The leukotoxin protein of Mannheimia haemolytica belongs to the HlyA-like subfamily of cytotoxic RTX (repeats in toxin) proteins. To test the hypothesis that different lineages of genus Mannheimia gained the leukotoxin operon via horizontal gene transfer we used a strategy that combines compositional and phylogenetic methods: (i) ranking of genes according to their convergence to the average genome signature of M. haemolytica based on the relative 3:1 dinucleotide bias in 56 individual genes; (ii) estimation of ancestral character states on a phylogeny of 43 Mannheimia strains based on 16S rRNA sequences; (iii) phylogeny of 24 leukotoxin gene sequences and 16 homologous genes retrieved from SWISS-PROT by using PSI-BLAST. Our data show no evidence for horizontal gene transfer into this clade. We propose that vertical descent from the common ancestor of genus Mannheimia, with subsequent loss of these genes in many strains can explain the patchy distribution of leukotoxin in this clade. Finally, we argue that antagonistic pleiotropy was the main contributor to gene loss in the radiating M. ruminalis lines, which have adapted to different ecological niches in the rumen offering different conditions of growth.