Experimental adaptation of the bacteriophage phi X174 to a Salmonella host
depressed its ability to grow on the traditional Escherichia host, whereas
adaptation to Escherichia did not appreciably affect growth on Salmonella.
Continued host switching consistently exhibited this pattern. Growth inhibi
tion on Escherichia resulted from two to three substitutions in the major c
apsid gene. When these phages were forced to grow again on Escherichia, fit
ness recovery occurred predominantly by reversions at these same sites, rat
her than by second-site compensatory changes, the more frequently observed
mechanism in most microbial systems. The affected residues lie on the virio
n surface and they alter attachment efficiency, yet they occur iu a region
distinct from a putative binding region previously identified from X-ray cr
ystallography. These residues not only experienced high rates of evolution
in our experiments, but also exhibited high levels of radical amino acid va
riation among phi X174 and its known relatives, consistent with a history o
f adaptation involving these sites.