Immunogenetics (2004) 56: 631–638 DOI 10.1007/s00251-004-0731-9 ORIGINAL PAPER C A McLure . J F Williamson . B J Stewart . P J Keating . R L Dawkins Genomic analysis reveals a duplication of eight rather than seven short consensus repeats in primate CR1 and CR1L: evidence for an additional set shared between CR1 and CR2 Received: 9 September 2004 / Revised: 4 October 2004 / Published online: 30 October 2004 # Springer-Verlag 2004 Abstract We report the discovery of previously unrecog- nised short consensus repeats (SCRs) within human and chimpanzee CR1 and CR1L. Analysis of available ge- nomic, protein and expression databases suggests that these are actually genomic remnants of SCRs previously reported in other complement control proteins (CCPs). Comparison with the nucleotide motifs of the 11 defined subfamilies of SCRs justifies the designation g-like because of the close similarity to the g subfamily found in CR2 and MCP . To date, we have identified five such SCRs in human and chimpanzee CR1, one in human and chimpanzee CR1L, but none in either rat or mouse Crry in keeping with the number of internal duplications of the long homologous repeat (LHR) found in CR1 and CR1L. In fact, at the genomic level, the ancestral LHR must have contained eight SCRs rather than seven as previously thought. Since g-like SCRs are found immediately downstream of d SCRs, we suggest that there must have been a functional dg set which has been retained by CR2 and MCP but which is degenerate in CR1 or CR1L. Interestingly, dg is also present in the CR2 component of mouse CR1. The degeneration of the g SCR must have occurred prior to the formation of primate CR1L and prior to the duplication events which resulted in primate CR1. In this context, the apparent conservation of g-like SCRs may be surprising and may suggest the existence of mechanisms unrelated to protein coding. These results provide examples of the many processes which have contributed to the evolution of the extensive repertoire of CCPs. Keywords Complement control proteins . Short consensus repeats . CR1 . CR1-L . Evolution . Duplication . Degeneracy Introduction Short consensus repeats (SCRs) or Sushi elements are protein domains of approximately 60 amino acids, including the C . . . C . . . C . . . W. . . C motif (Reid et al. 1986; Hourcade et al. 1989; Krushkal et al. 2000). Diverse versions occur in many vertebrate proteins and have also been found in invertebrates and even viruses. A remarkable feature of SCRs is their repetitive nature, implying that contiguous copies, and therefore combina- tions, are important to the function of the intact native protein. It may not be surprising that SCRs have been implicated in many protein–protein interactions such as those underlying innate immunity, self–non-self recogni- tion, foetomaternal tolerance and cascades such as those involved in coagulation and complement mediated in- flammation. Included within these proteins are comple- ment components (such as Bf and C2) and complement control proteins [(CCPs) such as complement receptors]. With the aim of understanding the evolution of these functions, we have analysed a database of vertebrate SCRs and have asked how each relates to others. We confirm that almost all belong to only 11 subfamilies, tentatively designated a, b, c, d, e, f, g, h, i, j or k (McLure et al. 2004). Different proteins contain specific combinations of representatives of the subfamilies and particular sets such Manuscript number 0406 of the Centre for Molecular Immunology and Instrumentation of the University of Western Australia C. A. McLure . J. F. Williamson . B. J. Stewart . R. L. Dawkins Centre for Molecular Immunology and Instrumentation, University of Western Australia, Canning Vale South, P.O. Box 5100 Nedlands, Western Australia, 6907, Australia C. A. McLure . J. F. Williamson . B. J. Stewart . P. J. Keating . R. L. Dawkins C.Y. O’Connor ERADE Village, P.O. Box 5100 Canning Vale, Western Australia, 6155, Australia R. L. Dawkins (*) Centre for Molecular Immunology and Instrumentation, University of Western Australia, P.O. Box 5100 Canning Vale South, Western Australia, 6155, Australia e-mail: cmii@cyllene.uwa.edu.au Fax: +61-8-93971559