378 V. THE NATURE OF EVOLUTION 



severe changes raised abruptly appear to be irreversible, while slight 

 changes given rise to gradually may be reversible. 



The recovery of the original structure of protein, as previously 

 considered, is dependent upon the memory of the path along which 

 the change proceeded. If one goes without hurry tramping on the 

 overgrown grass through a pathless field, he will be able to return 

 easily along the beaten path, but if he goes hurriedly in long strides 

 the return will be difficult. In like manner, if proteins are changed 

 in their structure gradually, the return to the original structure will 

 occur with ease, as the structural factor resisting the change may be 

 removed by the gradual change, whereas in an extensive change raised 

 abruptly the recovery of the original structure may be unable. This 

 latter change must be mutation, while the former the reversible 

 alteration of the gene. 



It will be expected from this concept that in mutation the re- 

 covery of the original structure may be never impossible but only 

 difficult. In fact, it has gradually become acknowledged that reversible 

 mutation, commonly called back mutation, is by no means a rare occur- 

 rence. As pointed out previously, even so great a change as that of 

 somatic cell into cancer is reversible if the most favourable condition 

 for the reversion is applied. It has been claimed that exposure to 

 X-ray and ultraviolet-light irradiation increases the back mutation 

 rate of microorganisms very substantially (63), indicating that appro- 

 priate stimuli can also necessary for the promotion of the back 

 mutation. 



The frequency of back mutation of bacteria from streptomycin- 

 dependence to non-dependence is greatly increased by the treatment 

 with ferrous compounds. According to Catlin (64) streptomycin-depen- 

 dent colon bacilli show a considerably higher frequency of reversion 

 to streptomycin-nondependence after exposure to ferrrous compounds 

 at 1°C. than after comparable treatment at 37°C. This suggests that 

 in this case ferrous compounds may only contribute to initiate the 

 return to the original structure which may be stable at lower tem- 

 peratures. It should be remembered in this connection that besides 

 ferrous compounds, ultraviolet and X-rays, and a number of chemicals 

 such as manganeous compounds, also effective in the promotion of this 

 back mutation. 



According to our observation, phage is frequently changed in its 

 property by unknown causes to produce small plaque, which indicates 

 the reduction of its virulence, and the changed property is sometimes 

 inherited, showing that the change is a mutation. The maintenance 

 of the changed property appears to be connected with the medium in 

 which the phage affected the host bacteria. For example, as shown 



