Gene remnants

Seising, E., Voss, J., Storb, U. (1984). Immunoglobulin gene remnant DNA—implications for antibody gene recombination. Nucleic Acids Res. 12,4229-4246. 

With a morphine biosynthetic gene in hand, we believed we could begin to address the question why only P. somniferum produces morphine, while other Papaver species such as P. rhoeas, P. orientale, and P. bracteatum do not. Unexpectedly, we found that the codeinone reductase transcript was present to some degree in all four species investigated. A review of the literature revealed no alkaloids reported in P. rhoeas for which codeinone reductase should participate in the synthesis. Similarly, P. orientale accumulates the alternate morphine biosynthetic precursor oripavine, but codeinone reductase is not involved in the biosynthesis of oripavine, acting instead after this alkaloid along the biosynthetic pathway to morphine.22 P. bracteatum produces the morphine precursor thebaine as a major alkaloid. As for oripavine in P. orientale, codeinone reductase would act in P. bracteatum after thebaine formation on the pathway to morphine. It appears, therefore, that the reason that P. rhoeas, P. orientale, and P. bracteatum do not produce morphine is not related to the absence of the transcript of the morphine biosynthesis-specific gene codeinone reductase. The expression of codeinone reductase may simply be an evolutionary remnant in these species. 

Mitochondria have their own limited genome, the remnants of the genome of the microorganism from which they are derived. Mitochondrial genes code for 13 proteins that are synthesized in the mitochondria and are critical parts of the mitochondrial electron transport chain. 

Actnally the human genome contains abont 600 odorant receptor genes. However, abont 250 of these are pseudogenes that have no function. They are remnants of evolution. 

Familial dysbetalipoproteinemia (type III) is characterized by the accumulation of chylomicron and VLDL remnants, which are enriched in cholesterol compared to their precursors. The primary molecular cause of familial dysbetalipoproteinemia (type III) is the homozygous presence of the apolipoprotein E2 (apoE2) isoform, which is associated with recessive inheritance of the disorder [62]. However, only 1 in 50 homozygotes for apoE2 will develop type III hyperlipoproteinemia, which is clinically characterized by palmar and tuberous xanthomas, arcus lipoides, and premature atherosclerosis of coronary, peripheral, and cerebral arteries. Precipitating factors include diabetes mellitus, renal disease, hemochromatosis, but also familial hypercholesterolemia. In addition, some rare mutations in the apoE gene have been found to cause dominant and more penetrant forms of type III hyperlipoproteinemia. 

The LDL receptor also binds to apoE and plays a significant role in the hepatic uptake of chylomicrons and VLDL remnants. However, if LDL receptors are unavailable (as, for example, in a mouse strain that lacks the gene for the LDL receptor), VLDL remnants and chylomicrons are still taken up by the liver even though LDL is not. This indicates the presence of a back-up system for receptor-mediated endocytosis of VLDL remnants and chylomicrons. One back-up receptor is lipoprotein receptor-related protein (LRP), which binds to apoE as well as to a number of other ligands. 

Effect of endocytosed cholesterol on cellular cholesterol homeostasis The chylomicron remnant-, IDL-, and LDL-derived cholesterol affects cellular cholesterol content in several ways (see Figure 18.20). First, HMG CoA reductase is inhibited by ttfi cholesterol, as a result of which, de novo cholesterol synthesis decreases. Second, synthesis of new LDL receptor protein is reduced by decreasing the expression of the LDL receptor gene, thus limiting further entry of LDL cholestrol into cells. [Note ... 

LRP is a member of the LDL receptor gene family (ref. 649) and, like the LDL receptor, performs an essential role in the removal of certain lipoprotein particles from the bloodstream. As Heeren et al. (ref. 650) explain, triglycerides are transported mainly by two distinct classes of lipoproteins, the chylomicrons and the very-low-density lipoproteins (VLDL). After assembly in the intestine, chylomicrons are carried via lymph into the bloodstream, where they are transformed at the endothelial surface to remnant lipoproteins through the catalytic action of lipoprotein lipase (for review, see ref. 651,652). After lipolysis, the lipoprotein lipase remains associated with the chylomicron remnants and, in conjunction with apolipoprotein E (apo E) (ref. 653-655), facilitates their clearance by the liver into hepatocytes (ref. 656) via LDL receptors and the LRP (ref. 657-660). (The essential role for both receptors in chylomicron remnant removal in vivo has been demonstrated in gene knockout and gene transfer experiments (ref. 661,662 for review, see ref. 663).)... 

A. Rohlmann, M. Gotthardt, R.E. Hammer and J. Herz, Inducible inactivation of hepatic LRP gene by Cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants, J. Clin. Invest. 101 (1998) 689-695. 

T.E. Willnow, Z. Sheng, S. Ishibashi and J. Herz, Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist, Science 264 (1994) 1471-1474. 

T. Hara, Y. Tan and L. Huang, In vivo gene delivery to the liver using reconstituted chylomicron remnants as a novel nonviral vector, Proc. Natl. Acad. Sci. USA 94 (1997) 14547-14552. 

A search for remnants of an RNA world in extant extremophiles that are deeply rooted in the phylogenetic tree of life. They could include RNA genes that, unlike the common retrotransposons found in eukaryotes that are just selfish genes, may have some function in the cell. The search should also include viruses from hyperther-mophilic archaeans that have already been shown, in the study at Yellowstone, to be unlike anything that has been seen before and that have characteristics of all three domains of life. 

Cocca, E., M. Ratnayake-Lecamwasam, S.A. Parker, L. Camardella, M. Ciaramella, G. di Prisco, and H.W. Detrich (1995). Genomic remnants of a-globin genes in the hemoglobinless Antarctic icefishes. Proc. Natl. Acad. Sci. USA 92 1817-1821. 

Figure 5 Proteolytic processing and signaling of the Notch receptor. In the ER, Notch is cleaved at SI by a furin-like protease to produce a stable heterodimeric receptor that is trafficked to the cell surface. Interaction with ligands such as the proteins Delta and Jagged triggers a shedding of the ectodomain by membrane-tethered metalloprotease-mediated cleavage at S2. The remnant then is cleaved at least twice, at the S3 and S4 sites, to release the Notch counterpart of Ap (Np) and the intracellular domain (NICD). The latter translocates to the nucleus where it interacts with transcription factors to influence gene expression relevant to cell differentiation.

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