Comparing nuclear receptors in worms, flies and humans

doi:10.1016/S0165-6147(00)01859-9

Trends in Pharmacological Sciences

Volume 22, Issue 12, 1 December 2001, Pages 611-615

https://doi.org/10.1016/S0165-6147(00)01859-9 Get rights and content

Abstract

Complete nucleotide sequences are now available for different species of the animal kingdom: Caenorhabditis elegans – a nematode, Drosophila – an insect, and humans – a mammal. Such information makes it possible to compare the set of nuclear receptors found in these organisms, and to discuss the possible reasons for the differences observed. The human genome sequencing identified few new receptors, which implies that most nuclear receptors have now been found. However, information about polymorphisms and regulating sequences, obtained through genomic sequencing, will be important for understanding receptor function and disease mechanisms. The surprisingly large number of nuclear receptors in C. elegans might have implications for the development of pharmaceuticals and the understanding of the function of these animals. By contrast, Drosophila has few nuclear receptors; however, examination of the unique nuclear receptors provides information about the function of these receptors.

Section snippets

Nuclear receptors in humans: preliminary results of genomic sequencing

The human genome is now more or less completely sequenced 2, 3, which marks a breakthrough in terms of nuclear receptor research. Recently, a preliminary version of the sequence completed by Celera was made available to large parts of the academic community, and a parallel effort has also been conducted at public research centers. From these results, it is clear that few nuclear receptors have evaded detection by conventional cloning methods, as judged from searches based on both DBD and LBD

Nuclear receptors in C. elegans and Drosophila

The small nematode C. elegans was the first multicellular organism whose genome was completely sequenced, a task that was completed in December 1998 (Ref. 8). Analysis of the sequence data provided a surprising result regarding the number of nuclear receptors in this organism. Based on similarities in the signature motif of the nuclear receptor superfamily, the DNA-binding domain, the C. elegans genome was shown to contain 270 nuclear receptors, which is more than four times the number

Why does C. elegans have so many receptors, and Drosophila so few?

An obvious question following the mapping of the genomes of one nematode and one insect is why the nuclear receptor gene family has undergone this unparalleled amplification in the nematode C. elegans. To understand the relevance of this observation one must take a closer look at the biology of C. elegans. One property that distinguishes C. elegans from both mammals and insects is the extremely large proportion of the cells of the animal that are nerve cells.

The complete organism has 959 cells,

Acknowledgements

This work was supported by grants from the Swedish Medical Research Council (No. 13X-2819) and from KaroBio AB.

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Trends in Pharmacological Sciences

Abstract

Section snippets

Nuclear receptors in humans: preliminary results of genomic sequencing

Nuclear receptors in C. elegans and Drosophila

Why does C. elegans have so many receptors, and Drosophila so few?

Acknowledgements

References (25)

Nuclear receptors in nematodes: themes and variations

Trends Genet.

Nematode genome sequence dramatically extends the nuclear receptor superfamily

Trends Pharmacol. Sci.

The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily

Cell

Dissatisfactionencodes a tailless-like nuclear receptorexpressed in a subset of CNS neurons controlling Drosophila sexual behavior

Neuron

Transcription factors 3: nuclear receptors

Protein Profile

A physicalmap of the human genome

Nature

The sequence of the human genome

Science

Complete nuclear receptor sets from the human, C. elegans and Drosophila genomes

Genome Biol.

A Pro12Ala substitutionin PPARγ2 associated with decreasedreceptor activity, lower body mass indexand improved insulin sensitivity

Nat. Genet.

A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor γ 2 is associated with combined hyperlipidaemia in obesity

Eur. J. Endocrinol.

Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects

Proc. Natl. Acad. Sci. U. S. A.

Genome sequence of the nematode C. elegans: a platform for investigating biology

Science

Cited by (45)

Covalent ligands of nuclear receptors

Revisiting the role of GCNF in embryonic development

The Vitamin D receptor: Biochemical, molecular, biological, and genomic era investigations

The vitamin D receptor: Biochemical, molecular, biological, and genomic era investigations

The effect of broccoli in diet on the cytochrome P450 activities of tilapia fish (Oreochromis niloticus) during phenol exposure

Steroid metabolism in cnidarians: Insights from Nematostella vectensis

Trends in Pharmacological Sciences

OpinionComparing nuclear receptors in worms, flies and humans

Abstract

Section snippets

Nuclear receptors in humans: preliminary results of genomic sequencing

Nuclear receptors in C. elegans and Drosophila

Why does C. elegans have so many receptors, and Drosophila so few?

Acknowledgements

Trends Genet.

Trends Pharmacol. Sci.

Cell

Neuron

Transcription factors 3: nuclear receptors

Protein Profile

A physicalmap of the human genome

Nature

The sequence of the human genome

Science

Complete nuclear receptor sets from the human, C. elegans and Drosophila genomes

Genome Biol.

A Pro12Ala substitutionin PPARγ2 associated with decreasedreceptor activity, lower body mass indexand improved insulin sensitivity

Nat. Genet.

A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor γ 2 is associated with combined hyperlipidaemia in obesity

Eur. J. Endocrinol.

Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects

Proc. Natl. Acad. Sci. U. S. A.

Genome sequence of the nematode C. elegans: a platform for investigating biology

Science

Opinion
Comparing nuclear receptors in worms, flies and humans