Genome sequence of the Brown Norway rat yields insights into mammalian evolution

Abstract

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.

Ndufc2 Gene Inhibition Is Associated With Mitochondrial Dysfunction and Increased Stroke Susceptibility in an Animal Model of Complex Human Disease

“…Genomic DNA was prepared from liver or spleen and quality checked before sequencing on an Illumina HiSeq2000, following the manufacturer's instructions. Quality‐filtered Illumina paired‐end and/or mate pair reads were mapped to the Brown Norway reference genome, RGSC‐3.4,13 using the read alignment software Burrows‐Wheeler Aligner (BWA‐0.5.8c) 14. Genomic variants (single‐nucleotide variant and short indels [1–15 bp]) were detected using the Genome Analysis Toolkit (GATK version 1.0.6001) 15, 16.…”

Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

“…About 6,00,000 copies of L1s comprise 23% of the rat (Rattus norvegicus) genome representing the autonomous, non-LTR retrotransposons. 3 The basic structure of the reported full-length rat L1…”

“…[1][2][3] LINEs and SINEs (short interspersed nuclear elements) constitute the retrotransposons of mammalian genomes, which play a major role in genome evolution through their RNA-intermediates by a "copy and paste" mechanism. 4,5 LINEs (L1s) are non-longterminal repeat (LTR), autonomous, retrotransposons expressed as polyadenylated LINE-RNAs by RNA polymerase II and cellular transcription factors.…”

Effect of Cholesterol Enriched or Fatty-Acid Diets on Cholesterol and Lipid Levels in Young Wistar Rats

“…Rats had a compatible metabolic rate of clearance, and are physiologically close to humans, whereas mice have faster metabolic rate of clearance than humans. Additionally the rat genome is much closer to human than mice, and this genetic closeness makes the rat model more appropriate to evaluate the effects of the diet and compare it to human being [12] [13] [14]. Another advantage of this animal strain is that prolonged times consuming high cholesterol diets does not promote arteriosclerosis, allowing longer periods of treatment [15] [16].…”