Coordination of ges-1 expression between the Caenorhabditis pharynx and intestine. (25/594)

We have previously shown that the Caenorhabditis elegans gut-specific esterase gene (Ce-ges-1) has the unusual ability to be expressed in different modules of the embryonic digestive tract (anterior pharynx, posterior pharynx, and rectum) depending on sequence elements within the Ce-ges-1 promoter. In the present paper, we analyze the expression of the ges-1 homolog (Cb-ges-1) from the related nematode Caenorhabditis briggsae and show that Cb-ges-1 also has the ability to switch expression between gut and pharynx + rectum. The control of this expression switch centres on a tandem pair of WGATAR sites in the Cb-ges-1 5'-flanking region, just as it does in Ce-ges-1. We use sequence alignments and subsequent deletions to identify a region at the 3'-end of both Ce-ges-1 and Ce-ges-1 that acts as the ges-1 cryptic pharynx enhancer whose activity is revealed by removal of the 5' WGATAR sites. This region contains a conserved binding site for PHA-4 (the C. elegans ortholog of forkhead/HNF3 alpha, beta,gamma factors), which is expressed in all cells of the developing pharynx and a subset of cells of the developing rectum. We propose a model in which the normal expression of ges-1 is controlled by the gut-specific GATA factor ELT-2. We propose that, in the pharynx (and rectum), PHA-4 is normally bound to the ges-1 3'-enhancer sequence but that the activation function of PHA-4 is kept repressed by a (presently unknown) factor binding in the vicinity of the 5' WGATAR sites. We suggest that this control circuitry is maintained in Caenorhabditis because pharyngeal expression of ges-1 is advantageous only under certain developmental or environmental conditions.  (+info)

Noncoding RNA gene detection using comparative sequence analysis. (26/594)

BACKGROUND: Noncoding RNA genes produce transcripts that exert their function without ever producing proteins. Noncoding RNA gene sequences do not have strong statistical signals, unlike protein coding genes. A reliable general purpose computational genefinder for noncoding RNA genes has been elusive. RESULTS: We describe a comparative sequence analysis algorithm for detecting novel structural RNA genes. The key idea is to test the pattern of substitutions observed in a pairwise alignment of two homologous sequences. A conserved coding region tends to show a pattern of synonymous substitutions, whereas a conserved structural RNA tends to show a pattern of compensatory mutations consistent with some base-paired secondary structure. We formalize this intuition using three probabilistic "pair-grammars": a pair stochastic context free grammar modeling alignments constrained by structural RNA evolution, a pair hidden Markov model modeling alignments constrained by coding sequence evolution, and a pair hidden Markov model modeling a null hypothesis of position-independent evolution. Given an input pairwise sequence alignment (e.g. from a BLASTN comparison of two related genomes) we classify the alignment into the coding, RNA, or null class according to the posterior probability of each class. CONCLUSIONS: We have implemented this approach as a program, QRNA, which we consider to be a prototype structural noncoding RNA genefinder. Tests suggest that this approach detects noncoding RNA genes with a fair degree of reliability.  (+info)

Analysis of similarity within 142 pairs of orthologous intergenic regions of Caenorhabditis elegans and Caenorhabditis briggsae. (27/594)

Patterns of similarity between genomes of related species reflect the distribution of selective constraint within DNA. We analyzed alignments of 142 orthologous intergenic regions of Caenorhabditis elegans and Caenorhabditis briggsae and found a mosaic pattern with regions of high similarity (phylogenetic footprints) interspersed with non-alignable sequences. Footprints cover approximately 20% of intergenic regions, often occur in clumps and are rare within 5' UTRs but common within 3' UTRs. The footprints have a higher ratio of transitions to transversions than expected at random and a higher GC content than the rest of the intergenic region. The number of footprints and the GC content of footprints within an intergenic region are higher when genes are oriented so that their 5' ends form the boundaries of the intergenic region. Overall, the patterns and characteristics identified here, along with other comparative and experimental studies, suggest that many footprints have a regulatory function, although other types of function are also possible. These conclusions may be quite general across eukaryotes, and the characteristics of conserved regulatory elements determined from genomic comparisons can be useful in prediction of regulation sites within individual DNA sequences.  (+info)

