Adaptive mutation

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Adaptive mutation, also called directed mutation or directed mutagenesis is a controversial evolutionary theory. It posits that mutations, or genetic changes, are much less random and more purposeful than traditional evolution, implying that organisms can respond to environmental stresses by directing mutations to certain genes or areas of the genome. There have been a wide variety of experiments trying to support (or disprove) the idea of adaptive mutation, at least in microorganisms.

Contents

Definition

The most widely accepted theory of evolution states that organisms are modified by natural selection where changes caused by mutations improve their chance of reproductive success. Adaptive mutation states that rather than mutations and evolution being random, they are in response to specific stresses. In other words, the mutations that occur are more beneficial and specific to the given stress, instead of random and not a response to anything in particular. The term stress refers to any change in the environment, such as temperature, nutrients, population size, etc. Tests with microorganisms have found that for adaptive mutation, more of the mutations observed after a given stress were more effective at dealing with the stress than chance alone would suggest is possible. [1] [2] This theory of adaptive mutation was first brought to academic attention in the 1980s by John Cairns. [3]

Recent studies

Adaptive mutation is a controversial claim leading to a series of experiments designed to test the idea. Three major experiments are the SOS response, [4] responses to starvation in Escherichia coli , [5] and testing for revertants of a tryptophan auxotroph in Saccharomyces cerevisiae (yeast). [1]

Lactose starvation

The E. coli strain FC40 has a high rate of mutation, and so is useful for studies, such as for adaptive mutation. Due to a frameshift mutation, a change in the sequence that causes the DNA to code for something different, FC40 is unable to process lactose. When placed in a lactose-rich medium, it has been found that 20% of the cells mutated from Lac- (could not process lactose) to Lac+, meaning they could now utilize the lactose in their environment. The responses to stress are not in current DNA, but the change is made during DNA replication through recombination and the replication process itself, meaning that the adaptive mutation occurs in the current bacteria and will be inherited by the next generations because the mutation becomes part of the genetic code in the bacteria. [5] This is particularly obvious in a study by Cairns, which demonstrated that even after moving E. coli back to a medium with minimal levels of lactose, Lac+ mutants continued to be produced as a response to the previous environment. [1] This would not be possible if adaptive mutation was not at work because natural selection would not favor this mutation in the new environment. Although there are many genes involved in adaptive mutation, RecG, a protein, was found to have an effect on adaptive mutation. By itself, RecG was found to not necessarily lead to a mutational phenotype. However, it was found to inhibit the appearance of revertants (cells that appeared normally, as opposed to those with the mutations being studied) in wild type cells. On the other hand, RecG mutants were key to the expression of RecA-dependent mutations, which were a major portion of study in the SOS response experiments, such as the ability to utilize lactose. [6]

Adaptive mutation was re-proposed in 1988 [7] by John Cairns who was studying Escherichia coli that lacked the ability to metabolize lactose. He grew these bacteria in media in which lactose was the only source of energy. In doing so, he found that the rate at which the bacteria evolved the ability to metabolize lactose was many orders of magnitude higher than would be expected if the mutations were truly random. This inspired him to propose that the mutations that had occurred had been directed at those genes involved in lactose utilization. [8]

Later support for this hypothesis came from Susan Rosenberg, then at the University of Alberta, who found that an enzyme involved in DNA recombinational repair, recBCD, was necessary for the directed mutagenesis observed by Cairns and colleagues in 1989. The directed mutagenesis hypothesis was challenged in 2002, by work showing that the phenomenon was due to general hypermutability due to selected gene amplification, followed by natural selection, and was thus a standard Darwinian process. [9] [10] Later research from 2007 however, concluded that amplification could not account for the adaptive mutation and that "mutants that appear during the first few days of lactose selection are true revertants that arise in a single step". [11]

