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Function and evolution of the serotonin-synthetic bas-1 gene and other aromatic amino acid decarboxylase genes in Caenorhabditis.

Hare EE, Loer CM - BMC Evol. Biol. (2004)

Bottom Line: Despite their persistence in C. elegans, evidence suggests the bas-1-like genes do not encode functional AADC proteins.The presence of the genes in C. elegans raises questions about how many 'predicted genes' in sequenced genomes are functional, and how duplicate genes are retained or lost during evolution.This is another example of unexpected retention of duplicate genes in eukaryotic genomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, University of San Diego, CA 92110, USA. ehare@berkeley.edu

ABSTRACT

Background: Aromatic L-amino acid decarboxylase (AADC) enzymes catalyze the synthesis of biogenic amines, including the neurotransmitters serotonin and dopamine, throughout the animal kingdom. These neurotransmitters typically perform important functions in both the nervous system and other tissues, as illustrated by the debilitating conditions that arise from their deficiency. Studying the regulation and evolution of AADC genes is therefore desirable to further our understanding of how nervous systems function and evolve.

Results: In the nematode C. elegans, the bas-1 gene is required for both serotonin and dopamine synthesis, and maps genetically near two AADC-homologous sequences. We show by transformation rescue and sequencing of mutant alleles that bas-1 encodes an AADC enzyme. Expression of a reporter construct in transgenics suggests that the bas-1 gene is expressed, as expected, in identified serotonergic and dopaminergic neurons. The bas-1 gene is one of six AADC-like sequences in the C. elegans genome, including a duplicate that is immediately downstream of the bas-1 gene. Some of the six AADC genes are quite similar to known serotonin- and dopamine-synthetic AADC's from other organisms whereas others are divergent, suggesting previously unidentified functions. In comparing the AADC genes of C. elegans with those of the congeneric C. briggsae, we find only four orthologous AADC genes in C. briggsae. Two C. elegans AADC genes - those most similar to bas-1 - are missing from C. briggsae. Phylogenetic analysis indicates that one or both of these bas-1-like genes were present in the common ancestor of C. elegans and C. briggsae, and were retained in the C. elegans line, but lost in the C. briggsae line. Further analysis of the two bas-1-like genes in C. elegans suggests that they are unlikely to encode functional enzymes, and may be expressed pseudogenes.

Conclusions: The bas-1 gene of C. elegans encodes a serotonin- and dopamine-synthetic AADC enzyme. Two C. elegans AADC-homologous genes that are closely related to bas-1 are missing from the congeneric C. briggsae; one or more these genes was present in the common ancestor of C. elegans and C. briggsae. Despite their persistence in C. elegans, evidence suggests the bas-1-like genes do not encode functional AADC proteins. The presence of the genes in C. elegans raises questions about how many 'predicted genes' in sequenced genomes are functional, and how duplicate genes are retained or lost during evolution. This is another example of unexpected retention of duplicate genes in eukaryotic genomes.

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Serotonin and dopamine biosynthetic pathways. Serotonin and dopamine are synthesized from the aromatic amino acids tryptophan and tyrosine, respectively. The first and rate-limiting step in synthesis is carried out by a neurotransmitter-specific aromatic amino acid hydroxylase enzyme, either tryptophan or tyrosine hydroxylase. In C. elegans, these genes are encoded by the tph-1 and cat-2 genes, respectively [19, 25]. The second synthetic step for both neurotransmitters shares the aromatic L-amino acid decarboxylase (AADC) enzyme, which has a relatively broad substrate specificity, and is also known as 5-hydroxytryptophan decarboxylase or dopa decarboxylase.
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Figure 1: Serotonin and dopamine biosynthetic pathways. Serotonin and dopamine are synthesized from the aromatic amino acids tryptophan and tyrosine, respectively. The first and rate-limiting step in synthesis is carried out by a neurotransmitter-specific aromatic amino acid hydroxylase enzyme, either tryptophan or tyrosine hydroxylase. In C. elegans, these genes are encoded by the tph-1 and cat-2 genes, respectively [19, 25]. The second synthetic step for both neurotransmitters shares the aromatic L-amino acid decarboxylase (AADC) enzyme, which has a relatively broad substrate specificity, and is also known as 5-hydroxytryptophan decarboxylase or dopa decarboxylase.

Mentions: Aromatic L-amino acid decarboxylase (E.C. 4.1.1.28, AADC) catalyzes the second enzymatic step in synthesis of the neurotransmitters dopamine and serotonin, which are found in neurons of all animals (Figure 1). Alteration in the normal expression of these transmitters is associated with human neurological disorders such as Parkinson's disease and depression [1,2]. In mammals, AADC is expressed in many tissues beside the nervous system, associated with additional regulatory roles of dopamine and serotonin in a wide range of tissues [3]. In insects, AADC is further required to produce amines for cuticle synthesis and pigmentation [4]. Because of its role in the synthesis of both transmitters, by decarboxylation of L-dopa and 5-hydroxytryptophan, AADC is also known as dopa decarboxylase or 5-hydroxytryptophan decarboxylase (reviewed in [3]). AADC belongs to the α family (subgroup II) of pyridoxal-5'-phosphate (PLP) dependent enzymes. Other subgroup II enzymes include histidine, tyrosine, tryptophan and glutamate decarboxylases [5]; in animals some of these enzymes mediate synthesis of other biogenic amines (e.g., histamine, tyramine, octopamine) and GABA. In mammals and in Drosophila, a single gene encodes the serotonin- and dopamine-synthetic AADC [6,7], although tissue-specific isoforms of the protein are generated by alternative splicing [8,9]. Different genes encode PLP-dependent decarboxylase enzymes for histamine, octopamine and GABA synthesis.


