A Spotlight on Bacterial Mutations for 75 Years
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NEWS & VIEWS RESEARCH In Retrospect A spotlight on bacterial mutations for 75 years 50 Years Ago In the debate about how bacterial mutations arise, an experiment in 1943 showed that they can occur spontaneously and independently of a selection pressure. After the wreck of the Torrey This study also popularized the use of maths-driven analysis of biological data. Canyon in March 1967, some 8,000 seabirds were taken to cleansing stations in Britain — but MANOSHI S. DATTA & ROY KISHONY some difficulties when they entered the debate well under ten per cent … of these about how bacterial evolution occurs. To birds were rehabilitated and returned o bacteria acquire mutations establish an approach to study mutations in to the sea. Even this figure gives too randomly, or do mutations arise bacteria, they allowed individual Escherichia optimistic a picture of the cleansing adaptively as a direct response to coli cells to grow into large populations in indi- operation, for a large proportion of Denvironmental pressures? This question vidual test tubes, and added the cells from each the so-called rehabilitated birds were has wide implications in areas ranging from of these tubes to Petri dishes containing agar recovered dead within a few days. evolution to the treatment of bacterial infec- coated with viruses known to kill the bacteria. Although exact figures are hard to tions. In 1943, writing in Genetics, Luria and Luria and Delbrück monitored the number come by, the Torrey Canyon episode Delbrück1 revealed, by a combination of of visible bacterial colonies on each of the revealed the complete inadequacy of experimental analysis and profound math- plates. Each of these virus-resistant colonies the current methods of rehabilitating ematical insight, that bacteria evolve through arises from a cell and its descendants that had oiled birds … Legislation can never random mutations that arise independently a mutation enabling the cells to survive the totally eliminate accidental pollution of an environmental stress, and that occur viral attack. Yet, for a simple experiment, their and it is estimated that even the even before bacteria encounter such selective results were initially confusing: the number much vaunted “load on top” system conditions. Their study was a milestone in a of colonies was highly variable between the of washing tankers, although a great debate about the nature and causes of bacter- different plates, a result that the authors ini- improvement on previous practice, ial evolution that is still ongoing. Moreover, tially attributed to an experimental error (see produces pollution at a rate of this work has inspired the fields of microbial go.nature.com/2brojqp). But in a moment of 400,000 tons a year. evolution and quantitative biology. clarity, Luria realized7 that the high variability From Nature 30 November 1968 Luria and Delbrück worked at a time when in the number of bacterial colonies might be scientists disagreed on the fundamental nature an important clue, not an error. of bacterial evolution2, despite tremendous Let’s consider the experimental variance advances in molecular biology and micro- in the number of virus-resistant colonies per 100 Years Ago biology. For plants and animals, there was Petri dish expected under the process of either a general consensus that, consistent with adaptive or random mutation. If mutations [U]ndoubtedly the war has been Charles Darwin’s theory of evolution, natu- arise by an adaptive process, each bacterial responsible for an enormous ral selection acted on mutations that arose cell would have a chance of acquiring a resist- amount of destruction of capital; randomly, regardless of their benefit to the ance mutation only on encountering the virus. but when estimates are given … of organism. However, the unusual nature of bac- Assuming each cell’s chance of becoming resist- the percentage of loss in Belgium, terial genetics — such as the absence of sexual ant is small, the prediction would be that the France, Italy, Serbia and other reproduction — sparked a vigorous debate number of virus-resistant colonies per Petri countries, it is not usually borne in about whether the principles that drive animal dish would vary according to a Poisson distri- mind that capital does not merely evolution also apply to bacteria (see go.nature. bution (a standard probability distribution for consist of gold and silver, of bricks com/2brojqp). The main alternative hypothe- random events, in which the standard deviation and mortar … or even of railways, sis was Lamarckian evolution, named after the of the data equals the square root of the mean). steamships and machinery … but French biologist Jean-Baptiste Lamarck. In this But, if evolution is driven by random muta- of scientific knowledge … When, model, the specific mutations that provide an tions, mutations that confer viral resistance therefore, we compile estimates of advantage to an organism are acquired directly would arise during the growth of the bacterial