BackgroundChlamydia (C.) psittaci, the causative agent of avian chlamydiosis and human psittacosis, is a genetically heterogeneous species. Its broad host range includes parrots and many other birds, but occasionally also humans (via zoonotic transmission), ruminants, horses, swine and rodents. To assess whether there are genetic markers associated with host tropism we comparatively analyzed whole-genome sequences of 61C. psittacistrains, 47 of which carrying a 7.6-kbp plasmid.ResultsFollowing clean-up, reassembly and polishing of poorly assembled genomes from public databases, phylogenetic analyses usingC. psittaciwhole-genome sequence alignment revealed four major clades within this species. Clade 1 represents the most recent lineage comprising 40/61 strains and contains 9/10 of the psittacine strains, including type strain 6BC, and 10/13 of human isolates. Strains from different non-psittacine hosts clustered in Clades 2– 4. We found that clade membership correlates with typing schemes based on SNP types,ompAgenotypes, multilocus sequence types as well as plasticity zone (PZ) structure and host preference. Genome analysis also revealed that i) sequence variation in the major outer membrane porin MOMP can result in 3D structural changes of immunogenic domains, ii) past host change of Clade 3 and 4 strains could be associated with loss of MAC/perforin in the PZ, rather than the large cytotoxin, iii) the distinct phylogeny of atypical strains (Clades 3 and 4) is also reflected in their repertoire of inclusion proteins (Inc family) and polymorphic membrane proteins (Pmps).ConclusionsOur study identified a number of genomic features that can be correlated with the phylogeny and host preference ofC. psittacistrains. Our data show that intra-species genomic divergence is associated with past host change and includes deletions in the plasticity zone, structural variations in immunogenic domains and distinct repertoires of virulence factors.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12864-023-09370-w.