(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Eukaryota: NE > Opisthokonta: NE > Metazoa: NE > Eumetazoa: NE > Bilateria: NE > Deuterostomia: NE > Chordata: NE > Craniata: NE > Vertebrata: NE > Gnathostomata: NE > Teleostomi: NE > Euteleostomi: NE > Sarcopterygii: NE > Dipnotetrapodomorpha: NE > Tetrapoda: NE > Amniota: NE > Mammalia: NE > Theria: NE > Eutheria: NE > Boreoeutheria: NE > Euarchontoglires: NE > Glires: NE > Lagomorpha: NE > Leporidae: NE > Oryctolagus: NE > Oryctolagus cuniculus: NE
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MGSPLCVPIFLAVCILIQSSTHGQSLRPEPFGRRARVTATKKTLLETETR FLLFKDKANKGCQIRLHHADTLQECGFNSSLPLVMIVHGWSVDGLLESWI WQMVAALKSQPARPVNVGLVDWISLAHSHYAVAVRNARLVGQEVAALLQW LEESAPFSRSNVHLIGYSLGAHVAGFAGSYISGKHKIGRITGLDAAGPLF EGTSASDRLSPDDATFVDAIHTFTREHMGLSVGIKQPVGHYDFYPNGGSF QPGCHFLELYKHIAQHGLNALSQTIKCAHERSVHLFIDSLLHPSMQSTAY QCSDMDSFSQGLCLGCTKGRCNTLGYHIRQEPLSKGKRLFLVTQAQSPFR VYHYQFKIQFINQIEKPLEPTFTMSLLGTKEEMQKIPITLGEGITSNKTY SFLITLNLDIGELMVIKFKWENSAVWANVWNTVQTIIPWGIKPRNSGLIL KTIRVKAGETQQRMTFCSENMDDLQLHPTQEKNFVRCEVNPKKLKLKIK
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering approximately 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for approximately 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
We have investigated a possible mechanism for the reported low activity of hepatic lipase (HL) in the rabbit by cloning and sequencing the cDNA for rabbit HL and using the clone to quantify mRNA levels. A 1.6 kb cDNA clone was sequenced and found to encode the mature protein of 477 amino acids and 20 amino acids of the hydrophobic leader peptide. A high degree of amino acid sequence identity was demonstrated with human (81%) and rat (79%) HL. The putative active site was well conserved, and mutations reported to reduce activity in HL or lipoprotein lipase were not present in the rabbit sequence. The activity and mRNA levels were compared with those of the rat, an animal possessing relatively high HL activity. In post-heparin plasma of the rat, HL activity was nine times greater than in that of the rabbit (24.9 +/- 1.6 units per ml plasma, n = 5 vs. 2.7 +/- 0.1, n = 5, P = 0.0001). Comparison of mRNA levels was made by dot blot analysis of liver poly (A+) RNA obtained from each species and probed with either rabbit or rat HL cDNA, labeled to the same specific radioactivity. Specific HL mRNA levels were found to be nine times greater in the rat than in the rabbit (8.90 +/- 0.11 units, n = 5 vs. 1.00 +/- 0.01, n = 5, P = 0.0001). Thus, low hepatic lipase activity in the rabbit is associated with low mRNA levels, suggesting that the observed species difference in activity is due to differences in the level of mRNA.