NEW YORK (Reuters Health) - The DNA sequences of human chromosomes 13 and 19 are now elucidated in detail, two research teams report in the April issue of Nature. A third article in the same issue unveils the genome sequence of the Brown Norway rat.
Human chromosome 19 comprises 63.8 megabases (Mb), Dr. Jane Grimwood at Stanford University School of Medicine in Palo Alto, California, and her associates found. They estimate a density of 26 protein-coding gene loci per Mb. Exons cover 6.4% of the sequence, significantly higher than the genome-wide average of 1.5%.
More than one quarter of chromosome 19 genes “are members of large, well-defined, tandemly clustered gene families,” Dr. Grimwood’s group writes. Functions of these clusters include transcriptional control, olfactory reception, maintenance of pregnancy, and cytochrome p450 metabolism. Others encode tissue-specific serine proteases, which are associated with tumor progression, and HLA antigen receptors.
“These clustered sets of paralogues therefore represent a potentially rich source of genetic diversity” likely to represent “an especially dynamic evolutionary history,” the geneticists add.
Dr. Andrew Dunham, at the Wellcome Trust Sanger Institute in Hinxton, UK, and his team characterized chromosome 13, which encompasses 95.5 Mb. The gene density was lower than that of other autosomes, 6.5 genes per Mb, with exon coverage of 1.3%.
Dr. Richard A. Gibbs, at Baylor College of Medicine in Houston, Texas, led the international Rat Genome Sequencing Project Consortium, which found that at 2.75 gigabases (Gb), the rat genome is smaller than that of humans (2.9 Gb) but larger than that of the mouse (2.5 Gb).
Of more than 1000 human disease genes, 76% have 1:1 orthologues in the rat, a higher proportion than the 46% of other human genes.
“It appears that, in general, genes involved in human disease are unlikely to have diverged, or to have become duplicated, deleted or lost as psuedogenes, between rat and human,” the group writes.
About one billion nucleotide bases align orthologously to mouse and human, and contain most of the known exons and regulatory elements. The authors observed a “peculiar acceleration of some aspects of rat-specific evolution,” such as genes for olfaction, adaptive immune responses and foreign compound detoxification.
“The results of the sequencing and analysis have generated some deep insights into the evolutionary processes that have given rise to these different species,” the Consortium concludes.
Source: Nature 2004;428:493-535. [ Google search on this article ]
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