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The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics.

Stein LD, Bao Z, Blasiar D, Blumenthal T, Brent MR, Chen N, Chinwalla A, Clarke L, Clee C, Coghlan A, Coulson A, D'Eustachio P, Fitch DH, Fulton LA, Fulton RE, Griffiths-Jones S, Harris TW, Hillier LW, Kamath R, Kuwabara PE, Mardis ER, Marra MA, Miner TL, Minx P, Mullikin JC, Plumb RW, Rogers J, Schein JE, Sohrmann M, Spieth J, Stajich JE, Wei C, Willey D, Wilson RK, Durbin R, Waterston RH - PLoS Biol. (2003)

Bottom Line: To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence.Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes.In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.. lstein@cshl.org

ABSTRACT
The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

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Evolutionary Divergence across C. elegans Chromosome VEach panel corresponds to a C. elegans chromosome, and the individual tracks show different measurements of evolutionary divergence.(A) Regions of synteny (colinearity) between C. elegans and C. briggsae. White areas correspond to areas where the two genomes could not be aligned owing to divergence and are more abundant in the chromosome arms.(B) C. elegans gene density and genetic map position. Gene density is plotted as a histogram, showing a relatively uniform distribution of genes across each chromosome. The relationship of the position of genes on the genetic map to their position on the sequence is superimposed on the y-axis. Steeper slopes in this plot indicate higher rates of meiotic recombination. Inflection points in the genetic map plot reflect the division of the chromosomes into recombinationally active “arms” and recombinationally slow “centers.”(C) C. briggsae/C. elegans orthologs normalized for gene density in 100 kbp sliding windows. Prominent regions of low ortholog density are seen on chromosome arms.(D) C. elegans “orphans,” genes with no significant protein similarity in C. briggsae or the non-C. elegans portion of SwissProt. This histogram has been normalized for gene density in 100 kbp sliding windows. Spikes in orphan density seem to correlate with regions of low ortholog density.(E) C. elegans genes that mutate to lethality or are lethal in RNAi screens, in 100 kbp sliding windows normalized to overall gene density. This track shows the distribution of essential genes and demonstrates their tendency to cluster in the chromosome centers.(F) Repetitive elements, binned in 100 kbp sliding windows. Repeat-rich regions correlate with both the absence of significant syntenic coverage and ortholog-poor regions.(G) The KA/KS ratio in ortholog pairs. Lower values indicate greater levels of purifying selection.(H) The rate of KS within ortholog pairs, in 100 kbp sliding windows.
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pbio.0000045-g006: Evolutionary Divergence across C. elegans Chromosome VEach panel corresponds to a C. elegans chromosome, and the individual tracks show different measurements of evolutionary divergence.(A) Regions of synteny (colinearity) between C. elegans and C. briggsae. White areas correspond to areas where the two genomes could not be aligned owing to divergence and are more abundant in the chromosome arms.(B) C. elegans gene density and genetic map position. Gene density is plotted as a histogram, showing a relatively uniform distribution of genes across each chromosome. The relationship of the position of genes on the genetic map to their position on the sequence is superimposed on the y-axis. Steeper slopes in this plot indicate higher rates of meiotic recombination. Inflection points in the genetic map plot reflect the division of the chromosomes into recombinationally active “arms” and recombinationally slow “centers.”(C) C. briggsae/C. elegans orthologs normalized for gene density in 100 kbp sliding windows. Prominent regions of low ortholog density are seen on chromosome arms.(D) C. elegans “orphans,” genes with no significant protein similarity in C. briggsae or the non-C. elegans portion of SwissProt. This histogram has been normalized for gene density in 100 kbp sliding windows. Spikes in orphan density seem to correlate with regions of low ortholog density.(E) C. elegans genes that mutate to lethality or are lethal in RNAi screens, in 100 kbp sliding windows normalized to overall gene density. This track shows the distribution of essential genes and demonstrates their tendency to cluster in the chromosome centers.(F) Repetitive elements, binned in 100 kbp sliding windows. Repeat-rich regions correlate with both the absence of significant syntenic coverage and ortholog-poor regions.(G) The KA/KS ratio in ortholog pairs. Lower values indicate greater levels of purifying selection.(H) The rate of KS within ortholog pairs, in 100 kbp sliding windows.

Mentions: When the distribution of synteny blocks, orthologs, low-stringency orphans, and silent site substitution rate is projected onto the C. elegans sequence map, an intriguing pattern appears (Figure 6; see also Poster S1). When normalized for the distribution of genes, there is a marked increase in the frequency of orthologs in the center of the chromosomes versus in the arms (Figure 6C; 74.8 versus 53.2 orthologs per 100 genes, p < 1 × 10−12 by Welch's two sample t-test) and an increase in the frequency of “orphan” genes in the chromosome arms versus the centers (Figure 6D; 6.15 versus 3.36 orphans per 100 genes in the arms versus the central regions, p < 1 × 10−8 by t-test). This pattern is correlated with the ratio of nonsynonymous to synonymous substitutions (the KA/KS ratio) between ortholog pairs, which is higher in the chromosomal arms than in the centers (Figure 6G; mean KA/KS, 0.065 versus 0.059; p < 4.6 × 10−9 by t-test). This is due in part to elevated rates of KA on chromosome arms versus centers (mean KA, 0.138 versus 0.128; p < 7.9 × 10−5 by t-test.). Although there is considerable regional variation in the rate of silent site substitutions (the KS value), there is no significant difference in the mean or variance between chromosome arms and the central regions.


The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics.

