Primary sequence of baboon CR1 demonstrates concerted evolution within the CR1 gene.
Complement receptor type one (CR1) in primates has several remarkable structural features including a size polymorphism (Mr 190000, 220000, 250000 and 280000) in man, multiple size variants (Mr 55000-220000) among non-human primates, and a partial amino-terminal duplication (CR1-like gene) that appears to encode the short (55000-70000) forms expressed on primate erythrocytes. In general, these short CR1 forms, some of which are GPI anchored, are expressed on erythrocytes and the 220000 molecular weight CR1 form is expressed on PBMC, except in man, where only the 220000 molecular weight form has been detected. In addition, the Mr 220000 human CR1 sequence carries several long internal repeats of up to 99% homology. It has been suggested that the highest homology is maintained by gene conversion and/or unequal crossover. To address further the evolutionary and biologic implications of these multiple forms, a 6 kb cDNA encoding baboon CR1(220) was identified by RTPCR using human CR1 primers. Its sequence contains the expected 30 complement control protein repeats (CCP) and demonstrates an overall homology to human CR1 of 95.4% at the nucleotide level and 93.2% at the amino acid level. As in human CR1, the first 28 CCP maintain the characteristic "seven CCP-long homologous repeats (LHR)" organization. Analysis of baboon CR1(220) indicates that horizontal or concerted evolution has maintained a high degree (> 98%) of identity between corresponding CCP within the LHRs from CCP 4 to CCP 19, while this homology region extends from CCP 3 to CCP 18 in man. In contrast, substitutions occurring in other CCP are not propagated to the corresponding sites of other LHR. Sequence differences in CCP 1, 2 and 3 are likely to be related to the acquisition of enhanced C3b binding capability by this amino-terminal region of the protein. Thus, the sequence data strongly support the hypotheses that gene conversion and or unequal crossover events have driven the evolution of the protein in regions of high homology while selective forces, probably ligand binding requirements, have maintained the regions of divergence.
Clemenza
L
L
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
Subramanian
B
B
Hourcade
D
D
Nickells
M
M
Atkinson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D019143:Evolution, Molecular; D004854:Herpesvirus 4, Human; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D010215:Papio; D011485:Protein Binding / Q000276:immunology; D017463:Receptors, Complement 3b / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D008024:Ligands; D017463:Receptors, Complement 3b