Molecular evolution of an ancient mariner transposon, Hsmar1, in the human genome.

A confident consensus sequence for Hsmar1, the first mariner transposon recognized in the human genome, was generated using three genomic and 15 cDNA sequences. It is thought to represent the ancestrally active copy that invaded an early primate genome. The consensus is 1287 base pairs (bp) long, has 30 bp perfect inverted terminal repeats (ITRs), and encodes a 343 amino acid (aa) mariner transposase. Each copy has diverged from the consensus largely independently of the others and mostly neutrally, and most are now defective. They differ from the consensus by an average of 7.8% in DNA sequence and 7.5 indels per kilobase, both of which values indicate that the copies were formed about 50 Myr ago. On average, only 20% of the 73 surmised CpG hypermutable sites in the consensus remain. A remarkable exception to this loss of functionality is revealed by a set of ten cDNA clones derived from a particular genomic copy that has diverged only 2.4% from the consensus, retained 54% of its hypermutable CpG pairs, and which has a full-length transposase open reading frame. The complete sequence of one of these cDNAs (NIB1543) indicates that the transposase gene of this copy may have been conserved because it is spliced to a human cellular gene encoding a SET domain protein. A specific PCR assay was used to reveal the presence of Hsmar1 copies in all primates examined representing all major lineages, but not in close relatives of primates. PCR fragments cloned and sequenced from a representative sample of primates confirmed that Hsmar1 copies are present in all major lineages, and also revealed another cecropia subfamily mariner in prosimians only, and a third highly divergent mariner present in the greater slow loris Nycticebus coucang. There are about 200 copies of Hsmar1 in the human genome, as well as +/-2400 copies of a derived 80 bp paired ITR structure and +/-4600 copies of solo ITRs. Thus, this transposon had a considerable insertional mutagenic effect on past primate genomes.