of the CCZ, especially within APEIs, and (3) lack of consistent sampling protocols and efficiencies.
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