Genome evolution and developmental constraint in Caenorhabditis elegans. (28/594)

It has been hypothesized that evolutionary changes will be more frequent in later ontogeny than early ontogeny because of developmental constraint. To test this hypothesis, a genomewide examination of molecular evolution through ontogeny was carried out using comparative genomic data in Caenorhabditis elegans and Caenorhabditis briggsae. We found that the mean rate of amino acid replacement is not significantly different between genes expressed during and after embryogenesis. However, synonymous substitution rates differed significantly between these two classes. A genomewide survey of correlation between codon bias and expression level found codon bias to be significantly correlated with mRNA expression (r(s) = -0.30 and P < 10(-131)) but does not alone explain differences in dS between classes. Surprisingly, it was found that genes expressed after embryogenesis have a significantly greater number of duplicates in both the C. elegans and C. briggsae genomes (P < 10(-20) and P < 10(-13)) when compared with early-expressed and nonmodulated genes. A similarity in the distribution of duplicates of nonmodulated and early-expressed genes, as well as a disproportionately higher number of early pseudogenes, lend support to the hypothesis that this difference in duplicate number is caused by selection against gene duplicates of early-expressed genes, reflecting developmental constraint. Developmental constraint at the level of gene duplication may have important implications for macroevolutionary change.  (+info)

Levels of DNA polymorphism vary with mating system in the nematode genus caenorhabditis. (29/594)

Self-fertilizing species often harbor less genetic variation than cross-fertilizing species, and at least four different models have been proposed to explain this trend. To investigate further the relationship between mating system and genetic variation, levels of DNA sequence polymorphism were compared among three closely related species in the genus Caenorhabditis: two self-fertilizing species, Caenorhabditis elegans and C. briggsae, and one cross-fertilizing species, C. remanei. As expected, estimates of silent site nucleotide diversity were lower in the two self-fertilizing species. For the mitochondrial genome, diversity in the selfing species averaged 42% of diversity in C. remanei. Interestingly, the reduction in genetic variation was much greater for the nuclear than for the mitochondrial genome. For two nuclear genes, diversity in the selfing species averaged 6 and 13% of diversity in C. remanei. We argue that either population bottlenecks or the repeated action of natural selection, coupled with high levels of selfing, are likely to explain the observed reductions in species-wide genetic diversity.  (+info)

Fourfold faster rate of genome rearrangement in nematodes than in Drosophila. (30/594)

We compared the genome of the nematode Caenorhabditis elegans to 13% of that of Caenorhabditis briggsae, identifying 252 conserved segments along their chromosomes. We detected 517 chromosomal rearrangements, with the ratio of translocations to inversions to transpositions being approximately 1:1:2. We estimate that the species diverged 50-120 million years ago, and that since then there have been 4030 rearrangements between their whole genomes. Our estimate of the rearrangement rate, 0.4-1.0 chromosomal breakages/Mb per Myr, is at least four times that of Drosophila, which was previously reported to be the fastest rate among eukaryotes. The breakpoints of translocations are strongly associated with dispersed repeats and gene family members in the C. elegans genome.  (+info)

Haldane's rule by sexual transformation in Caenorhabditis. (31/594)

Haldane's rule in C. briggsae x C. remanei broods was caused by sexual transformation; XX and XO hybrids were female. C. briggsae and C. remanei variants that partially suppress hybrid sexual transformation were identified. Effects of variant strains were cumulative. Hence, aberrant sex determination is a reproductive isolation mechanism in Caenorhabditis.  (+info)

Multiple regulatory changes contribute to the evolution of the Caenorhabditis lin-48 ovo gene. (32/594)

Recent work points to the importance of changes in gene expression patterns in species-specific differences. Here, we investigate the evolution of the nematode lin-48 ovo gene. lin-48 is expressed in several cells in both Caenorhabditis elegans and Caenorhabditis briggsae, but acts in the excretory duct cell only in C. elegans. We find the differences result both from alterations in the cis-regulatory sequences and in proteins that mediate lin-48 expression. One factor that contributes to the species differences is the bZip protein CES-2. Our results indicate the accumulation of several regulatory changes affecting one gene can contribute to evolutionary change.  (+info)