Evolutionary and biomedical insights from the rhesus macaque genome
Richard A. Gibbs1, Jeffrey Rogers2, Michael G. Katze3, Roger E. Bumgarner3 +174 more•Institutions (28)
13 Apr 2007-Science (American Association for the Advancement of Science)-Vol. 316, Iss: 5822, pp 222-234
TL;DR: The genome sequence of an Indian-origin Macaca mulatta female is determined and compared with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families.
Abstract: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.
4,833 citations
TL;DR: ABySS (Assembly By Short Sequences), a parallelized sequence assembler, was developed and assembled 3.5 billion paired-end reads from the genome of an African male publicly released by Illumina, Inc, representing 68% of the reference human genome.
Abstract: Widespread adoption of massively parallel deoxyribonucleic acid (DNA) sequencing instruments has prompted the recent development of de novo short read assembly algorithms. A common shortcoming of the available tools is their inability to efficiently assemble vast amounts of data generated from large-scale sequencing projects, such as the sequencing of individual human genomes to catalog natural genetic variation. To address this limitation, we developed ABySS (Assembly By Short Sequences), a parallelized sequence assembler. As a demonstration of the capability of our software, we assembled 3.5 billion paired-end reads from the genome of an African male publicly released by Illumina, Inc. Approximately 2.76 million contigs > or =100 base pairs (bp) in length were created with an N50 size of 1499 bp, representing 68% of the reference human genome. Analysis of these contigs identified polymorphic and novel sequences not present in the human reference assembly, which were validated by alignment to alternate human assemblies and to other primate genomes.
3,483 citations
Additional excerpts
...Steven J.M. Jones, and _Inancx Birol2...
[...]
TL;DR: A modified version of the Celera assembler is developed to facilitate the identification and comparison of alternate alleles within this individual diploid genome, and a novel haplotype assembly strategy is used, able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploids nature of the genome.
Abstract: Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.
1,843 citations
Max Planck Society1, Massachusetts Institute of Technology2, Harvard University3, University of California, Berkeley4, University of Washington5, Bilkent University6, Chinese Academy of Sciences7, University of California, Santa Cruz8, University of Arizona9, Russian Academy of Sciences10, Howard Hughes Medical Institute11
TL;DR: The genomic sequence provides evidence for very low rates of heterozygosity in the Denisova, probably not because of recent inbreeding, but instead because of a small population size, and illuminates the relationships between humans and archaics, including Neandertals, and establishes a catalog of genetic changes within the human lineage.
Abstract: We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of “missing evolution” in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.
1,690 citations
References
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TL;DR: The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.
Abstract: Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
35,225 citations
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
22,269 citations
28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: How BLAT was optimized is described, which is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences.
Abstract: Analyzing vertebrate genomes requires rapid mRNA/DNA and cross-species protein alignments A new tool, BLAT, is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences BLAT's speed stems from an index of all nonoverlapping K-mers in the genome This index fits inside the RAM of inexpensive computers, and need only be computed once for each genome assembly BLAT has several major stages It uses the index to find regions in the genome likely to be homologous to the query sequence It performs an alignment between homologous regions It stitches together these aligned regions (often exons) into larger alignments (typically genes) Finally, BLAT revisits small internal exons possibly missed at the first stage and adjusts large gap boundaries that have canonical splice sites where feasible This paper describes how BLAT was optimized Effects on speed and sensitivity are explored for various K-mer sizes, mismatch schemes, and number of required index matches BLAT is compared with other alignment programs on various test sets and then used in several genome-wide applications http://genomeucscedu hosts a web-based BLAT server for the human genome
8,326 citations
TL;DR: The strength of PAML, in comparison with other phylogenetic packages currently available, is its implementation of a variety of evolutionary models, which include several models of variable evolutionary rates among sites, models for combined analyses of multiple gene sequence data and models for amino acid sequences.
Abstract: PAML, currently in version 1.2, is a package of programs for phylogenetic analyses of DNA and protein sequences using the method of maximum likelihood (ML). The programs can be used for (i) maximum likelihood estimation of evolutionary parameters such as branch lengths in a phylogenetic tree, the transition/transversion rate ratio, the shape parameter of the gamma distribution for variable evolutionary rates at sites, and rate parameters for different genes; (ii) likelihood ratio test of hypotheses concerning sequence evolution, such as rate constancy and independence among sites and rate constancy among lineages (the molecular clock); (iii) calculation of substitution rates at sites and reconstruction of ancestral nucleotide or amino acid sequences; and (iv) phylogenetic tree reconstruction by maximum likelihood and Bayesian methods. The strength of PAML, in comparison with other phylogenetic packages currently available, is its implementation of a variety of evolutionary models. These include several models of variable evolutionary rates among sites, models for combined analyses of multiple gene sequence data and models for amino acid sequences. Multifurcating trees are supported, as well as trees in which some sequences are ancestral to some others. A heuristic tree search algorithm (star decomposition) is used in the package, but tree making is not a strong point of the current version, although work is under way to implement efficient search algorithms. Major programs in the package, as well as the types of analyses they perform, are listed in Table 1. More details are available in the documentation included in the package, written using Microsoft Word. PAML is distributed free of charge for academic use only. The package, including ANSI C source codes, documentation, example data sets, and control files, can be obtained by anonymous ftp at mw511.biol.berkeley.edu/pub, or from the Indiana molecular biology ftp site at ftp.bio.indiana.edu under the directory Incoming or molbio/evolve . MAC and PowerMac executables are also available, although DOS executables are not prepared yet. Further information about the package is available from the World Wide Web at
5,022 citations