GENOMIC STRUCTURE AND EVOLUTION OF A NOVEL GENE (PLA2L) WITH DUPLICATED PHOSPHOLIPASE A(2)-LIKE DOMAINS

In a previous study, we isolated a novel human cDNA with two domains o f homology to secreted phospholipase A(2) (sPLA(2)) embedded within a much larger open reading frame. The corresponding gene, termed PLA2L, is also unusual in that it is transcribed from an endogenous retrovira l long terminal repeat promoter in teratocarcinoma cell lines. The ass ociated retroviral element, a member of the HERV-H family of sequences , is found within an intron of the human PLA2L gene and has apparently assumed transcriptional regulatory functions at this locus. In this s tudy, we have isolated genomic clones spanning the human PLA2L locus a nd have determined the intron/exon structure of the PLA(2)-like domain s. This intron/exon structure is very similar to that of known sPLA(2) s despite the fact that the PLA2L gene is highly diverged and has a no vel duplicated structure. We also mapped PLA2L to chromosome 8q24, a l ocation that differs from the known locations of human sPLA(2)s. Genom ic PCR across primate species was performed to determine the approxima te time of integration of the HERV-H element. Results indicate that th e element integrated 15-20 million years ago since it is present in ch impanzee and gorilla but absent in orangutan and lower primates. Altho ugh the function of the PLA2L gene is not known, genomic Southern anal yses suggest evolutionary conservation in mammals. These results contr ibute to our understanding of the unique and complex evolutionary hist ory of the PLA2L gene. (C) 1997 Academic Press