Genetic Selection

Selection is the process by which organisms with certain traits gain reproductive advantage over organisms of the same population without those traits. Provided that the traits are heritable, selection increases the prevalence of the selected traits in the population, ie, the population becomes adapted to the selective conditions. The source of heritable variation is mutation, so selection is the differential reproduction of mutant individuals. Selection has somewhat different connotations depending on whether it is used in a genetic sense or in an evolutionary sense.

In genetic usage, selection almost always means allowing only individuals with a given trait, usually mutants, to reproduce. Thus, selection allows the researcher to isolate an extremely rare mutant so long as the mutant has a selectable phenotype. A common example is antibiotic resistance in bacteria, which is caused by a mutation or the acquisition of a plasmid or transposable element carrying drug resistance. In the presence of the antibiotic, the resistant bacteria survive and give rise to clones of resistant progeny, whereas sensitive bacteria are killed. Likewise, with the proper selection, rare cells or organisms with other desirable characteristics can be harvested from a large population. Typical genetic selections are for amino acid prototrophies, for the use of specific carbon sources or for suppression of a conditional lethal mutation. The unwanted individuals do not have to die, but only fail to reproduce.

Selection is distinguished from two other genetic manipulations, enrichment and screening. Enrichment is also a selective process, but unwanted individuals do not fail to reproduce. Typically, several rounds of enrichment for growth on a poorly used substrate, for example, are needed to obtain a reasonably pure culture of mutant cells better able to use the substrate. Screens, on the other hand, are nonselective but allow the researcher to identify the desired cell or organism. For example, a typical step in cloning a gene is to insert it into a plasmid so that another gene, for which an easy assay exists, is disrupted. Genes are commonly cloned into the lacZ gene, which encodes beta-galactosidase. Cells with active b-galactosidase turn blue on medium containing X-gal (5-bromo-4-chloro-3-indolyl-b-D-galactopyranoside), so the progeny of cells receiving the disrupted lacZ gene containing the cloned gene are white and can be isolated for further analysis.

 Selections are often devised to find cells that have gained a trait, whereas screens must usually be used to identify cells that have lost a trait. But there are notable exceptions. For example, mutations that inactivate nonessential genes are selected with toxic analogues of the normal enzyme's substrate. And part of the intellectual challenge of genetics is to devise selection procedures to find desired genes or proteins. Recently, the yeast two-hybrid system for identifying interacting proteins has been used to select for inactivating mutations by making a successful interaction toxic to the cell (1).

In evolutionary usage, selection is the process by which adaptive changes take place in populations over time. Natural selection increases the mean fitness of a population by enriching it for more fit individuals and decreasing the prevalence of less fit individuals, thus producing changes in the frequencies of the genetic alleles associated with variation in fitness. There are two ways in which fitness is measured: (1) the number of offspring an individual produces; and (2) the change in the frequency of a certain allele with time. Because selection operates on the whole organism, the first of these has more evolutionary meaning. However, an organism's phenotype is the totality of its traits, each of which may or may not contribute to its fitness. Selection operates to favor particular traits encoded by particular genetic alleles. While this is what is usually meant by evolution, it is not necessarily true that all of the traits of a population are adaptive. Neutral genetic alleles can become prevalent in a population by chance, a process known as genetic drift.

 Although fitness can be measured absolutely, a more meaningful measure is relative fitness, i.e., the fitness of individuals with a particular genotype relative to individuals with another genotype. The strength of the selective pressure on individuals with a given genotype, the selection coefficient, is one minus their relative fitness. Note that the selective pressure can be positive or negative, but because the fittest genotype is usually given the value of 1, the selection coefficient takes values of 0

to 1. Negative selection eliminates variants from the population, whereas positive selection favors them. Fitness can be defined only for a given set of conditions. Today's fittest genotype may be at a disadvantage if conditions change.

References

1. M. Vidal, R. K. Brachmann, A. Fattaey, E. Harlow, and J. D. Boeke (1996) Proc. Natl. Acad. Sci. USA 93, 10315–10320.