Preservation of Genes Involved in Sterol Metabolism in Cholesterol Auxotrophs: Facts and Hypotheses

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Aug 7

PMID 18682733

Citations 24

Authors

Giovanna Vinci

Xuhua Xia

Reiner A Veitia

Affiliations

Soon will be listed here.

Abstract

Background: It is known that primary sequences of enzymes involved in sterol biosynthesis are well conserved in organisms that produce sterols de novo. However, we provide evidence for a preservation of the corresponding genes in two animals unable to synthesize cholesterol (auxotrophs): Drosophila melanogaster and Caenorhabditis elegans.

Principal Findings: We have been able to detect bona fide orthologs of several ERG genes in both organisms using a series of complementary approaches. We have detected strong sequence divergence between the orthologs of the nematode and of the fruitfly; they are also very divergent with respect to the orthologs in organisms able to synthesize sterols de novo (prototrophs). Interestingly, the orthologs in both the nematode and the fruitfly are still under selective pressure. It is possible that these genes, which are not involved in cholesterol synthesis anymore, have been recruited to perform different new functions. We propose a more parsimonious way to explain their accelerated evolution and subsequent stabilization. The products of ERG genes in prototrophs might be involved in several biological roles, in addition to sterol synthesis. In the case of the nematode and the fruitfly, the relevant genes would have lost their ancestral function in cholesterogenesis but would have retained the other function(s), which keep them under pressure.

Conclusions: By exploiting microarray data we have noticed a strong expressional correlation between the orthologs of ERG24 and ERG25 in D. melanogaster and genes encoding factors involved in intracellular protein trafficking and folding and with Start1 involved in ecdysteroid synthesis. These potential functional connections are worth being explored not only in Drosophila, but also in Caenorhabditis as well as in sterol prototrophs.

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References

Schuldiner M, Collins S, Thompson N, Denic V, Bhamidipati A, Punna T . Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell. 2005; 123(3):507-19. DOI: 10.1016/j.cell.2005.08.031. View

Lees N, Skaggs B, Kirsch D, Bard M . Cloning of the late genes in the ergosterol biosynthetic pathway of Saccharomyces cerevisiae--a review. Lipids. 1995; 30(3):221-6. DOI: 10.1007/BF02537824. View

Kurzchalia T, Ward S . Why do worms need cholesterol?. Nat Cell Biol. 2003; 5(8):684-8. DOI: 10.1038/ncb0803-684. View

Eichler J, Duong F . Break on through to the other side--the Sec translocon. Trends Biochem Sci. 2004; 29(5):221-3. DOI: 10.1016/j.tibs.2004.03.001. View

Schroeder F, Woodford J, Kavecansky J, Wood W, Joiner C . Cholesterol domains in biological membranes. Mol Membr Biol. 1995; 12(1):113-9. DOI: 10.3109/09687689509038505. View

Altschul S, Madden T, Schaffer A, Zhang J, Zhang Z, Miller W . Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997; 25(17):3389-402. PMC: 146917. DOI: 10.1093/nar/25.17.3389. View

Ye Q, Callebaut I, Pezhman A, Courvalin J, Worman H . Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. J Biol Chem. 1997; 272(23):14983-9. DOI: 10.1074/jbc.272.23.14983. View

Waterham H, Koster J, Mooyer P, Noort Gv G, Kelley R, Wilcox W . Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B receptor gene. Am J Hum Genet. 2003; 72(4):1013-7. PMC: 1180330. DOI: 10.1086/373938. View

Schroeder F, Jefferson J, Kier A, Knittel J, SCALLEN T, Wood W . Membrane cholesterol dynamics: cholesterol domains and kinetic pools. Proc Soc Exp Biol Med. 1991; 196(3):235-52. DOI: 10.3181/00379727-196-43185. View

10.

Schuler E, Lin F, Worman H . Characterization of the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane. J Biol Chem. 1994; 269(15):11312-7. View

11.

Merris M, Wadsworth W, Khamrai U, Bittman R, Chitwood D, Lenard J . Sterol effects and sites of sterol accumulation in Caenorhabditis elegans: developmental requirement for 4alpha-methyl sterols. J Lipid Res. 2003; 44(1):172-81. DOI: 10.1194/jlr.m200323-jlr200. View

12.

Silve S, Dupuy P, Ferrara P, Loison G . Human lamin B receptor exhibits sterol C14-reductase activity in Saccharomyces cerevisiae. Biochim Biophys Acta. 1998; 1392(2-3):233-44. DOI: 10.1016/s0005-2760(98)00041-1. View

13.

Pamilo P, Bianchi N . Evolution of the Zfx and Zfy genes: rates and interdependence between the genes. Mol Biol Evol. 1993; 10(2):271-81. DOI: 10.1093/oxfordjournals.molbev.a040003. View

14.

Mo C, Bard M . A systematic study of yeast sterol biosynthetic protein-protein interactions using the split-ubiquitin system. Biochim Biophys Acta. 2005; 1737(2-3):152-60. DOI: 10.1016/j.bbalip.2005.11.002. View

15.

Mo C, Valachovic M, Bard M . The ERG28-encoded protein, Erg28p, interacts with both the sterol C-4 demethylation enzyme complex as well as the late biosynthetic protein, the C-24 sterol methyltransferase (Erg6p). Biochim Biophys Acta. 2004; 1686(1-2):30-6. DOI: 10.1016/j.bbalip.2004.08.001. View

16.

Yang Z, Nielsen R . Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. Mol Biol Evol. 2000; 17(1):32-43. DOI: 10.1093/oxfordjournals.molbev.a026236. View

17.

Jansen R, Greenbaum D, Gerstein M . Relating whole-genome expression data with protein-protein interactions. Genome Res. 2002; 12(1):37-46. PMC: 155252. DOI: 10.1101/gr.205602. View

18.

Claros M, von Heijne G . TopPred II: an improved software for membrane protein structure predictions. Comput Appl Biosci. 1994; 10(6):685-6. DOI: 10.1093/bioinformatics/10.6.685. View

19.

Mouritsen O, Zuckermann M . What's so special about cholesterol?. Lipids. 2005; 39(11):1101-13. DOI: 10.1007/s11745-004-1336-x. View

20.

Reimand J, Kull M, Peterson H, Hansen J, Vilo J . g:Profiler--a web-based toolset for functional profiling of gene lists from large-scale experiments. Nucleic Acids Res. 2007; 35(Web Server issue):W193-200. PMC: 1933153. DOI: 10.1093/nar/gkm226. View