SOS response

This experiment is different from the others in one small way: this experiment is concerned with the pathways leading to an adaptive mutation while the others tested the changing environment microorganisms were exposed to. The SOS response in E. coli is a response to DNA damage that must be repaired. The normal cell cycle is put on hold and mutagenesis may begin. This means that mutations will occur to try to fix the damage. This hypermutation, or increased rate of change, response has to have some regulatory process, and some key molecules in this process are RecA, and LexA. These are proteins and act as stoplights for this and other processes. They also appear to be the main contributors to adaptive mutation in E. coli. Changes in presence of one or the other was shown to affect the SOS response, which in turn affected how the cells were able to process lactose, which should not be confused with the lactose starvation experiment. The key point to understand here is that LexA and RecA both were required for adaptive mutation to occur, and without the SOS response adaptive mutation would not be possible. [1]

Yeast

von Borstel, in the 1970s, conducted experiments similar to the Lactose Starvation experiment with yeast, specifically Saccharomyces cerevisiae. He tested for tryptophan auxotroph revertants. A tryptophan auxotroph cannot make tryptophan for itself, but wild-type cells can and so a revertant will revert to the normal state of being able to produce tryptophan. He found that when yeast colonies were moved from a tryptophan-rich medium to a minimal one, revertants continued to appear for several days. The degree to which revertants were observed in yeast was not as high as with bacteria. Other scientists have conducted similar experiments, such as Hall who tested histidine revertants, or Steele and Jinks-Robertson who tested lysine. These experiments demonstrate how recombination and DNA replication are necessary for adaptive mutation. However, in lysine-tested cells, recombination continued to occur even without selection for it. Steele and Jinks-Robertson concluded that recombination occurred in all circumstances, adaptive or otherwise, while mutations were present only when they were beneficial and adaptive. [1]

Although the production of mutations during selection was not as vigorous as observed with bacteria, these studies are convincing. As mentioned above, a subsequent study adds even more weight to the results with lys2. Steele and Jinks-Robertson [12] found that LYS prototrophs due to interchromosomal recombination events also continue to arise in nondividing cells, but in this case, the production of recombinants continued whether there was selection for them or not. Thus, mutation occurred in stationary phase only when it was adaptive, but recombination occurred whether it was adaptive or not.

Delayed appearance of mutants has also been reported for Candida albicans . [13] With long exposure to sublethal concentrations of heavy metals, colonies of resistant cells began to appear after 5–10 days and continued to appear for 1–2 weeks thereafter. These resistances could have resulted from gene amplification, although the phenotypes were stable during a short period of nonselective growth. However, revertants of two auxotrophies also appeared with similar kinetics. None of these events in Candida albicans have, as yet, been shown to be specific to the selection imposed.

Related Research Articles

Mutagenesis is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. A mutagen is a mutation-causing agent, be it chemical or physical, which results in an increased rate of mutations in an organism's genetic code. In nature mutagenesis can lead to cancer and various heritable diseases, and it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century.

Protein engineering is the process of developing useful or valuable proteins through the design and production of unnatural polypeptides, often by altering amino acid sequences found in nature. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles. It has been used to improve the function of many enzymes for industrial catalysis. It is also a product and services market, with an estimated value of $168 billion by 2017.

<span class="mw-page-title-main">Molecular genetics</span> Scientific study of genes at the molecular level

Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. 

<i>lac</i> operon Set genes encoding proteins and enzymes for lactose metabolism

The lactose operon is an operon required for the transport and metabolism of lactose in E. coli and many other enteric bacteria. Although glucose is the preferred carbon source for most enteric bacteria, the lac operon allows for the effective digestion of lactose when glucose is not available through the activity of beta-galactosidase. Gene regulation of the lac operon was the first genetic regulatory mechanism to be understood clearly, so it has become a foremost example of prokaryotic gene regulation. It is often discussed in introductory molecular and cellular biology classes for this reason. This lactose metabolism system was used by François Jacob and Jacques Monod to determine how a biological cell knows which enzyme to synthesize. Their work on the lac operon won them the Nobel Prize in Physiology in 1965.

