Sequence diversity and molecular evolution of the leukotoxin (lktA) gene in bovine and ovine strains of Mannheimia (Pasteurella) haemolytica

The molecular evolution of the leukotoxin structural gene (lktA) of Mannhei mia (Pasteurella) haemolytica was investigated by nucleotide sequence compa rison of lktA in 31 bovine and ovine strains representing the various evolu tionary lineages and serotypes of the species. Eight major allelic variants (1.4 to 15.7% nucleotide divergence) were identified; these have mosaic st ructures of varying degrees of complexity reflecting a history of horizonta l gene transfer and extensive intragenic recombination. The presence of ide ntical alleles in strains of different genetic backgrounds suggests that as sortative (entire gene) recombination has also contributed to strain divers ification in M. haemolytica. Five allelic variants occur only in ovine stra ins and consist of recombinant segments derived from as many as four differ ent sources. Four of these alleles consist of DNA (52.8 to 96.7%) derived f rom the lktA gene of the two related species Mannheimia glucosida and Paste urella trehalosi, and four contain recombinant segments derived from an all ele that is associated exclusively with bovine or bovine-like serotype A2 s trains. The two major lineages of ovine serotype A2 strains possess lktA al leles that have very different evolutionary histories and encode divergent leukotoxins (5.3% amino acid divergence), but both contain segments derived from the bovine allele. Homologous segments of donor and recipient alleles are identical or nearly identical, indicating that the recombination event s are relatively recent and probably postdate the domestication of cattle a nd sheep. Our findings suggest that host switching of bovine strains from c attle to sheep, together with inter- and intraspecies recombinational excha nges, has played an important role in generating leukotoxin diversity in ov ine strains. In contrast, there is limited allelic diversity of lktA in bov ine strains, suggesting that transmission of strains from sheep to cattle h as been less important in leukotoxin evolution.