学術雑誌論文 An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

AKIYAMA, Tokiho  ,  KATSUMURA, Takafumi  ,  NAKAGOME, Shigeki  ,  LEE, Sang-Il  ,  JOH, Keiichiro  ,  SOEJIMA, Hidenobu  ,  FUJIMOTO, Kazuma  ,  KIMURA, Ryosuke  ,  ISHIDA, Hajime  ,  HANIHARA, Tsunehiko  ,  YASUKOUCHI, Akira  ,  SATTA, Yoko  ,  HIGUCHI, Shigekazu  ,  OOTA, Hiroki  ,  Tokiho, AKIYAMA  ,  Takafumi, KATSUMURA  ,  Shigeki, NAKAGOME  ,  Sang-Il, LEE  ,  Keiichiro, JOH  ,  Hidenobu, SOEJIMA  ,  Kazuma, FUJIMOTO  ,  Ryosuke, KIMURA  ,  Hajime, ISHIDA  ,  Tsunehiko, HANIHARA  ,  Akira, YASUKOUCHI  ,  Yoko, SATTA  ,  Shigekazu, HIGUCHI  ,  Hiroki, OOTA

12 ( 6 )  , p.e0178373 , 2017-06-26 , Public Library of Science / San Francisco, CA
ISSN:1932-6203
内容記述
Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05). The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.
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