The end of gonad-centric sex determination in mammals - PubMed
The end of gonad-centric sex determination in mammals
Arthur P Arnold. Trends Genet. 2012 Feb.
Abstract
The 20th-century theory of mammalian sex determination states that the embryo is sexually indifferent until the differentiation of gonads, after which sex differences in phenotype are caused by the differential effects of gonadal hormones. However, this theory is inadequate because some sex differences precede differentiation of the gonads and/or are determined by non-gonadal effects of the sexual inequality in the number and type of sex chromosomes. In this article, I propose a general theory of sex determination, which recognizes multiple parallel primary sex-determining pathways initiated by genes or factors encoded by the sex chromosomes. The separate sex-specific pathways interact to synergize with or antagonize each other, enhancing or reducing sex differences in phenotype.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Figures

Four possible classes of primary sex determining factors are recognized. Class I comprises Y genes that have a male-specific effect in one or more tissues, such as Sry and Y genes required for spermatogenesis. Class II are X genes that are expressed at a higher level in females than males by virtue of the 2:1 ratio in number of X chromosomes. Class III are X genes that receive a parental imprint. The X chromosome receiving a maternal imprint (Xm, yellow) is active in half of XX cells and all of XY cells, whereas the X chromosome receiving a paternal imprint (Xp, blue) is active in half of XX cells and no XY cells. Class IV are proposed regions of sex chromosome heterochromatin (the heterochromatic inactive X (Xi) is illustrated here) that act as sex-specific sinks for factors (red dots) that regulate the amount of euchromatin / heterochromatin at interphase and therefore affect gene expression throughout the genome. To date, specific members of only Class I have been identified (Sry and spermatogenesis genes [9,10,11]). Although evidence indicates that the number of X chromosomes leads to some sex differences in phenotype [50], the specific genes or chromosome regions that explain these X effects have not been identified. Class IV is particularly speculative at present because it is based on a limited number of studies. Future studies are likely to expand the importance of Classes II–IV.
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