Sequence variation and phylogenetic history of the mouse Ahr gene.
The Ahr locus encodes for the aryl hydrocarbon receptor (AHR), which plays an important toxicological and developmental role. Sequence variation in this gene was studied in 13 different mouse lines that included eight laboratory strains, two Mus musculus subspecies and three additional Mus species. The data presented represent the largest study of sequence variation across multiple mouse lines in a single gene (approximately equal to 15.9 kb/mouse line). Among all mice, the average frequency of all polymorphisms in the intronic regions was 20.3 variants/kb and the average exonic frequency was 14.1 variants/kb. For substitutions alone, the average frequencies in the intronic and exonic regions for all mice were 13.3 and 8.9 substitutions/kb, respectively. Between laboratory strains, the average intronic and exonic frequencies for all polymorphisms dropped to 5.4 and 2.9 variants/kb, respectively. There were 111 non-synonymous polymorphisms that resulted in 42 different amino acid changes, of which only 10 amino acid changes had been previously identified. Based on the nucleotide sequence, the phylogenetic history of the gene showed mice from the Ahr(b2) and Ahr(d) alleles in separate branches while mice from the Ahr(b1) and Ahr(b3) alleles exhibited a more complex history. Evolutionarily, the AHR protein as a whole appears to be under purifying selective pressure (K(a) : K(s) ratio = 0.237). Despite significant functional constraint in the basic helix-loop-helix and PAS domains, ligand binding is not constrained to the high-affinity allele, which supports further the role of the AHR in development and its importance beyond the adaptive response to environmental toxicants.
Thomas
Russell S
RS
Aeomica, Sunnyvale, California 94085-4520, USA.
Penn
Sharron G
SG
Holden
Kevin
K
Bradfield
Christopher A
CA
Rank
David R
DR
D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D008040:Genetic Linkage; D014644:Genetic Variation; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018336:Receptors, Aryl Hydrocarbon