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  • Cold Spring Harbor Laboratory  (26)
  • 1
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2001
    In:  Genome Research Vol. 11, No. 12 ( 2001-12-01), p. 1996-2008
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 11, No. 12 ( 2001-12-01), p. 1996-2008
    Abstract: Sequence database searching methods such as BLAST , are invaluable for predicting molecular function on the basis of sequence similarities among single regions of proteins. Searches of whole databases however, are not optimized to detect multiple homologous regions within a single polypeptide. Here we have used the prospero algorithm to perform self-comparisons of all predicted Drosophila melanogaster gene products. Predicted repeats, and their homologs from all species, were analyzed further to detect hitherto unappreciated evolutionary relationships. Results included the identification of novel tandem repeats in the human X-linked retinitis pigmentosa type-2 gene product, repeated segments in cystinosin, associated with a defect in cystine transport, and ‘nested’ homologous domains in dysferlin, whose gene is mutated in limb girdle muscular dystrophy. Novel signaling domain families were found that may regulate the microtubule-based cytoskeleton and ubiquitin-mediated proteolysis, respectively. Two families of glycosyl hydrolases were shown to contain internal repetitions that hint at their evolution via a piecemeal, modular approach. In addition, three examples of fruit fly genes were detected with tandem exons that appear to have arisen via internal duplication. These findings demonstrate how completely sequenced genomes can be exploited to further understand the relationships between molecular structure, function, and evolution.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2001
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 2
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 22, No. 1 ( 2012-01), p. 125-133
    Abstract: New sequencing technologies can address diverse biomedical questions but are limited by a minimum required DNA input of typically 1 μg. We describe how sequencing libraries can be reproducibly created from 20 pg of input DNA using a modified transpososome-mediated fragmentation technique. Resulting libraries incorporate in-line bar-coding, which facilitates sample multiplexes that can be sequenced using Illumina platforms with the manufacturer's sequencing primer. We demonstrate this technique by providing deep coverage sequence of the Escherichia coli K-12 genome that shows equivalent target coverage to a 1-μg input library prepared using standard Illumina methods. Reducing template quantity does, however, increase the proportion of duplicate reads and enriches coverage in low-GC regions. This finding was confirmed with exhaustive resequencing of a mouse library constructed from 20 pg of gDNA input (about seven haploid genomes) resulting in ∼0.4-fold statistical coverage of uniquely mapped fragments. This implies that a near-complete coverage of the mouse genome is obtainable with this approach using 20 genomes as input. Application of this new method now allows genomic studies from low mass samples and routine preparation of sequencing libraries from enrichment procedures.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2012
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2004
    In:  Genome Research Vol. 14, No. 4 ( 2004-04), p. 591-602
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 14, No. 4 ( 2004-04), p. 591-602
    Abstract: Chemical cues influence a range of behavioral responses in rodents. The involvement of protein odorants and odorant receptors in mediating reproductive behavior, foraging, and predator avoidance suggests that their genes may have been subject to adaptive evolution. We have estimated the consequences of selection on rodent pheromones, their receptors, and olfactory receptors. These families were chosen on the basis of multiple gene duplications since the common ancestor of rat and mouse. For each family, codons were identified that are likely to have been subject to adaptive evolution. The majority of such sites are situated on the solvent-accessible surfaces of putative pheromones and the lumenal portions of their likely receptors. We predict that these contribute to physicochemical and functional diversity within pheromone-receptor interaction sites.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2004
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 4
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 18, No. 6 ( 2008-06), p. 986-994
    Abstract: When the platypus ( Ornithorhynchus anatinus ) was first discovered, it was thought to be a taxidermist’s hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male platypuses have venomous spurs on each hind leg. The platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of platypus and reptile venom. Here we show that several venom components have evolved separately in the platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2008
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2015
    In:  Genome Research Vol. 25, No. 1 ( 2015-01), p. 1-13
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 25, No. 1 ( 2015-01), p. 1-13
    Abstract: Ninety-four percent of mammalian protein-coding exons exceed 51 nucleotides (nt) in length. The paucity of micro-exons (≤ 51 nt) suggests that their recognition and correct processing by the splicing machinery present greater challenges than for longer exons. Yet, because thousands of human genes harbor processed micro-exons, specialized mechanisms may be in place to promote their splicing. Here, we survey deep genomic data sets to define 13,085 micro-exons and to study their splicing mechanisms and molecular functions. More than 60% of annotated human micro-exons exhibit a high level of sequence conservation, an indicator of functionality. While most human micro-exons require splicing-enhancing genomic features to be processed, the splicing of hundreds of micro-exons is enhanced by the adjacent binding of splice factors in the introns of pre-messenger RNAs. Notably, splicing of a significant number of micro-exons was found to be facilitated by the binding of RBFOX proteins, which promote their inclusion in the brain, muscle, and heart. Our analyses suggest that accurate regulation of micro-exon inclusion by RBFOX proteins and PTBP1 plays an important role in the maintenance of tissue-specific protein–protein interactions.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2015
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2007
    In:  Genome Research Vol. 17, No. 7 ( 2007-07), p. 969-981
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 17, No. 7 ( 2007-07), p. 969-981