Stein LD, Bao Z, Blasiar D, Blumenthal T, Brent MR, Chen N, Chinwalla A, Clarke L, Clee C, Coghlan A, Coulson A, D'Eustachio P, Fitch DH, Fulton LA, Fulton RE, Griffiths-Jones S, Harris TW, Hillier LW, Kamath R, Kuwabara PE, Mardis ER, Marra MA, Miner TL, Minx P, Mullikin JC, Plumb RW, Rogers J, Schein JE, Sohrmann M, Spieth J, Stajich JE, Wei C, Willey D, Wilson RK, Durbin R, Waterston RH - PLoS Biol. (2003)

Evolutionary Divergence across C. elegans Chromosome VEach panel corresponds to a C. elegans chromosome, and the individual tracks show different measurements of evolutionary divergence.(A) Regions of synteny (colinearity) between C. elegans and C. briggsae. White areas correspond to areas where the two genomes could not be aligned owing to divergence and are more abundant in the chromosome arms.(B) C. elegans gene density and genetic map position. Gene density is plotted as a histogram, showing a relatively uniform distribution of genes across each chromosome. The relationship of the position of genes on the genetic map to their position on the sequence is superimposed on the y-axis. Steeper slopes in this plot indicate higher rates of meiotic recombination. Inflection points in the genetic map plot reflect the division of the chromosomes into recombinationally active “arms” and recombinationally slow “centers.”(C) C. briggsae/C. elegans orthologs normalized for gene density in 100 kbp sliding windows. Prominent regions of low ortholog density are seen on chromosome arms.(D) C. elegans “orphans,” genes with no significant protein similarity in C. briggsae or the non-C. elegans portion of SwissProt. This histogram has been normalized for gene density in 100 kbp sliding windows. Spikes in orphan density seem to correlate with regions of low ortholog density.(E) C. elegans genes that mutate to lethality or are lethal in RNAi screens, in 100 kbp sliding windows normalized to overall gene density. This track shows the distribution of essential genes and demonstrates their tendency to cluster in the chromosome centers.(F) Repetitive elements, binned in 100 kbp sliding windows. Repeat-rich regions correlate with both the absence of significant syntenic coverage and ortholog-poor regions.(G) The KA/KS ratio in ortholog pairs. Lower values indicate greater levels of purifying selection.(H) The rate of KS within ortholog pairs, in 100 kbp sliding windows.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC261899&req=5

pbio.0000045-g006: Evolutionary Divergence across C. elegans Chromosome VEach panel corresponds to a C. elegans chromosome, and the individual tracks show different measurements of evolutionary divergence.(A) Regions of synteny (colinearity) between C. elegans and C. briggsae. White areas correspond to areas where the two genomes could not be aligned owing to divergence and are more abundant in the chromosome arms.(B) C. elegans gene density and genetic map position. Gene density is plotted as a histogram, showing a relatively uniform distribution of genes across each chromosome. The relationship of the position of genes on the genetic map to their position on the sequence is superimposed on the y-axis. Steeper slopes in this plot indicate higher rates of meiotic recombination. Inflection points in the genetic map plot reflect the division of the chromosomes into recombinationally active “arms” and recombinationally slow “centers.”(C) C. briggsae/C. elegans orthologs normalized for gene density in 100 kbp sliding windows. Prominent regions of low ortholog density are seen on chromosome arms.(D) C. elegans “orphans,” genes with no significant protein similarity in C. briggsae or the non-C. elegans portion of SwissProt. This histogram has been normalized for gene density in 100 kbp sliding windows. Spikes in orphan density seem to correlate with regions of low ortholog density.(E) C. elegans genes that mutate to lethality or are lethal in RNAi screens, in 100 kbp sliding windows normalized to overall gene density. This track shows the distribution of essential genes and demonstrates their tendency to cluster in the chromosome centers.(F) Repetitive elements, binned in 100 kbp sliding windows. Repeat-rich regions correlate with both the absence of significant syntenic coverage and ortholog-poor regions.(G) The KA/KS ratio in ortholog pairs. Lower values indicate greater levels of purifying selection.(H) The rate of KS within ortholog pairs, in 100 kbp sliding windows.
Mentions: When the distribution of synteny blocks, orthologs, low-stringency orphans, and silent site substitution rate is projected onto the C. elegans sequence map, an intriguing pattern appears (Figure 6; see also Poster S1). When normalized for the distribution of genes, there is a marked increase in the frequency of orthologs in the center of the chromosomes versus in the arms (Figure 6C; 74.8 versus 53.2 orthologs per 100 genes, p < 1 × 10−12 by Welch's two sample t-test) and an increase in the frequency of “orphan” genes in the chromosome arms versus the centers (Figure 6D; 6.15 versus 3.36 orphans per 100 genes in the arms versus the central regions, p < 1 × 10−8 by t-test). This pattern is correlated with the ratio of nonsynonymous to synonymous substitutions (the KA/KS ratio) between ortholog pairs, which is higher in the chromosomal arms than in the centers (Figure 6G; mean KA/KS, 0.065 versus 0.059; p < 4.6 × 10−9 by t-test). This is due in part to elevated rates of KA on chromosome arms versus centers (mean KA, 0.138 versus 0.128; p < 7.9 × 10−5 by t-test.). Although there is considerable regional variation in the rate of silent site substitutions (the KS value), there is no significant difference in the mean or variance between chromosome arms and the central regions.

Bottom Line: To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence.Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes.In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.. lstein@cshl.org

ABSTRACT
The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

Show MeSH
Related in: MedlinePlus