Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis 
recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; 
however, it is not known at what point Y. pestis gained the ability to induce a 
fulminant pneumonia. Here we show that the acquisition of a single gene encoding 
the protease Pla was sufficient for the most ancestral, deeply rooted strains of 
Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to 
infect the lungs at a very early stage in its evolution. As Y. pestis further 
evolved, modern strains acquired a single amino-acid modification within Pla 
that optimizes protease activity. While this modification is unnecessary to 
cause pneumonic plague, the substitution is instead needed to efficiently induce 
the invasive infection associated with bubonic plague. These findings indicate 
that Y. pestis was capable of causing pneumonic plague before it evolved to 
optimally cause invasive infections in mammals.