The terms cis and trans are Latin prefixes describing relative physical location. Cis translates to “on this side,” while trans means “across from” or “on the other side of.” In genetics, these directional terms classify molecular components and their actions based on whether they are physically located on the same molecule or chromosome as their target, or if they originate from a separate location. This distinction applies across various genetic mechanisms, from gene regulation to the physical arrangement of linked genes.
Understanding the Foundational Difference
The core difference between cis and trans in biology is rooted in their spatial relationship to a target molecule. While initially used in chemistry to describe the arrangement of atoms, their utility was adapted to molecular biology. In genetics, a factor is considered cis-acting if it affects a function on the same piece of DNA or chromosome where it is physically located. This means the factor and its target are inextricably linked.
Conversely, a trans-acting factor affects a target located across space, often requiring it to be a diffusible molecule that can travel. This diffusibility allows a trans factor to be encoded by a gene on one chromosome, yet regulate a gene on an entirely different chromosome or region. The trans factor acts as a messenger, enabling communication across the nuclear space to influence a distant genetic element. Therefore, the cis factor is a fixed location or sequence, while the trans factor is a mobile agent.
Regulatory Elements and Diffusible Factors
The distinction between cis and trans is most significant in the study of gene expression, as it categorizes the components that control when and how much a gene is turned on. Cis-acting regulatory elements are specific DNA sequences that must be physically present on the same DNA molecule as the gene they regulate. These sequences act as binding sites and include elements like promoters, enhancers, and silencers.
The promoter is a sequence located upstream of a gene that serves as the initial attachment point for the transcription machinery. Enhancers are other sequences that can be located thousands of base pairs away, but they still act in cis because they must physically loop around to influence the gene on the same DNA strand. These elements are like the address and security codes of the gene, defining where and how regulatory molecules should interact. Because they are part of the DNA sequence, they cannot diffuse away to regulate a gene on another chromosome.
The control of these cis elements is executed by Trans-acting factors, which are typically proteins (like transcription factors) or sometimes RNA molecules. These factors are synthesized from genes located anywhere else in the genome, even on a completely different chromosome from the target gene. After production, they diffuse through the nucleus and search for their specific binding sites on the cis-acting elements.
For example, a transcription factor protein (a trans factor) encoded on Chromosome 1 might bind to an enhancer sequence (a cis element) adjacent to a gene on Chromosome 11. When the trans factor binds to the cis element, it can activate or repress the transcription of the nearby gene. This regulatory system allows a single trans factor to coordinate the expression of multiple genes across the genome, provided those genes share the same recognizable cis element.
Allele Positioning on Homologous Chromosomes
The cis and trans terminology is also used in classical genetics to describe the arrangement of linked alleles on homologous chromosomes, a concept separate from molecular gene regulation. Linked genes are located close together on the same chromosome, meaning they tend to be inherited together. In a diploid organism heterozygous for two linked genes (e.g., Gene A and Gene B), the physical arrangement of the alleles determines the configuration.
When the two dominant alleles (A and B) are found on one homologous chromosome and the two recessive alleles (a and b) are on the other, the arrangement is known as the Cis configuration (or coupling phase). This is represented as A B / a b, where the slash separates the two homologous chromosomes. This arrangement means the dominant traits are coupled on one chromosome and the recessive traits are coupled on the other.
The alternative arrangement is the Trans configuration, also called the repulsion phase. In this case, one dominant allele and one recessive allele are found on each homologous chromosome, such as A b / a B. This configuration dictates the relative frequency of parental versus recombinant offspring produced during genetic crosses, as recombination events happen less often between closely linked genes.