Analysis of human CYP1A1 and CYP1A2 genes and their shared bidirectional promoter in eight world populations.
The human CYP1A1_CYP1A2 locus comprises the CYP1A1 (5,988 bp) and CYP1A2 (7,759 bp) transcribed regions, oriented head-to-head, sharing a bidirectional promoter of 23,306 bp. The older CYP1A1 gene appears more conserved and responsible for critical life function(s), whereas the younger CYP1A2 gene might have evolved more rapidly due to environmental (dietary) pressures. A population genetics study might confirm this premise. We combined 60 CYP1A1_CYP1A2 SNPs found in the present study (eight New Guinea Highlanders, eight Samoans, four Dogrib, four Teribe, four Pehuenche, and one Caucasian) with those found in a previous study (six West Africans, four Han Chinese, six Germans, four Samoans, and four Dogrib), yielding a total of 106 SNPs in 106 chromosomes. Resequencing of Oceanians plus Amerindians in the present study yielded 21 New World SNPs ( approximately 20%), of which 17 are not previously reported in any SNP database. Various tests revealed selective pressures for both genes and both haploblocks; unfortunately, differences in rates of evolution between the two genes were undetectable. Fay & Wu's H test revealed a "hitchhiking event" centered around four SNPs in the CYP1A1 3'-UTR; a study in silico identified different microRNA-binding patterns in the hitchhiked region, when the mutations were present compared with the mutations absent.
Department of Environmental Health, University of Cincinnati Medical Center, PO Box 670056, Cincinnati, OH 45267-0056, USA. dan.nebert@uc.edu
Lucia F
LF
Jorge-Nebert
Zhengwen
Z
Jiang
Ranajit
R
Chakraborty
Joanna
J
Watson
Li
L
Jin
Stephen T
ST
McGarvey
Ranjan
R
Deka
Daniel W
DW
Nebert
D044467:American Indian or Alaska Native / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic; D005828:Genetics, Population; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044469:Racial Groups / Q000145:classification / Q000235:genetics*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
D035683:MicroRNAs; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2