Classification of common conserved sequences in mammalian intergenic regions

Abstract

Comparisons between orthologous intergenic regions of related genomes reveal numerous hits, i.e. pairs of relatively short highly similar sequences that evolved slowly, perhaps due to selective constraint. We analyzed and classified 2638 hits found within 100 pairs of complete, orthologous intergenic regions of human and murine genomes. We identified all common fragments of hits that align well with many other hits and constructed their classification. Our analysis revealed 20 abundant classes each containing 10 or more fragments. Fragments of the same class may perform the same function, e.g. bind a particular protein. Ten of the abundant classes apparently correspond to known functional consensuses, whereas others may represent novel conserved sites. Thus, large-scale comparative analysis of slowly evolving intergenic sequences can provide valuable insights into their function.

“Genome design” model: Evidence from conserved intronic sequence in human–mouse comparison

“…Previously, in a much more limited comparison of human-mouse introns (77 genes), only 23% of intron length was found to be conserved (Jareborg et al 1999). Similar figures (20%-30%) were obtained for conservation of intergenic noncoding DNA (Shabalina et al 2001;Kondrashov and Shabalina 2002). The difference for the introns arises because in the previous work (Jareborg et al 1999), an identity threshold (60%) was used, in contrast to a statistical significance threshold (P < 10…”

“…It should be noted that the identity threshold seems to be more arbitrary than the statistical significance threshold. In the work on the intergenic noncoding DNA, a threshold of 50% identity was used (Shabalina et al 2001;Kondrashov and Shabalina 2002). For the total data set studied in the present work, the identity of matched regions (found on the basis of a statistical significance threshold) was generally in the range of 51%-85% (Fig.…”

Organization and Evolution of a Gene-Rich Region of the Mouse Genome: A 12.7-Mb Region Deleted in the Del(13)Svea36H Mouse

“…The accumulating information on genome sequences from a number of species raises many questions about genome evolution. Important among these are the relative roles of whole-genome, segmental, and individual gene duplication, and the mechanisms underlying these processes (Lynch and Conery 2000; Dehal et al 2001;Eichler and Sankoff 2003;Friedman and Hughes 2004); the usefulness of inter-genome comparisons for identifying selectively conserved regions in genomes, including not only genes, but regulatory regions and functional RNA genes (Mallon et al 2000;Dehal et al 2001;Dermitzakis et al 2002;Kondrashov and Shabalina 2002;Margulies et al 2003;Frazer et al 2004); the roles of repeated (transposable element-like) and repetitive (satellites, microsatellites, and minisatellites) sequences in genome evolution (Toth et al 2000;Hancock 2002;Babcock et al 2003;Alba and Guigo 2004;Han et al 2004;Kazazian Jr. 2004); and the characteristics of sites of evolutionary chromosome breakpoints (Puttagunta et al 2000;Dehal et al 2001;Pevzner and Tesler 2003).…”

Reevaluating Human Gene Annotation: A Second-Generation Analysis of Chromosome 22

“…Finally, genomic sequence from other vertebrates enables identification of conserved sequences (Hardison et al 1997;Dubchak et al 2000;Mayor et al 2000;Korf et al 2001) that are likely to be genes. Unfortunately, the ideal combination of genomes to compare is not yet clear, and human/mouse comparisons have shown conservation outside genes (Deloukas et al 2001;Frazer et al 2001;Kondrashov and Shabalina 2002). In practice, a combination of approaches can be used to overcome the limitations of single methods, but the perfect mixture has still to be defined.…”