clonal interference
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Clonal interference is a phenomenon in evolutionary biology, related to the
population genetics Population genetics is a subfield of genetics that deals with genetic differences within and between populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and pop ...
of organisms with significant
linkage disequilibrium In population genetics, linkage disequilibrium (LD) is the non-random association of alleles at different loci in a given population. Loci are said to be in linkage disequilibrium when the frequency of association of their different alleles is h ...
, especially asexually reproducing organisms. The idea of clonal interference was introduced by American geneticist
Hermann Joseph Muller Hermann Joseph Muller (December 21, 1890 – April 5, 1967) was an American geneticist, educator, and Nobel laureate best known for his work on the physiological and genetic effects of radiation (mutagenesis), as well as his outspoken political ...
in 1932. It explains why beneficial
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s can take a long time to get fixated or even disappear in asexually reproducing populations. As the name suggests, clonal interference occurs in an asexual lineage ("clone") with a beneficial mutation. This mutation would be likely to get fixed if it occurred alone, but it may fail to be fixed, or even be lost, if another beneficial-mutation lineage arises in the same population; the multiple clones interfere with each other.


Mechanism of clonal interference

Whenever a beneficial mutation arises in a population, for example mutation A, the carrier of the mutation obtains a higher fitness compared to members of the population without mutation A by means of
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charle ...
. In the absence of
genetic recombination Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryo ...
(i.e. in asexually reproducing organisms) this beneficial mutation is only present in the clones of the cell in which the mutation arose. Because of this, the relative frequency of mutation A only increases slowly over time. In large asexually reproducing populations, it can take a long time before the mutation is fixated. In this time, another beneficial mutation, for example mutation B, can arise independently in another individual of the population. Mutation B also increases the fitness of the carrier. In this context, mutation A is often referred to as the ‘original mutation’, whereas mutation B is referred to as the ‘alternative’ or ‘interfering’ mutation. In sexually reproducing populations, both carriers of mutations A and B have a higher fitness and therefore a bigger chance to survive and to produce offspring. When a carrier of mutation A produces offspring with a carrier of mutation B, the more-fit genotype AB can arise. Individuals with genotype AB once again have a higher fitness and therefore they are likely to produce more offspring, assuming that there is no negative interaction between the two mutations. In this way, the relative frequency of both mutation A and B can increase rapidly and both can be fixated simultaneously in the population. This allows evolution to proceed more rapidly, a phenomenon known as the Hill-Robertson effect. On the contrary, in asexually reproducing populations, beneficial mutations A and B cannot (easily) be combined into a single more-fit genotype AB because of the absence of the genetic recombination. Therefore, carriers of mutation A and carriers of mutation B will compete against each other. This typically leads to the loss of one of them, confirming that the fate of an advantageous mutation can be determined by other mutations present in the same population.


Implications of clonal interference on adaptivity

When Muller introduced the phenomenon of clonal interference, he used it to explain why sexual reproduction evolved. He reasoned that the loss of beneficial mutations because of clonal interference inhibits the adaptivity of asexually reproducing species. Sex and other reproductive strategies involving recombination would therefore be evolutionary advantageous according to Muller. From the 1970’s however, biologists have demonstrated that asexually and sexually reproducing strategies yield the same rate of the evolutionary adaptivity. This has to do with the fact that clonal interference also influences another part of the reproductive strategy of a population, namely mutation rate. Clonal interference does not only play a role in the fixation of mutations in chromosomal DNA, but it also influences the stability or persistence of extrachromosomal DNA in the form of
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s. Plasmids often carry genes that code for traits like antibiotic resistance. Because of this, bacteria can become resistant to antibiotics in absence of genes coding for this trait in their chromosomal DNA. However, plasmids are not always adapted to their host cell, often resulting in the loss of the plasmid during
cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
. In this way, the relative frequency of carriers of this plasmid in a population can decline. However, also in these plasmids mutations can occur, resulting in competition between carriers of the plasmids. Because of this competition, the most stable plasmids will eventually get selected for and their frequency within the population will increase. In this way, clonal interference influences the evolutionary dynamics of plasmid-host adaptation, resulting in faster stabilisation of plasmids in a population.


Clinical implications and applications

The phenomenon of clonal interference also occurs in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
and pre-cancer cell lineages within a patient. The heterogeneity found in cells of carcinogenic tumours implies competition between sub-populations of cells in the tumour, hence clonal interference. Population dynamics within cancer lineages are therefore becoming of increasing importance in the clinical research on cancer treatments. Furthermore, knowledge on the role of population dynamics and clonal interference, often resulting in antibiotic resistance, is being taken into account in the treatment of infectious diseases with antibiotics.


See also

*
Evolutionary biology Evolutionary biology is the subfield of biology that studies the evolutionary processes (natural selection, common descent, speciation) that produced the diversity of life on Earth. It is also defined as the study of the history of life fo ...
* Hill-Robertson effect


References

{{Reflist, 30em Population genetics