Intron-exon organization of the active human protein S gene PS alpha and its pseudogene PS beta: duplication and silencing during primate evolution.
The human protein S locus on chromosome 3 consists of two protein S genes, PS alpha and PS beta. Here we report the cloning and characterization of both genes. Fifteen exons of the PS alpha gene were identified that together code for protein S mRNA as derived from the reported protein S cDNAs. Analysis by primer extension of liver protein S mRNA, however, reveals the presence of two mRNA forms that differ in the length of their 5'-noncoding region. Both transcripts contain a 5'-noncoding region longer than found in the protein S cDNAs. The two products may arise from alternative splicing of an additional intron in this region or from the usage of two start sites for transcription. The intron-exon organization of the PS alpha gene fully supports the hypothesis that the protein S gene is the product of an evolutional assembling process in which gene modules coding for structural/functional protein units also found in other coagulation proteins have been put upstream of the ancestral gene of a steroid hormone binding protein. The PS beta gene is identified as a pseudogene. It contains a large variety of detrimental aberrations, viz., the absence of exon I, a splice site mutation, three stop codons, and a frame shift mutation. Overall, the two genes PS alpha and PS beta show between their exonic sequences 96.5% homology. Southern analysis of primate DNA showed that the duplication of the ancestral protein S gene has occurred after the branching of the orangutan from the African apes.(ABSTRACT TRUNCATED AT 250 WORDS)
Ploos van Amstel
H K
HK
Haemostasis and Thrombosis Research Unit, University Hospital, Leiden, The Netherlands.
Reitsma
P H
PH
van der Logt
C P
CP
Bertina
R M
RM
D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D004247:DNA / Q000737:chemistry; D005091:Exons; D015698:Genomic Library; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D005810:Multigene Family; D017293:Protein S; D011544:Pseudogenes; D012333:RNA, Messenger / Q000096:biosynthesis
D006023:Glycoproteins; D017293:Protein S; D012333:RNA, Messenger; D004247:DNA