Academic journal article Genetics

Hermann Muller on Measuring Mutation Rates

Academic journal article Genetics

Hermann Muller on Measuring Mutation Rates

Article excerpt

The task of actually counting mutations [...] to compare their frequencies of occurrence [...] would have seemed almost like that of counting needles in haystacks, to compare their frequencies, or like making graphs to show the rates of occurrence of gold pieces on streets of different types. H. J. Muller (1928)

For the pioneers of genetics, mutants were precious. Although they were extremely useful, mutants with readily detectable phenotypes were so rare that it was as impractical to measure mutation rates as to measure the average number of needles in a haystack.

But Hermann Joseph Muller (with contributions from Edgar Altenburg) developed a reliable approach for assaying mutation rate. Muller's methods, published in GENETICS in 1928, helped to uncover crucial clues about the nature of mutation. Those methods also led to Muller's winning a Nobel prize for showing that X rays increased mutation rates.

The trick, Muller found, was to look fora more plentiful type of needle. He focused his efforts on lethal mutations, which he and Altenburg had shown to be much more common than the morphologicalmutants commonly studied at the time. Thefirst major test of their methods was to compare mutation rates in Drosophila at different temperatures. Muller found a small but statistically significant increase in mutation rate at higher temperatures. This was the first demonstration that mutation rates could be altered by an external influence.

As Muller was writing up a comprehensive account of these experiments, he started testing the effects of X rays on mutaCopyright tion rates. It became immediately apparent that radiation exposure massively increased mutation rates. And Muller's quantitative methods put hard numbers on the increase.

Muller raced off a cursory note to Science to establish priority, and the GENETICS article describing the methods development and temperature result was published the following year. As well as marking a new era in mutation studies, the GENETICS article kick-started this journal'slongtraditionof publishing foundational work that uses mutation rates to investigate the mechanisms of inheritance and evolution.

Communicating editor: M. F. Wolfner



The Measurement of Gene Mutation Rate in Drosophila, Its High Variability, and Its Dependence upon Temperature

Hermann Joseph Muller

Genetics July 1, 1928 13: 279-357


Further Reading in GENETICS

Carlson, E. A., 2011 Speaking out about the social implications of science: the uneven legacy of H. J. Muller. Genetics 187: 1-7.

Crow, J. F., 1995 Quarreling geneticists and a diplomat. Genetics 140: 421-426.

Crow, J. F., 2006 H. J. Muller and the "Competition Hoax." Genetics 173: 511-514.

Crow, J. F., and S. Abrahamson, 1997 Seventy years ago: mutation becomes experimental. Genetics 147: 1491-1496.

Drake, J. W., B. Charlesworth, D. Charlesworth, and J. F. Crow, 1998 Rates of spontaneous mutation. Genetics 148: 1667- 1686.

Gao, Z., D. Waggoner, M. Stephens, C. Ober, and M. Przeworski, 2015 An estimate of the average number of recessive lethal mutations carried by humans. Genetics 199: 1243-1254.

Houle, D., B. Morikawa, and M. Lynch, 1996 Comparing mutational variabilities. Genetics 143: 1467-1483.

Johnson, N. A., 2002 Sixty years after "Isolating Mechanisms, Evolution and Temperature": Muller's legacy. Genetics 161: 939-944.

Keightley, P. D., 2012 Rates and fitness consequences of new mutations in humans. Genetics 190: 295-304.

Lang, G. I., and A. W. Murray, 2008 Estimating the per-base-pair mutation rate in the yeast Saccharomyces cerevisiae. …

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