Repeated hybridization and selection among wild-type isolates produced strains of with increased penicillin titre. Four independent selection lines were established, each originating from a sexual cross between two different heterokaryon-incompatible wild-type isolates. In each generation, two selected high-titre sister strains were crossed to produce the next generation. An initial increase in titre was obtained in each line, but after four or five generations of selection the genetic variation was considerably reduced and the rate of response to selection had decreased. From a base population of wild-type isolates with a mean titre of 8.6 units/ml the progeny mean titre was raised to between 16 and 20 units/ml in each line. The gradual nature of the response suggests that a number of genes determine penicillin titre in the wild-type isolates used. The gene action throughout the selection programme was predominantly additive.


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