    Abstract: The newly sequenced genome of Monodelphis domestica not only provides the out-group necessary to better understand our own eutherian lineage, but it enables insights into the innovative biology of metatherians. Here, we compare Monodelphis with Homo sequences from alignments of single nucleotides, genes, and whole chromosomes. Using PhyOP, we have established orthologs in Homo for 82% (15,250) of Monodelphis gene predictions. Those with single orthologs in each species exhibited a high median synonymous substitution rate ( d S = 1.02), thereby explaining the relative paucity of aligned regions outside of coding sequences. Orthology assignments were used to construct a synteny map that illustrates the considerable fragmentation of Monodelphis and Homo karyotypes since their therian last common ancestor. Fifteen percent of Monodelphis genes are predicted, from their low divergence at synonymous sites, to have been duplicated in the metatherian lineage. The majority of Monodelphis -specific genes possess predicted roles in chemosensation, reproduction, adaptation to specific diets, and immunity. Using alignments of Monodelphis genes to sequences from either Homo or Trichosurus vulpecula (an Australian marsupial), we show that metatherian X chromosomes have elevated silent substitution rates and high G+C contents in comparison with both metatherian autosomes and eutherian chromosomes. Each of these elevations is also a feature of subtelomeric chromosomal regions. We attribute these observations to high rates of female-specific recombination near the chromosomal ends and within the X chromosome, which act to sustain or increase G+C levels by biased gene conversion. In particular, we propose that the higher G+C content of the Monodelphis X chromosome is a direct consequence of its small size relative to the giant autosomes.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2007
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2002
    In:  Genome Research Vol. 12, No. 1 ( 2002-01-01), p. 47-56
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 12, No. 1 ( 2002-01-01), p. 47-56
    Abstract: A systematic computational analysis of protein sequences containing known nuclear domains led to the identification of 28 novel domain families. This represents a 26% increase in the starting set of 107 known nuclear domain families used for the analysis. Most of the novel domains are present in all major eukaryotic lineages, but 3 are species specific. For about 500 of the 1200 proteins that contain these new domains, nuclear localization could be inferred, and for 700, additional features could be predicted. For example, we identified a new domain, likely to have a role downstream of the unfolded protein response; a nematode-specific signalling domain; and a widespread domain, likely to be a noncatalytic homolog of ubiquitin-conjugating enzymes.
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2002
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2004
    In:  Genome Research Vol. 14, No. 8 ( 2004-08), p. 1516-1529
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 14, No. 8 ( 2004-08), p. 1516-1529
    Abstract: Allelic variation within the mouse androgen-binding protein (ABP) α subunit gene ( Abpa ) has been suggested to promote assortative mating and thus prezygotic isolation. This is consistent with the elevated evolutionary rates observed for the Abpa gene, and the Abpb and Abpg genes whose products (ABPβ and ABPγ) form heterodimers with ABPα. We have investigated the mouse sequence that contains the three Abpa/b/g genes, and orthologous regions in rat, human, and chimpanzee genomes. Our studies reveal extensive “remodeling” of this region: Duplication rates of Abpa -like and Abpbg -like genes in mouse are 〉 2 orders of magnitude higher than the average rate for all mouse genes; synonymous nucleotide substitution rates are twofold higher; and the Abpabg genomic region has expanded nearly threefold since divergence of the rodents. During this time, one in six amino acid sites in ABPβγ-like proteins appear to have been subject to positive selection; these may constitute a site of interaction with receptors or ligands. Greater adaptive variation among Abpbg -like sequences than among Abpa -like sequences suggests that assortative mating preferences are more influenced by variation in Abpbg -like genes. We propose a role for ABPα/β/γ proteins as pheromones, or in modulating odorant detection. This would account for the extraordinary adaptive evolution of these genes, and surrounding genomic regions, in murid rodents.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2004
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2007
    In:  Genome Research Vol. 17, No. 5 ( 2007-05), p. 556-565
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 17, No. 5 ( 2007-05), p. 556-565
    Abstract: Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent “transcriptional noise.” Here, we describe an analysis of 3122 long and full-length, noncoding RNAs (“macroRNAs”) from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding RNAs is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the macroRNAs’ promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1%–5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these macroRNAs’ functions.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2007
    detail.hit.zdb_id: 1483456-X
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2008
    In:  Genome Research Vol. 18, No. 11 ( 2008-11), p. 1711-1723
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 18, No. 11 ( 2008-11), p. 1711-1723
    Abstract: Copy number variation is a dominant contributor to genomic variation and may frequently underlie an individual’s variable susceptibilities to disease. Here we question our previous proposition that copy number variants (CNVs) are often retained in the human population because of their adaptive benefit. We show that genic biases of CNVs are best explained, not by positive selection, but by reduced efficiency of selection in eliminating deleterious changes from the human population. Of four CNV data sets examined, three exhibit significant increases in protein evolutionary rates. These increases appear to be attributable to the frequent coincidence of CNVs with segmental duplications (SDs) that recombine infrequently. Furthermore, human orthologs of mouse genes, which, when disrupted, result in pre- or postnatal lethality, are unusually depleted in CNVs. Together, these findings support a model of reduced purifying selection (Hill–Robertson interference) within copy number variable regions that are enriched in nonessential genes, allowing both the fixation of slightly deleterious substitutions and increased drift of CNV alleles. Additionally, all four CNV sets exhibited increased rates of interspecies chromosomal rearrangement and nucleotide substitution and an increased gene density. We observe that sequences with high G+C contents are most prone to copy number variation. In particular, frequently duplicated human SD sequence, or CNVs that are large and/or observed frequently, tend to be elevated in G+C content. In contrast, SD sequences that appear fixed in the human population lie more frequently within low G+C sequence. These findings provide an overarching view of how CNVs arise and segregate in the human population.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2008
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
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