Proteins are trans-acting but sites on DNA are cis-acting

KEY TERMS:

• cis configuration describes two sites on the same molecule of DNA.
• trans configuration of two sites refers to their presence on two different molecules of DNA (chromosomes).
• A cis-acting site affects the activity only of sequences on its own molecule of DNA (or RNA); this property usually implies that the site does not code for protein.

KEY CONCEPTS:

• All gene products (RNA or proteins) are trans-acting. They can act on any copy of a gene in the cell.
• cis-acting mutations identify sequences of DNA that are targets for recognition by trans-acting products. They are not expressed as RNA or protein and affect only the contiguous stretch of DNA.  

A crucial step in the definition of the gene was the realization that all its parts must be present on one contiguous stretch of DNA. In genetic terminology, sites that are located on the same DNA are said to be in cis. Sites that are located on two different molecules of DNA are described as being in trans. So two mutations may be in cis (on the same DNA) or in trans (on different DNAs). The complementation test uses this concept to determine whether two mutations are in the same gene (see Figure 1.27 in 1.16 Mutations in the same gene cannot complement). We may now extend the concept of the difference between cis and trans effects from defining the coding region of a gene to describing the interaction between regulatory elements and a gene.

Suppose that the ability of a gene to be expressed is controlled by a protein that binds to the DNA close to the coding region. In the example depicted in Figure 1.40, messenger RNA can be synthesized only when the protein is bound to the DNA. Now suppose that a mutation occurs in the DNA sequence to which this protein binds, so that the protein can no longer recognize the DNA. As a result, the DNA can no longer be expressed.

So a gene can be inactivated either by a mutation in a control site or by a mutation in a coding region. The mutations cannot be distinguished genetically, because both have the property of acting only on the DNA sequence of the single allele in which they occur. They have identical properties in the complementation test, and a mutation in a control region is therefore defined as comprising part of the gene in the same way as a mutation in the coding region.

Figure 1.41 shows that a deficiency in the control site affects only the coding region to which it is connected; it does not affect the ability of the other allele to be expressed. A mutation that acts solely by affecting the properties of the contiguous sequence of DNA is called cis-acting.

We may contrast the behavior of the cis-acting mutation shown in Figure 1.41 with the result of a mutation in the gene coding for the regulator protein. Figure 1.42 shows that the absence of regulator protein would prevent both alleles from being expressed. A mutation of this sort is said to be trans-acting.

Reversing the argument, if a mutation is trans-acting, we know that its effects must be exerted through some diffusible product (typically a protein) that acts on multiple targets within a cell. But if a mutation is cis-acting, it must function via affecting directly the properties of the contiguous DNA, which means that it is not expressed in the form of RNA or protein.