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
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
, implying that organisms can respond to environmental stresses by directing mutations to certain
genes or areas of the
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
. There have been a wide variety of experiments trying to support (or disprove) the idea of adaptive mutation, at least in
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s.
Definition
The most widely accepted theory of
evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
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.
This theory of adaptive mutation was first brought to academic attention in the 1980s by
John Cairns.
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,
responses to starvation in ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'',
and testing for revertants of a
tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
auxotroph
Auxotrophy ( grc, αὐξάνω "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this ...
in ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'' (yeast).
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.
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.
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
The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...
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.
Adaptive mutation was re-proposed in 1988 by
John Cairns who was studying ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' that lacked the ability to
metabolize
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
lactose. He grew these bacteria in
media
Media may refer to:
Communication
* Media (communication), tools used to deliver information or data
** Advertising media, various media, content, buying and placement for advertising
** Broadcast media, communications delivered over mass e ...
in which lactose was the only source of
energy
In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of hea ...
. In doing so, he found that the rate at which the bacteria
evolved
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
the ability to metabolize lactose was many
orders of magnitude
An order of magnitude is an approximation of the logarithm of a value relative to some contextually understood reference value, usually 10, interpreted as the base of the logarithm and the representative of values of magnitude one. Logarithmic dis ...
higher than would be expected if the
mutations were truly
random
In common usage, randomness is the apparent or actual lack of pattern or predictability in events. A random sequence of events, symbols or steps often has no order and does not follow an intelligible pattern or combination. Individual ra ...
. This inspired him to propose that the mutations that had occurred had been ''directed'' at those genes involved in lactose utilization.
Later support for this hypothesis came from Susan Rosenberg, then at the
University of Alberta
The University of Alberta, also known as U of A or UAlberta, is a Public university, public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford,"A Gentleman of Strathcona – Alexande ...
, who found that an enzyme involved in
DNA recombinational repair,
recBCD
Exodeoxyribonuclease V (EC 3.1.11.5, RecBCD, Exonuclease V, ''Escherichia coli'' exonuclease V, ''E. coli'' exonuclease V, gene recBC endoenzyme, RecBC deoxyribonuclease, gene recBC DNase, gene recBCD enzymes) is an enzyme of ''E. coli'' that ini ...
, 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
Darwinism is a theory of biological evolution developed by the English naturalist Charles Darwin (1809–1882) and others, stating that all species of organisms arise and develop through the natural selection of small, inherited variations that ...
process. 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".
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
The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis is induced. The system involves the RecA protein (Rad51 in eukaryotes). The RecA protein, stimulated by single-stranded DNA ...
in ''E. coli'' is a response to DNA damage that must be repaired. The normal
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
is put on hold and
mutagenesis
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 lab ...
may begin. This means that mutations will occur to try to fix the damage. This
hypermutation
Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM div ...
, or increased rate of change, response has to have some regulatory process, and some key molecules in this process are
RecA
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 homolog ...
, and
LexA
Repressor LexA or LexA is a transcriptional repressor () that represses SOS response genes coding primarily for error-prone DNA polymerases, DNA repair enzymes and cell division inhibitors. LexA forms ''de facto'' a two-component regulatory system ...
. 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.
Yeast
Dr. von Borstel, in the 1970s, conducted experiments similar to the Lactose Starvation experiment with yeast, specifically ''Saccharomyces cerevisiae''. He tested for tryptophan
auxotroph
Auxotrophy ( grc, αὐξάνω "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this ...
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
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...
revertants, or Steele & Jinks-Robertson who tested
lysine. These experiments demonstrate how
recombination and
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
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.
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 & Jinks-Robertso
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
''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
.''
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.
References
{{Reflist
Mutation
Non-Darwinian evolution