Expression reduction in mammalian strongXstrong chromosome evolution.pdf

Expression reduction in mammalian X chromosome evolution refutes Ohno’s hypothesis of dosage compensation a a b,1 a,1 Fangqin Lin , Ke Xing , Jianzhi Zhang , and Xionglei He aKey Laboratory of Gene Engineering of Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China; and bDepartment of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109 Edited by Masatoshi Nei, Pennsylvania State University, University Park, PA, and approved June 08, 2012 (received for review January 31, 2012) Susumu Ohno proposed in 1967 that, during the origin of number of authors subsequently noted that the fraction of inactive mammalian sex chromosomes from a pair of autosomes, per-allele genes is greater in X than in autosomes and that X:AA ∼1 when expression levels of X-linked genes were doubled to compensate only active genes are considered (14–17). We suggested that the for the degeneration of their Y homologs. This conjecture forms extra inactive genes in X originated from the most weakly the foundation of the current evolutionary model of sex chromo- expressed genes in X as a consequence of Y degeneration, and some dosage compensation, but has been tested in mammals only that X:AA ∼0.5 when appropriate sets of active genes are com- indirectly via a comparison of expression levels between X-linked pared (13). Nevertheless, all of the above are indirect tests of and autosomal genes in the same genome. The test results have Ohno’s hypothesis and are thus inconclusive (13, 18). Fortunately, been controversial, because examinations of different gene sets this problem can be circumvent