Function and evolution of the serotonin-synthetic bas-1 gene and other aromatic amino acid decarboxylase genes in Caenorhabditis.

Hare EE, Loer CM - BMC Evol. Biol. (2004)

Serotonin and dopamine biosynthetic pathways. Serotonin and dopamine are synthesized from the aromatic amino acids tryptophan and tyrosine, respectively. The first and rate-limiting step in synthesis is carried out by a neurotransmitter-specific aromatic amino acid hydroxylase enzyme, either tryptophan or tyrosine hydroxylase. In C. elegans, these genes are encoded by the tph-1 and cat-2 genes, respectively [19, 25]. The second synthetic step for both neurotransmitters shares the aromatic L-amino acid decarboxylase (AADC) enzyme, which has a relatively broad substrate specificity, and is also known as 5-hydroxytryptophan decarboxylase or dopa decarboxylase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC514703&req=5

Figure 1: Serotonin and dopamine biosynthetic pathways. Serotonin and dopamine are synthesized from the aromatic amino acids tryptophan and tyrosine, respectively. The first and rate-limiting step in synthesis is carried out by a neurotransmitter-specific aromatic amino acid hydroxylase enzyme, either tryptophan or tyrosine hydroxylase. In C. elegans, these genes are encoded by the tph-1 and cat-2 genes, respectively [19, 25]. The second synthetic step for both neurotransmitters shares the aromatic L-amino acid decarboxylase (AADC) enzyme, which has a relatively broad substrate specificity, and is also known as 5-hydroxytryptophan decarboxylase or dopa decarboxylase.
Mentions: Aromatic L-amino acid decarboxylase (E.C. 4.1.1.28, AADC) catalyzes the second enzymatic step in synthesis of the neurotransmitters dopamine and serotonin, which are found in neurons of all animals (Figure 1). Alteration in the normal expression of these transmitters is associated with human neurological disorders such as Parkinson's disease and depression [1,2]. In mammals, AADC is expressed in many tissues beside the nervous system, associated with additional regulatory roles of dopamine and serotonin in a wide range of tissues [3]. In insects, AADC is further required to produce amines for cuticle synthesis and pigmentation [4]. Because of its role in the synthesis of both transmitters, by decarboxylation of L-dopa and 5-hydroxytryptophan, AADC is also known as dopa decarboxylase or 5-hydroxytryptophan decarboxylase (reviewed in [3]). AADC belongs to the α family (subgroup II) of pyridoxal-5'-phosphate (PLP) dependent enzymes. Other subgroup II enzymes include histidine, tyrosine, tryptophan and glutamate decarboxylases [5]; in animals some of these enzymes mediate synthesis of other biogenic amines (e.g., histamine, tyramine, octopamine) and GABA. In mammals and in Drosophila, a single gene encodes the serotonin- and dopamine-synthetic AADC [6,7], although tissue-specific isoforms of the protein are generated by alternative splicing [8,9]. Different genes encode PLP-dependent decarboxylase enzymes for histamine, octopamine and GABA synthesis.

Bottom Line: Despite their persistence in C. elegans, evidence suggests the bas-1-like genes do not encode functional AADC proteins.The presence of the genes in C. elegans raises questions about how many 'predicted genes' in sequenced genomes are functional, and how duplicate genes are retained or lost during evolution.This is another example of unexpected retention of duplicate genes in eukaryotic genomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, University of San Diego, CA 92110, USA. ehare@berkeley.edu

ABSTRACT

Background: Aromatic L-amino acid decarboxylase (AADC) enzymes catalyze the synthesis of biogenic amines, including the neurotransmitters serotonin and dopamine, throughout the animal kingdom. These neurotransmitters typically perform important functions in both the nervous system and other tissues, as illustrated by the debilitating conditions that arise from their deficiency. Studying the regulation and evolution of AADC genes is therefore desirable to further our understanding of how nervous systems function and evolve.

Results: In the nematode C. elegans, the bas-1 gene is required for both serotonin and dopamine synthesis, and maps genetically near two AADC-homologous sequences. We show by transformation rescue and sequencing of mutant alleles that bas-1 encodes an AADC enzyme. Expression of a reporter construct in transgenics suggests that the bas-1 gene is expressed, as expected, in identified serotonergic and dopaminergic neurons. The bas-1 gene is one of six AADC-like sequences in the C. elegans genome, including a duplicate that is immediately downstream of the bas-1 gene. Some of the six AADC genes are quite similar to known serotonin- and dopamine-synthetic AADC's from other organisms whereas others are divergent, suggesting previously unidentified functions. In comparing the AADC genes of C. elegans with those of the congeneric C. briggsae, we find only four orthologous AADC genes in C. briggsae. Two C. elegans AADC genes - those most similar to bas-1 - are missing from C. briggsae. Phylogenetic analysis indicates that one or both of these bas-1-like genes were present in the common ancestor of C. elegans and C. briggsae, and were retained in the C. elegans line, but lost in the C. briggsae line. Further analysis of the two bas-1-like genes in C. elegans suggests that they are unlikely to encode functional enzymes, and may be expressed pseudogenes.

Conclusions: The bas-1 gene of C. elegans encodes a serotonin- and dopamine-synthetic AADC enzyme. Two C. elegans AADC-homologous genes that are closely related to bas-1 are missing from the congeneric C. briggsae; one or more these genes was present in the common ancestor of C. elegans and C. briggsae. Despite their persistence in C. elegans, evidence suggests the bas-1-like genes do not encode functional AADC proteins. The presence of the genes in C. elegans raises questions about how many 'predicted genes' in sequenced genomes are functional, and how duplicate genes are retained or lost during evolution. This is another example of unexpected retention of duplicate genes in eukaryotic genomes.

Show MeSH
Related in: MedlinePlus