Xanthine dehydrogenase (XDH): Episodic evolution of a "neutral" protein*

We investigated the evolution of xanthine dehydrogenase (Xdh) in 34 species from the three multicellular kingdoms, including one plant, two fungi, and three animal phyla, two classes of vertebrates, four orders of mammals, an d two orders of insects. We adopted a model-based maximum-likelihood framew ork of inference. After accounting for among-site rate variation and hetero geneous nucleotide composition of the sequences using the discrete gan-mia distribution, and using nonhomogeneous nonstationary representations of the substitution process, the rate of amino acid replacement is 30.4 x 10(-10) /site/year when Drosophila species are compared but only approximate to 18 x 10(-10)/site/year when comparisons are made between mammal orders, betwee n insect orders, or between different animal phyla and approximate to 11 x 10(-10)/site/year when comparisons are made between birds and mammals, betw een fungi, or between the three multicellular kingdoms. To account for thes e observations, the rate of amino acid replacement must have been eight or more times higher in some lineages and at some times than in others. Spasti c evolution of Xdh appears to be related to the particularities of the geno mes in which the locus is embedded.