TY - JOUR
T1 - Evolution of a length polymorphism in the human PER3 gene, a component of the circadian system
AU - Nadkarni, Nachiket A.
AU - Weale, Michael E.
AU - Von Schantz, Malcolm
AU - Thomas, Mark G.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - Period homologue 3 (PER3) is a component of the mammalian circadian system, although its precise role is unknown. A biallelic variable number tandem repeat (VNTR) polymorphism exists in human PER3, consisting of 4 or 5 repeats of a 54-bp sequence in a region encoding a putative phosphorylation domain. This polymorphism has previously been reported to associate with diurnal preference ("morningness" and "eveningness") and delayed sleep-phase syndrome. We have investigated the global allele frequencies of this variant in ethnically distinct indigenous populations. All populations were polymorphic, with the shorter (4-repeat) allele ranging in frequency from 0.19 (Papua New Guinea) to 0.89 (Mongolia). To investigate if allele frequency has been influenced by natural selection, the authors 1) tested for a correlation with latitude and mean annual insolation (incident sunlight energy), using classical markers to correct for historical population differentiation; and they 2) compared allele-frequency difference between European American, African American, and East Asian populations, as measured using FST, to an empirical null distribution of FST values based on a genome-wide dataset of single nucleotide polymorphisms (SNPs) of presumed neutral loci that were previously typed by The SNP Consortium. The variation in allele frequencies between indigenous populations did not show a pattern that would indicate selective pressure on PER3 resulting from day-length variation or mean annual insolation, and the allele-frequency difference between European Americans, African Americans, and East Asians was not an outlier when compared to the distribution for presumed neutral SNPs. We therefore find no evidence for differential or balancing selection in the contemporary pattern of global PER3 allele frequencies.
AB - Period homologue 3 (PER3) is a component of the mammalian circadian system, although its precise role is unknown. A biallelic variable number tandem repeat (VNTR) polymorphism exists in human PER3, consisting of 4 or 5 repeats of a 54-bp sequence in a region encoding a putative phosphorylation domain. This polymorphism has previously been reported to associate with diurnal preference ("morningness" and "eveningness") and delayed sleep-phase syndrome. We have investigated the global allele frequencies of this variant in ethnically distinct indigenous populations. All populations were polymorphic, with the shorter (4-repeat) allele ranging in frequency from 0.19 (Papua New Guinea) to 0.89 (Mongolia). To investigate if allele frequency has been influenced by natural selection, the authors 1) tested for a correlation with latitude and mean annual insolation (incident sunlight energy), using classical markers to correct for historical population differentiation; and they 2) compared allele-frequency difference between European American, African American, and East Asian populations, as measured using FST, to an empirical null distribution of FST values based on a genome-wide dataset of single nucleotide polymorphisms (SNPs) of presumed neutral loci that were previously typed by The SNP Consortium. The variation in allele frequencies between indigenous populations did not show a pattern that would indicate selective pressure on PER3 resulting from day-length variation or mean annual insolation, and the allele-frequency difference between European Americans, African Americans, and East Asians was not an outlier when compared to the distribution for presumed neutral SNPs. We therefore find no evidence for differential or balancing selection in the contemporary pattern of global PER3 allele frequencies.
KW - Circadian rhythms
KW - Day length
KW - Natural selection
KW - PER3
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=27944489110&partnerID=8YFLogxK
U2 - 10.1177/0748730405281332
DO - 10.1177/0748730405281332
M3 - Article
C2 - 16275768
AN - SCOPUS:27944489110
VL - 20
SP - 490
EP - 499
JO - Journal of Biological Rhythms
JF - Journal of Biological Rhythms
SN - 0748-7304
IS - 6
ER -