<span class="mw-page-title-main">SOS response</span> Biological process

The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis are induced. The system involves the RecA protein. The RecA protein, stimulated by single-stranded DNA, is involved in the inactivation of the repressor (LexA) of SOS response genes thereby inducing the response. It is an error-prone repair system that contributes significantly to DNA changes observed in a wide range of species.

<span class="mw-page-title-main">Auxotrophy</span> Inability to synthesize an organic compound required for growth

Auxotrophy is the inability of an organism to synthesize a particular organic compound required for its growth. An auxotroph is an organism that displays this characteristic; auxotrophic is the corresponding adjective. Auxotrophy is the opposite of prototrophy, which is characterized by the ability to synthesize all the compounds needed for growth.

<span class="mw-page-title-main">DNA repair</span> Cellular mechanism

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or cancer as per the two-hit hypothesis.

RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.

<span class="mw-page-title-main">Luria–Delbrück experiment</span> 1943 experiment into rate of mutations

The Luria–Delbrück experiment (1943) demonstrated that in bacteria, genetic mutations arise in the absence of selective pressure rather than being a response to it. Thus, it concluded Darwin's theory of natural selection acting on random mutations applies to bacteria as well as to more complex organisms. Max Delbrück and Salvador Luria won the 1969 Nobel Prize in Physiology or Medicine in part for this work.

<span class="mw-page-title-main">RecA</span> DNA repair protein

RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA. A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins. The homologous protein is called RAD51 in eukaryotes and RadA in archaea.

<span class="mw-page-title-main">Directed evolution</span> Protein engineering method

Directed evolution (DE) is a method used in protein engineering that mimics the process of natural selection to steer proteins or nucleic acids toward a user-defined goal. It consists of subjecting a gene to iterative rounds of mutagenesis, selection and amplification. It can be performed in vivo, or in vitro. Directed evolution is used both for protein engineering as an alternative to rationally designing modified proteins, as well as for experimental evolution studies of fundamental evolutionary principles in a controlled, laboratory environment.

Recombineering is a genetic and molecular biology technique based on homologous recombination systems, as opposed to the older/more common method of using restriction enzymes and ligases to combine DNA sequences in a specified order. Recombineering is widely used for bacterial genetics, in the generation of target vectors for making a conditional mouse knockout, and for modifying DNA of any source often contained on a bacterial artificial chromosome (BAC), among other applications.

<span class="mw-page-title-main">Blue–white screen</span> DNA screening technique

The blue–white screen is a screening technique that allows for the rapid and convenient detection of recombinant bacteria in vector-based molecular cloning experiments. This method of screening is usually performed using a suitable bacterial strain, but other organisms such as yeast may also be used. DNA of transformation is ligated into a vector. The vector is then inserted into a competent host cell viable for transformation, which are then grown in the presence of X-gal. Cells transformed with vectors containing recombinant DNA will produce white colonies; cells transformed with non-recombinant plasmids grow into blue colonies.

The phage group was an informal network of biologists centered on Max Delbrück that contributed heavily to bacterial genetics and the origins of molecular biology in the mid-20th century. The phage group takes its name from bacteriophages, the bacteria-infecting viruses that the group used as experimental model organisms. In addition to Delbrück, important scientists associated with the phage group include: Salvador Luria, Alfred Hershey, Seymour Benzer, Charles Steinberg, Gunther Stent, James D. Watson, Frank Stahl, and Renato Dulbecco.

<span class="mw-page-title-main">Evelyn M. Witkin</span> American geneticist (1921–2023)

Evelyn M. Witkin was an American bacterial geneticist at Cold Spring Harbor Laboratory (1944–1955), SUNY Downstate Medical Center (1955–1971), and Rutgers University (1971–1991). Witkin was considered innovative and inspirational as a scientist, teacher and mentor.

