Gender Differences Found in Genes Expressed by Liver

Their finding is to appear in the November 1, 2003, issue of Genes & Development.

Male and female livers express different subsets of genes, which affect the liver's ability to metabolize certain drugs and hormones. This affects numerous processes, such as reproduction. Although this difference has been known for decades, only recently have researchers begun to uncover the genes involved. Now they have discovered the two neighboring genes, Rsl1 and Rsl2, that repress male-specific gene expression. They found that female mice harboring mutations in Rsl genes aberrantly turn on male-specific liver genes, causing the female livers to adopt characteristically male patterns of gene expression.

The Rsl genes appear to function through a division of labor, with each regulating a subset of male-specific genes. While these appear to share the control of normal hepatic gene expression, under some circumstances one may be able to compensate for defects in the other. The researchers determined that the two genes belong to a large family of structurally related genes called the KRAB-SFP gene family, with more than 200 members in the mouse and human genomes.

These genes may be most interesting from an evolutionary perspective, suggests Dr. Diane Robins, part of the research team at the University of Michigan Medical School (Ann Arbor, USA). "This gene family has arisen recently in evolution and diversified rapidly, but the way it acts is highly conserved. Since Rsl regulates genes at puberty that are involved in reproduction and hormone metabolism, it may be that not only Rsl but also other members of the KRAB-ZFP family influence functions that lead to speciation.”




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University of Michigan Medical School