Evolution of Rodent Lysozymes: Isolation and Sequence of the Rat Lysozyme Genes

Abstract

Mice have two lysozyme c genes that are the products of a gene duplication. The rat genome also possesses two lysozyme genes, which implies that the duplication of the lysozyme gene preceded the mouse-rat divergence. Concerted evolution has homogenized the 3′ half (middle of exon 2 through 3′ flanking) of the genes in each species. A mosaic pattern of concerted evolution is found for the 5′ half of the gene, with both the 5′ and 3′ ends, but not the middle, of exon 1 evolving in a concerted fashion. Differences exist in the homogenization pattern in the rat and mouse, suggesting the existence of species-specific patterns of concerted evolution. Exon 1 contains most of the amino acid substitutions that distinguish mouse M from mouse P lysozyme or rat 1 from rat 2 lysozyme. Some of the amino acid differences found between mouse lysozyme genes are found also in the rat, and they suggest that rat 1 and 2 are homologous to mouse M and P, respectively. Nuclease S1 mapping indicated that only the rat 1 gene is expressed at detectable levels, and, specifically, that this gene is expressed by cells in the lung, small intestine, and spleen. The mouse expresses different lysozyme genes in the intestinal (P) and macrophage (M) cells, while the rat expresses only one gene in both of these tissues. The absence of detectable expression and the accumulation of a large number of amino acid substitutions in the parts of exons 1 and 2 of the rat 2 gene not participating in concerted evolution suggest that the rat 2 gene is a pseudogene.