Systematically reported as Mycobacterium caprae: phylogenomic characterisation and diagnostic markers of La4, a rare animal-adapted lineage of the M. tuberculosis complex

The Mycobacterium tuberculosis complex (MTBC) includes animal-adapted lineages whose diversity remains underestimated, and a lineage absent from nomenclature is invisible to surveillance. We present the first phylogenomic characterisation of La4, proposed as sister to M. caprae but absent from the most recent MTBC reference review. Assembling all 25 publicly available La4 sequencing runs (20 unique isolates) from seven countries and six host categories, we resolve two sister clades, a basal wild-mammal clade (5 strains) and a derived primate clade (20 strains), delimited by exclusive derived markers rather than by branch support alone. La4 is strictly reciprocally monophyletic with M. caprae: none of 278 available M. caprae genomes carries any of 158 La4 core-exclusive markers. Ancestral state reconstruction supports an ungulate origin at order level. Despite this distinctness, all four typing systems assign La4 to M. caprae or M. bovis, and primary literature has already published La4 genomes as M. caprae on three independent occasions across eight years, three continents and unrelated groups. We define 158 core-exclusive markers that discriminate La4 independently of any classification framework, and document two zoonotic human cases. Genome-wide divergence is neutral (McDonald-Kreitman DoS = -0.04, p = 0.50). At the ESX-2 secretion locus, an esxC frameshift inherited from the animal-clade ancestor is distinguished from a whole-locus deletion specific to the wild clade, settling a question left open by earlier work. La4 is thus an independent, diagnosable MTBC lineage of ungulate origin whose principal epidemiological feature is that it is routinely reported as something else.