RESUMEN
The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
Asunto(s)
Evolución Molecular , Genoma , Genómica , Ratas Endogámicas BN/genética , Animales , Composición de Base , Centrómero/genética , Cromosomas de los Mamíferos/genética , Islas de CpG/genética , Elementos Transponibles de ADN/genética , ADN Mitocondrial/genética , Duplicación de Gen , Humanos , Intrones/genética , Masculino , Ratones , Modelos Moleculares , Mutagénesis , Polimorfismo de Nucleótido Simple/genética , Sitios de Empalme de ARN/genética , ARN no Traducido/genética , Ratas , Secuencias Reguladoras de Ácidos Nucleicos/genética , Retroelementos/genética , Análisis de Secuencia de ADN , Telómero/genéticaRESUMEN
Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis of the nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found in mouse, 48 in human. Forty-seven were found in the rat, with gaps at the locations expected for the other two. Pairwise comparisons of their distribution in rat, mouse, and human identified 11 syntenic NR gene blocks, including three small clusters of two or three closely related genes, each spanning 40 kb to 1700 kb. The exon structure of the ligand-binding domain suggests that exon shuffling has played a role in the evolution of this family. An invariant splice junction in all members of the NR family except LXRbeta suggests a functional role for the intron. The ligand-binding domains of PXR and CAR are among the most divergent in the family. Their higher nucleotide substitution rates may be related to the central role played by these two NRs in the metabolism of the foreign compounds and may have resulted from limited positive selection.