Mutation, Development and Evolution

During my tenure as a graduate student, “Mutation, Development and Evolution” was submitted in May, 1967 as a thesis to the Institute of Animal Genetics, University of Edinburgh. This thesis (Lieber, 1967, DOWNLOAD PDF FILE) anticipated many of the subsequent developments in genetics. At the time, it explored the possibility that cellular processes can convert various chemicals into mutagens, thereby internally increasing the mutation rate in genes, a phenomenon later demonstrated by research and deemed very relevant to the issue of environmental chemicals as a source of mutagenesis and carcinogenesis. The thesis also conjectured that gene boundaries were not absolute but changeable, and this has been shown to be the case through research in molecular genetics. Hypothetical, controlled sequence-changes in M-RNA after transcription was also illustrated, with described implications for gene expression and development, and various examples of this process, such as intron deletion from post-transcriptional M-RNA, have been repeatedly demonstrated through experiment. Furthermore, some enzymes, referred to as genezymes in the thesis, were conjectured as behaving as genes. The discovery of prions would seem to give some evidence of this.

In a concluding section, the thesis proposed a modern version of the pangenesis concept, whereby M-RNA molecules can transmit, via the blood stream, copies of mutant somatic genes into the cells of the germ line, become reversed transcribed into DNA copies, and these DNA copies eventually being incorporated into the genomes of the germ line cells. As pointed out in the thesis, this would enable the eventual transmission of somatic mutations to progeny. (See page 52 of the thesis.) This view was presented three years before Temin and Baltimore demonstrated the reverse transcription of M-RNA into DNA. In 1980, Gorczynski and
Steele proposed a similar process of modern pangenesis to explain how mutant, somatic antigen genes, conferring immune tolerance in mice, had become demonstratedly transmitted to progeny through their experiments.

The thesis presented and illustrated a unifying view that mutagenesis, far from being a random process, can be a highly directed and ordered process within the organism. Being so, it was further postulated that such inner controlled mutation could have provided evolution with a significant inner-parameter, illustrating an inner determination of evolutionary change, as opposed to a strictly selectionist determination of such change.

The thesis was read by C.H. Waddington and Charlotte Auerbach, who was my mentor, and the discoverer of chemically induced mutagenesis. The written corrections and comments in the thesis are hers.

References

Lieber, M. M. (1967). Mutation, Development and Evolution.

DOWNLOAD PDF FILE

Gorczynski, R. and Steele, E. (1980). Inheritance of acquired immunological tolerance to foreign histocompatibility antigens in mice, Proc. Natl. Acad. Sci. USA Vol. 77 No. 5, pp. 2871-2875.

Research described in various genetics textbooks.

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