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Conservation Throughout Mammalia and Extensive Protein-Encoding Capacity of the Highly Repeated DNA Long Interspersed Sequence One

Frank H. Burton, Daniel D. Loeb, Charles F. Voliva, Sandra L. Martin, Marshall H. Edgell and Clyde A. Hutchison, III

Department of Microbiology and Immunology, Curriculum in Genetics, Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27514, U.S.A.

We report an investigation of the structure, evolutionary history, and function of the highly repeated DNA family named Long Interspersed Sequence One (Ll). Hybridization studies show, first, that Ll is present throughout marsupial and placental mammalian orders. Second, Ll is more homologous within these species than between them, which suggests that it has undergone concerted evolution within each mammalian lineage. Third, on the whole Ll diverges in accordance with the fossil record. This suggests that it arose in each lineage rather by inheritance from a common ancestral family, which was present in the progenitor to mammals, than by cross-species transmission. Alignment of 1.6 x 103 bases of primate and mouse Ll DNA sequences shows a predominance of silent mutations within aligned long open reading frames, indicating that at least this part of Ll has produced functional protein. The observation of additional long open reading frames in further unaligned DNA sequences suggests that a minimum of 3.2 x 103 bases or at least half of the Ll structure is a protein-coding sequence. Thus Ll, which contains about 100,000 members in mouse, is by far the most repetitive family of which a subset comprises functional protein-encoding genes. The ability of the putative protein-encoding regions of mouse Ll to hybridize to Ll homologs throughout the Mammalia implies that these sequences have been subject to conservative selection upon protein function in all mammalian lineages, rather than in a few. Ll is therefore a highly repeated family of genes with both a widespread and an ancient history of function in mammals.

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