Concerted evolution of exons and introns in the MHC-linked tenascin-X gene of mammals.

Two modes of evolution of repeated domains in proteins have been described: (1) a conservative mode, whereby individual domains are conserved across gene duplication and speciation events, and (2) a concerted mode, whereby repeat domains become homogenized within a gene, presumably by intragenic partial duplication and/or gene conversion. The evolution of repeated EGF-like and fibronection-type-III-like (Fn-III) domains in the vertebrate extracellular matrix proteins tenascin-X (TNX) and tenascin-C (TNC) was studied by comparisons between human and mouse orthologs and between the paralogous TNC and TNX genes. The EGF-like repeats have largely been homogenized within each gene by concerted evolution since the duplication of the two genes but have been conserved since the divergence of rodents and primates. The Fn-III domains of TNC have likewise mainly evolved in a conservative fashion since the divergence of rodents and primates. In contrast, the Fn-III repeats of TNX fall into three distinct categories with regard to mode of evolution: (1) The three C-terminal repeats have been conserved since before duplication of the TNX and TNC genes. (2) Certain other repeats have been homogenized within each gene since gene duplication but have been conserved since the divergence of rodents and primates. (3) Still other repeats have evolved in a concerted fashion in rodent and primate lineages since their divergence. Remarkably, certain introns adjacent to the exons encoding these concertedly evolving Fn-III repeats have themselves evolved in a concerted fashion. This is the first known example of concerted evolution of repeated introns within a protein-coding gene.