Evolution of Gene Regulation as Revealed by Differential Regulation of the Chicken Lysozyme Transgene and the Endogenous Mouse Lysozyme Gene in Mouse Macrophages

Abstract

Lysozyme gene expression is a marker for macrophage differentiation in vertebrates. We have previously shown that expression of the complete chicken lysozyme gene domain in macrophages of transgenic mice is directly correlated to the copy number of integrated transgenes. Thus, the chicken lysozyme locus in the mouse acts as an independent regulatory unit irrespective of its random position in the host genome. This finding allowed a comparative analysis of the regulation of the endogenous mouse lysozyme M gene and the chicken lysozyme transgene in the same animal. We demonstrate by transcript analysis of total tissue RNA and by in situ hybridization, that both genes are expressed in macrophages. In macrophages of the same animal the regulation of both genes in response to external signals was distinctly different: the lysozyme transgene responded to various agents influencing macrophage activation, in contrast, mouse lysozyme RNA levels remained unchanged under these conditions. Thus, as in chicken macrophages, the chicken lysozyme expression level in mouse macrophages is coupled to the macrophage activation status, while the mouse lysozyme is not. Our results suggest, that the cis-regulatory elements of lysozyme genes have evolved more rapidly than the function and expression of the trans-acting factors involved in the regulation of macrophage-specific gene activation.