7. In particular, Zamenhof and his colleagues investigated the alteration of mutability in relation to environmental conditions (Zamenhof et al. 1966), and Leigh considered the adaptive evolution of mutation rate (Leigh 1973). It is also worth mentioning that some of biologists of the Modern Synthesis advanced the hypothesis of directed mutations, not from the point of view of their adaptive value, but as to the place they occur and their abundance (i.e., mutations that would occur in particular genomic sites with a specific probability; Dobzhansky 1951 [1937], 62-63). This hypothesis called into question the wholly random character of all genetic mutations (Mayr 1942, 68). Nevertheless, biologists of the Modern Synthesis were very cautious about this point and always pleaded ignorance of the physiology of the genes and of the chemistry of the mutational process.

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