MOLECULAR EVOLUTION OF THE 2ND ANCIENT HUMAN MARINER TRANSPOSON, HSMAR2, ILLUSTRATES PATTERNS OF NEUTRAL EVOLUTION IN THE HUMAN GENOME LINEAGE

A consensus sequence for the second ancient mariner identified in the human genome, Hsmar2, was constructed by majority rule from full-lengt h and partial sequences of 44 of the +/-1000 copies in the genome. Thi s 1300 base pair (bp) consensus has 31 bp imperfect terminal repeats ( ITRs) and encodes a 351 amino acid (aa) mariner transposase. The seque nce of this transposase has allowed classification of Hsmar2 as a basa l lineage of the irritans subfamily of mariners, sharing at most 38% a a identity with other members of the subfamily. The individual copies in the human genome are all highly mutated from the consensus, having suffered numerous small and some large insertions and deletions (indel s), including many insertions of S and J subfamily Alu elements. The c opies differ, on average, from the consensus by 11.6%, have suffered 1 1.8 indels per kilobase (kb), and only 3.7% of the 30 hypermutable CpG dinucleotide pairs in the consensus remain intact. This level of dive rgence indicates that the ancestrally active Hsmar2 element represente d by the consensus was present in the human genome lineage about 80 mi llion years (Myr) ago. Each copy has apparently evolved since then lar gely independently of the others, and with little constraint on its tr ansposase coding capacity. This pattern of molecular evolution fits th e current model for mariner transposon evolution. These copies provide multiple independent datasets for evaluating the pattern of neutral e volution in the human genome, for example, they confirm that most inde ls are very short and that deletions are twice as common as insertions . (C) 1997 Elsevier Science B.V.