<i>E. coli</i> long-term evolution experiment Scientific study

The E. coli long-term evolution experiment (LTEE) is an ongoing study in experimental evolution begun by Richard Lenski at the University of California, Irvine, carried on by Lenski and colleagues at Michigan State University, and currently overseen by Jeffrey E. Barrick at the University of Texas at Austin. It has been tracking genetic changes in 12 initially identical populations of asexual Escherichia coli bacteria since 24 February 1988. Lenski performed the 10,000th transfer of the experiment on March 13, 2017. The populations reached over 73,000 generations in early 2020, shortly before being frozen because of the COVID-19 pandemic. In September 2020, the LTEE experiment was resumed using the frozen stocks.

<span class="mw-page-title-main">SOS chromotest</span>

The SOS chromotest is a biological assay to assess the genotoxic potential of chemical compounds. The test is a colorimetric assay which measures the expression of genes induced by genotoxic agents in Escherichia coli, by means of a fusion with the structural gene for β-galactosidase. The test is performed over a few hours in columns of a 96-well microplate with increasing concentrations of test samples. This test was developed as a practical complement or alternative to the traditional Ames test assay for genotoxicity, which involves growing bacteria on agar plates and comparing natural mutation rates to mutation rates of bacteria exposed to potentially mutagenic compounds or samples. The SOS chromotest is comparable in accuracy and sensitivity to established methods such as the Ames test and is a useful tool to screen genotoxic compounds, which could prove carcinogenic in humans, in order to single out chemicals for further in-depth analysis.

DNA Polymerase V is a polymerase enzyme involved in DNA repair mechanisms in bacteria, such as Escherichia coli. It is composed of a UmuD' homodimer and a UmuC monomer, forming the UmuD'2C protein complex. It is part of the Y-family of DNA Polymerases, which are capable of performing DNA translesion synthesis (TLS). Translesion polymerases bypass DNA damage lesions during DNA replication - if a lesion is not repaired or bypassed the replication fork can stall and lead to cell death. However, Y polymerases have low sequence fidelity during replication. When the UmuC and UmuD' proteins were initially discovered in E. coli, they were thought to be agents that inhibit faithful DNA replication and caused DNA synthesis to have high mutation rates after exposure to UV-light. The polymerase function of Pol V was not discovered until the late 1990s when UmuC was successfully extracted, consequent experiments unequivocally proved UmuD'2C is a polymerase. This finding lead to the detection of many Pol V orthologs and the discovery of the Y-family of polymerases.

No-SCAR genome editing is an editing method that is able to manipulate the Escherichia coli genome. The system relies on recombineering whereby DNA sequences are combined and manipulated through homologous recombination. No-SCAR is able to manipulate the E. coli genome without the use of the chromosomal markers detailed in previous recombineering methods. Instead, the λ-Red recombination system facilitates donor DNA integration while Cas9 cleaves double-stranded DNA to counter-select against wild-type cells. Although λ-Red and Cas9 genome editing are widely used technologies, the no-SCAR method is novel in combining the two functions; this technique is able to establish point mutations, gene deletions, and short sequence insertions in several genomic loci with increased efficiency and time sensitivity.

<span class="mw-page-title-main">Illegitimate recombination</span>

Illegitimate recombination, or nonhomologous recombination, is the process by which two unrelated double stranded segments of DNA are joined. This insertion of genetic material which is not meant to be adjacent tends to lead to genes being broken causing the protein which they encode to not be properly expressed. One of the primary pathways by which this will occur is the repair mechanism known as non-homologous end joining (NHEJ).

