Abstract:
:Tryptophan hydroxylase 2 (TPH2) is a rate-limiting enzyme of neuronal serotonin biosynthesis. Recently, two single nucleotide polymorphisms (SNPs) at the exon 11 coding region that resulted in amino acid substitutions in the C-terminal domain have been reported to affect enzyme activity in humans and mice. We determined 175 base-pair sequences of the exon 11 region in nine primate species from all recognized lineages. All nucleotide sequence substitutions were synonymous, with the exception of one adenine (A) to guanine (G) substitution at the 1404th position in the open reading frame (ORF). This substitution leads to a glutamine (Q) to arginine (R) amino acid substitution at the 468th position within chimpanzee sequences. The frequency of the G allele was 0.24 among 66 chimpanzees. Therefore, it is a novel SNP observed in chimpanzees, and we have named these two alleles as ch468Q and ch468R, respectively. When expressed in HeLa cells, ch468R caused an approximate 20% increase in enzyme function during L-5-hydroxytryptophan (5HTP) production (P<0.001). We also surveyed the interspecies difference in enzyme activity among human, chimpanzee, and rat. Although the rat showed an identical amino acid sequence at the C-terminal region as those of human and ch468Q, the rat enzyme was more active than those of human or chimpanzee (P<0.001), indicating the importance of substitutions in other regions. Our findings on the chimpanzee SNP will be a useful genetic marker in understanding the individual difference in the serotonin-related behavior.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Hong KW,Sugawara Y,Hasegawa H,Hayasaka I,Hashimoto R,Ito S,Inoue-Murayama Mdoi
10.1016/j.neulet.2006.11.010subject
Has Abstractpub_date
2007-02-02 00:00:00pages
195-200issue
3eissn
0304-3940issn
1872-7972pii
S0304-3940(06)01185-2journal_volume
412pub_type
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