An intermediate grade of finished genomic sequence suitable for comparative analyses

Blakesley, Robert W.; Hansen, Nancy F.; Mullikin, James C.; Thomas, Pamela J.; McDowell, Jennifer C.; Maskeri, Baishali; Young, Alice; Benjamin, B.; Brooks, Shelise; Coleman, Bradley I.; Gupta, Jyoti; Ho, Shi-ling; Karlins, Eric; Maduro, Quino; Stantripop, Sirintorn; Tsurgeon, C.; Vogt, Jennifer; Walker, Michelle; Masiello, Catherine A.; Guan, Xiaobin; Program, Nisc Comparative Sequencing; Bouffard, Gerard G.; Green, Eric D.

doi:10.1101/gr.2648404

Cited by 73 publications

(63 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1; Supplemental Table S1). For 14 mammals, a total of 206 Mb of sequence was obtained from mapped bacterial artificial chromosomes (BACs) and finished to "comparativegrade" standards (Blakesley et al 2004) specifically for these studies; for another 14 species, a total of 340 Mb of sequence was obtained from genome-wide sequencing efforts at varying levels of completeness and quality (Aparicio et al 2002 …”

Section: Resultsmentioning

confidence: 99%

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Margulies¹,

Cooper²,

Asimenos³

et al. 2007

Genome Res.

Self Cite

191

224

View full text Add to dashboard Cite

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.

show abstract

Section: Resultsmentioning

confidence: 99%

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Margulies¹,

Cooper²,

Asimenos³

et al. 2007

Genome Res.

Self Cite

191

224

View full text Add to dashboard Cite

show abstract

“…Future efforts are needed to determine whether the evolution of this locus is a genomic oddity or is, in fact, representative of a discrete fraction of other evolutionary breakpoints and/or ''recent'' segmental duplications. (42,43) as part of the EN-CODE project (44). An unordered and oriented BAC-based assembly was also generated for the colobus monkey (Colobus guereza).…”

Section: Discussionmentioning

confidence: 99%

A recurrent inversion on the eutherian X chromosome

Cáceres

Sullivan

Thomas

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Chromosomal inversions have an important role in evolution, and an increasing number of inversion polymorphisms are being identified in the human population. The evolutionary history of these inversions and the mechanisms by which they arise are therefore of significant interest. Previously, a polymorphic inversion on human chromosome Xq28 that includes the FLNA and EMD loci was discovered and hypothesized to have been the result of nonallelic homologous recombination (NAHR) between near-identical inverted duplications flanking this region. Here, we carried out an in-depth study of the orthologous region in 27 additional eutherians and report that this inversion is not specific to humans, but has occurred independently and repeatedly at least 10 times in multiple eutherian lineages. Moreover, inverted duplications flank the FLNA-EMD region in all 16 species for which high-quality sequence assemblies are available. Based on detailed sequence analyses, we propose a model in which the observed inverted duplications originated from a common duplication event that predates the eutherian radiation. Subsequent gene conversion homogenized the duplications, thereby providing a continuous substrate for NAHR that led to the recurrent inversion of this segment of the genome. These results provide an extreme example in support of the evolutionary breakpoint reusage hypothesis and point out that some near-identical human segmental duplications may, in fact, have originated >100 million years ago.duplication ͉ gene conversion ͉ inversion polymorphism C hromosomal rearrangements were among the first types of genetic variation to be studied and have been proposed to play an important role in genome evolution and the phenotypic differences within and between species (1, 2). The recent availability of genomic data from multiple species has led to the unexpected discovery that structural variation, including inversions, is relatively common in the human population (3, 4), as well as between closely related species, such as human and chimpanzee (5-7). Comparisons of the positions of evolutionary breakpoints in different mammalian lineages suggest that a small fraction of the mammalian genome is particularly prone to rearrangement and constitute breakpoint ''hotspots'' that have been reused over the course of mammalian evolution (e.g., refs. 8 and 9). Therefore, a conserved property of mammalian genomes appears to be the presence of a limited number of fragile regions that commonly mediate chromosomal rearrangements. This observation contrasts with the long-held view that evolutionary breakpoints are distributed randomly across the genome (10), and there has been considerable debate pitting the random breakage model versus the fragile breakage/breakpoint reusage hypothesis (11).One mechanism known to mediate chromosomal rearrangements is nonallelic recombination between homologous sequences (NAHR). In humans, 5% of the genome is comprised of segmental duplications, which are typically defined as duplications Ͼ1 kb in length and Ͼ90% ...

show abstract

“…This suggests that well-selected brachiopods offer an excellent opportunity to glimpse or reconstruct the ancestral lophotrochozoan genome, and that complete or comparative genomic sequencing (Blakesley et al 2004) of one or more brachiopod genomes should have quite high priority. If so, the choice should fall first on a craniid and a discinid, possibly also a phoronid, rhynchonellid and terebratulid, but not on a lingulid because their infaunal habit is atypical and derived.…”

Section: Article In Pressmentioning

confidence: 99%

Molecular evidence that phoronids are a subtaxon of brachiopods (Brachiopoda: Phoronata) and that genetic divergence of metazoan phyla began long before the early Cambrian

Cohen

Weydmann

2005

Organisms Diversity & Evolution

137

113

View full text Add to dashboard Cite

Concatenated SSU (18S) and partial LSU (28S) sequences ($2 kb) from 12 ingroup taxa, comprising 2 phoronids, 2 members of each of the craniid, discinid, and lingulid inarticulate brachiopod lineages, and 4 rhynchonellate, articulate brachiopods (2 rhynchonellides, 1 terebratulide and 1 terebratellide) were aligned with homologous sequences from 6 protostome, deuterostome and sponge outgroups (3964 sites). Regions of potentially ambiguous alignment were removed, and the resulting data (3275 sites, of which 377 were parsimony-informative and 635 variable) were analysed by parsimony, and by maximum and Bayesian likelihood using objectively selected models. There was no base composition heterogeneity. Relative rate tests led to the exclusion (from most analyses) of the more distant outgroups, with retention of the closer pectinid and polyplacophoran (chiton). Parsimony and likelihood bootstrap and Bayesian clade support values were generally high, but only likelihood analyses recovered all brachiopod indicator clades designated a priori. All analyses confirmed the monophyly of (brachiopods+phoronids) and identified phoronids as the sister-group of the three inarticulate brachiopod lineages. Consequently, a revised Linnean classification is proposed in which the subphylum Linguliformea comprises three classes: Lingulata, 'Phoronata' (the phoronids), and 'Craniata' (the current subphylum Craniiformea). Divergence times of all nodes were estimated by regression from node depths in non-parametrically rate-smoothed and other chronograms, calibrated against palaeontological data, with probable errors not less than 50 My. Only three predicted brachiopod divergence times disagree with palaeontological ages by more than the probable error, and a reasonable explanation exists for at least two. Pruning long-branched ingroups made scant difference to predicted divergence time estimates. The palaeontological age calibration and the existence of Lower Cambrian fossils of both main brachiopod clades together indicate that initial genetic divergence between brachiopod and molluscan (chiton) lineages occurred well before the Lower Cambrian, suggesting that much divergence between metazoan phyla took place in the Proterozoic.

show abstract

An intermediate grade of finished genomic sequence suitable for comparative analyses

Cited by 73 publications

References 47 publications

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

A recurrent inversion on the eutherian X chromosome

Molecular evidence that phoronids are a subtaxon of brachiopods (Brachiopoda: Phoronata) and that genetic divergence of metazoan phyla began long before the early Cambrian

Contact Info

Product

Resources

About