References

  1. 1 2 3 4 5 Foster, Patricia L. (1993). "Adaptive mutation: The uses of adversity". Annual Review of Microbiology. 47: 467–504. doi:10.1146/annurev.mi.47.100193.002343. PMC   2989722 . PMID   8257106.
  2. ↑ Sniegowski, P. D.; Lenski, R. E. (1995). "Mutation and adaptation: The directed mutation controversy in evolutionary perspective". Annual Review of Ecology and Systematics. 26: 553–578. doi:10.1146/annurev.es.26.110195.003005. JSTOR   2097219. S2CID   42252134.[ permanent dead link ]
  3. ↑ Cairns, J; Overbaugh, J.; Miller, S (1988). "The origin of mutants". Nature. 335 (6186): 142–45. Bibcode:1988Natur.335..142C. doi:10.1038/335142a0. PMID   3045565. S2CID   4304995.
  4. ↑ McKenzie, G.J.; Harris, R.S.; Lee, P.L.; Rosenberg, S.M. (2000). "The SOS response regulates adaptive mutation". Proceedings of the National Academy of Sciences of the United States of America. 97 (12): 6646–6651. Bibcode:2000PNAS...97.6646M. doi: 10.1073/pnas.120161797 . PMC   18688 . PMID   10829077.
  5. 1 2 Foster, Patricia L. (2000). "Adaptive mutation: implications for evolution". BioEssays. 22 (12): 1067–1074. doi:10.1002/1521-1878(200012)22:12<1067::AID-BIES4>3.0.CO;2-Q. PMC   2929355 . PMID   11084622.
  6. ↑ Foster, Patricia L.; Trimarchi, J.M.; Maurer, R.A. (1996). "Two enzymes, both of which process recombination intermediates, have opposite effects on adaptive mutation in Escherichia coli". Genetics. 142 (1): 25–37. doi:10.1093/genetics/142.1.25. PMC   1206954 . PMID   8770582.
  7. ↑ Cairns, J.; Overbaugh, J.; Miller, S. (September 1988). "The origin of mutants". Nature. 335 (6186): 142–5. Bibcode:1988Natur.335..142C. doi:10.1038/335142a0. PMID   3045565. S2CID   4304995.
  8. ↑ Symonds, N. (21 September 1991). "A fitter theory of evolution?: Biologists have always denied that organisms can adapt their genes to suit a new environment. But some startling discoveries about bacteria are making them think again". New Scientist . No. 1787. pp. 30–.
    Concar, D. (21 September 1991). "A fitter theory of evolution?". New Scientist. No. 1787. p. 30.
  9. ↑ Slechta, E. Susan; Liu, Jing; Andersson, Dan I.; Roth, John R. (1 July 2002). "Evidence That Selected Amplification of a Bacterial lac Frameshift Allele Stimulates Lac+ Reversion (Adaptive Mutation) With or Without General Hypermutability". Genetics. 161 (3): 945–956. doi:10.1093/genetics/161.3.945. PMC   1462195 . PMID   12136002.
  10. ↑ Slechta, E. Susan; Harold, Jennifer; Andersson, Dan I.; Roth, John R. (1 May 2002). "The effect of genomic position on reversion of a lac frameshift mutation (lacIZ33) during non-lethal selection (adaptive mutation)". Molecular Microbiology. 44 (4): 1017–1032. doi: 10.1046/j.1365-2958.2002.02934.x . PMID   12010495.
  11. ↑ Stumpf, Jeffrey D.; Poteete, Anthony R.; Foster, Patricia L. (2007-03-15). "Amplification of lac Cannot Account for Adaptive Mutation to Lac+ in Escherichia coli". Journal of Bacteriology. 189 (6): 2291–2299. doi:10.1128/JB.01706-06. PMC   1899370 . PMID   17209030.
  12. ↑ Foster, P. L. (1993). "ADAPTIVE MUTATION: The Uses of Adversity". Annual Review of Microbiology. 47: 467–504. doi:10.1146/annurev.mi.47.100193.002343. PMC   2989722 . PMID   8257106.
  13. ↑ Malavasic, M. J.; Cihlar, R. L. (1992). "Growth response of several Candida albicans strains to inhibitory concentrations of heavy metals". Journal of Medical and Veterinary Mycology. 30 (6): 421–32. doi:10.1080/02681219280000581.
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