Who Ate Whom? Adaptive Helicobacter Genomic Changes That Accompanied a Host Jump from Early Humans to Large Felines

Abstract

Helicobacter pylori infection of humans is so old that its population genetic structure reflects that of ancient human migrations. A closely related species, Helicobacter acinonychis, is specific for large felines, including cheetahs, lions, and tigers , whereas hosts more closely related to humans harbor more distantly related Helicobacter species. This observation suggests a jump between host species. But who ate whom and when did it happen? In order to resolve this question, we determined the genomic sequence of H. acinonychis strain Sheeba and compared it to genomes from H. pylori. The conserved core genes between the genomes are so similar that the host jump probably occurred within the last 200,000 (range 50,000–400,000) years. However, the Sheeba genome also possesses unique features that indicate the direction of the host jump, namely from early humans to cats. Sheeba possesses an unusually large number of highly fragmented genes, many encoding outer membrane proteins, which may have been destroyed in order to bypass deleterious responses from the feline host immune system. In addition, the few Sheeba-specific genes that were found include a cluster of genes encoding sialylation of the bacterial cell surface carbohydrates, which were imported by horizontal genetic exchange and might also help to evade host immune defenses. These results provide a genomic basis for elucidating molecular events that allow bacteria to adapt to novel animal hosts.

Synopsis

Little is known about the mechanisms that allow jumps of parasites from one host species to a second. We describe the genomic sequence of strain Sheeba of Helicobacter acinonychis, a bacterial parasite that can cause severe gastritis of tigers, lions, and cheetahs. The genomic sequence possesses an unusually high number of defective genes that have been fragmented through frameshift mutations, stop codons, and small insertions and deletions. Together with phylogenetic analyses, these observations indicate that H. acinonychis arose 200,000 years ago via a host jump of Helicobacter pylori from early humans. H. acinonychis also possesses five genes involved in sialylation of cell surface carbohydrates that were probably acquired by horizontal gene transfer from unrelated bacteria. Epitopes on the bacterial cell surface were diminished by gene fragmentation (inactivation of outer membrane proteins) and sialylation (masking of carbohydrates), which should facilitate the evasion of feline immune defenses, and may have been crucial for the host jump.