the losses due to the war, let us not in response to the organism’s environment3 . population before viral exposure. In this case, forget that our greatest asset, the For present-day microbiologists, this debate the experimental variance in the number of vast store of knowledge that Science might seem strangely contrived — after all, if virus-resistant bacterial colonies between dif- has gathered together for us … is other organisms evolve in a manner consist- ferent Petri dishes would be much higher than still intact. It is a store that has slowly ent with the Darwinian principles of randomly in the adaptive-mutation scenario, because the been accumulating ever since the occurring organismal variation that selection number of virus-resistant bacteria in a given beginning of the world — a store can act on, why should bacteria be an excep- test tube would depend on the random timing which enables man more and more tion? Yet, it’s worth having sympathy for our of when mutations occurred. A single virus- to triumph over Nature, and one scientific predecessors. Even though we now resistance mutation that occurred early in that for ever remains practically accept that bacteria evolve through Darwinian the growth of the bacterial population would indestructible as the real permanent mechanisms, ‘quasi-Lamarckian’ processes of result in a large number of virus-resistant capital of the race, and by far its bacterial evolution are still being discovered bacterial descendants of the original mutated most precious heritage. and debated4–6. cell, whereas mutations that arose much later From Nature 28 November 1918 Luria and Delbrück themselves encountered during the growth of the bacterial culture, just ©2018 Spri nger Nature Li mited. All ri ghts reserved. ©2018 Spri nger Nature Li mited. All ri ghts reserv29ed. NOVEMBER 2018 | VOL 563 | NATURE | 633 RESEARCH NEWS & VIEWS before viral encounter, would produce many of antibiotic-resistant bacterial mutants before A fun challenge would be to repeat the fewer virus-resistant bacteria. treatment could improve our ability to predict Luria–Delbrück experiment under conditions On the basis of this insight, Luria and Del- treatment outcome. that might favour the evolution of resistance brück generated a statistical distribution (the Did the Luria and Delbrück study really by such adaptive mechanisms, for example by Luria–Delbrück distribution) to describe close the door on Lamarckism? As far as bac- replacing E. coli with S. thermophilus. Would the prevalence of virus-resistant bacterial teria are concerned, the answer is much more the distribution of the number of resistant mutants that would be expected if mutations complicated than the duo could probably ever mutants indicate random or adaptive muta- arose randomly before the bacterial popula- have anticipated. tions? What would Luria and Delbrück have tion came under selective pressure from the It is undeniable today that randomly concluded had they used a species that had virus. Compared with a Poisson distribution occurring mutations and natural selection the CRISPR–Cas system? The contingency of expected for adaptive mutations, this Luria– are central tenets of how bacterial evolution this historic choice underscores the fact that, Delbrück distribution has a long ‘tail’ at the occurs5. However, scientists are uncovering like evolution, science perhaps also progresses end of the distribution pattern. In the context and debating an increasing array of other both adaptively and randomly. ■ of the authors’ experiments, this tail would evolutionary processes at work in bacteria, correspond to Petri dishes that have a high some of which are suspiciously Lamarckian Manoshi S. Datta and Roy Kishony are number of bacterial colonies, corresponding in character4–6. For example, we now know in the Faculty of Biology, Technion–Israel to early mutational events that lead to a large that the genome-wide mutation rate, and Institute of Technology, Haifa 3200003, Israel. number of mutant descendants. even the mutation rates of specific genes, e-mails: [email protected]; The 1943 paper reported the results of the can be shaped by evolution and affected by [email protected] authors’ experiments, termed fluctuation the environment13–15. An even more striking 1. Luria, S. E. & Delbrück, M. Genetics 28, 491–511 tests, that took this mathematical approach example is bacterial adaptation through the (1943). to analyse the number of virus-resistant CRISPR–Cas viral-defence system, in which 2. Zheng, Q. Chance 23 (2), 15–18 (2010). colonies in E. coli populations. The authors’ bacteria can incorporate viral genetic material 3. Lenski, R. E. PLoS Genet. 13, e1006668 (2017). 4. Koonin, E. V. & Wolf, Y. I. Biol. Direct 4, 42 (2009). findings were consistent with mutations fol- into their own genomes and use it, as an adap- 5. Sniegowski, P. D. & Lenski, R. E. Annu. Rev. Ecol. Syst. lowing a Luria–Delbrück distribution rather tive mechanism, to protect themselves and 26, 553–578 (1995). than a Poisson distribution, demonstrating their descendants against current and subse- 6.