PRIMARY SEQUENCE OF BABOON CR-1 DEMONSTRATES CONCERTED EVOLUTION WITHIN THE CR-1 GENE

Complement receptor type one (CRI) in primates has several remarkable structural features including a size polymorphism (M-r 190 000, 220 00 0, 250 000 and 280 000) in man, multiple size variants (M-r 55 000-220 000) among non-human primates, and a partial amino-terminal duplicati on (CR1-like gene) that appears to encode the short (55 000-70 000) fo rms expressed on primate erythrocytes. In general, these short CR1 for ms, some of which are GPI anchored, are expressed on erythrocytes and the 220 000 molecular weight CR1 form is expressed on PBMC, except in man, where only the 220 000 molecular weight form has been detected. I n addition, the M-r 220 000 human CRI sequence carries several long in ternal repeats of up to 99% homology. It has been suggested that the h ighest homology is maintained by gene conversion and/or unequal crosso ver. To address further the evolutionary and biologic implications of these multiple forms, a 6 kb cDNA encoding baboon CR1(220) was identif ied by RTPCR using human CR1 primers. Its sequence contains the expect ed 30 complement control protein repeats (CCP) and demonstrates an ove rall homology to human CRI of 95.4% at the nucleotide level and 93.2% at the amino acid level. As in human CR1, the first 28 CCP maintain th e characteristic ''seven CCP-long homologous repeats (LHR)'' organizat ion. Analysis of baboon CR1(220) indicates that horizontal or concerte d evolution has maintained a high degree (> 98%) of identity between c orresponding CCP within the LHRs from CCP 4 to CCP 19, while this homo logy region extends from CCP 3 to CCP 18 in man. In contrast, substitu tions occurring in other CCP are not propagated to the corresponding s ites of other LHR. Sequence differences in CCP 1, 2 and 3 are likely t o be related to the acquisition of enhanced C3b binding capability by this amino-terminal region of the protein. Thus, the sequence data str ongly support the hypotheses that gene conversion and or unequal cross over events have driven the evolution of the protein in regions of hig h homology while selective forces, probably ligand binding requirement s, have maintained the regions of divergence. (C) 1997 Elsevier Scienc e Ltd.