Evolutionary analysis links <i>Ahr</i> to movement.

<p>(<b>A</b>) Phylogenetic BLAST analysis of mouse <i>Ahr</i> showed that the gene is highly conserved down to simple multicellular animals such as <i>C. elegans</i>, the gene likely has conserved basic metabolic functions. (<b>B</b>) Sequence analysis of the three missense mutations of <i>Ahr</i> between B6 and D2 known to have an impact oh AHR activity (375, 471, 805). (<b>C</b>) B6 mice with the humanized AHR allele are nearly twice as active as controls. The humanized AHR allele is similar to the D2 allele in many tests of enzymatic activity, with a ∼90%+ reduction in activity compared to the B6 allele <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004673#pgen.1004673-Connor1" target="_blank">[24]</a>. (<b>D</b>) <i>D. melanogaster</i> with a heterozygous deletion allele of the <i>Ahr</i> ortholog <i>ss</i> are also significantly more active than controls. The 50% reduced expression appears to increase movement by about 20% in both males and females. Each comparison is a separate Welch's <i>t</i>-test with <i>p</i><0.001. Females are ∼30% less active than males in both instances (<i>p</i><0.001). (<b>E</b>) <i>C. elegans</i> treated from early development with RNAi for <i>ahr-1</i> are nearly twice as active as worms treated with a control vector. Reduced doses of RNAi have intermediary effects on activity. <i>p</i> = 2.9e-6 for 100% vs. empty vector (ev).