Each somatic cell in the body generally contains the same DNA. A few exceptions include red blood cells, which contain no DNA in their mature state, and some immune system cells, which rearrange their DNA while producing antibodies. In general, however, the genes that determine whether you have green eyes, brown hair, or how fast you metabolize food are the same in the cells in your eyes and your liver, even though these organs function quite differently. If each cell has the same DNA, how is it that cells or organs are different? Why do cells in the eye differ so dramatically from cells in the liver?
Whereas each cell shares the same genome and DNA sequence, each cell does not turn on, or express, the same set of genes. Each cell type needs a different set of proteins to perform its function. Therefore, only a small subset of proteins is expressed in a particular cell. For the proteins to be expressed, the DNA must be transcribed into RNA and the RNA must be translated into protein. In a given cell type, not all genes encoded in the DNA are transcribed into RNA and translated into protein because specific cells in our body have specific functions. Specialized proteins that make up the eye (iris, lens, and cornea) are only expressed in the eye, whereas the specialized proteins in the heart (pacemaker cells, heart muscle, and valves) are only expressed in the heart. At any given time, only a subset of all of the genes encoded by our DNA are expressed and translated into proteins. The expression of specific genes is a highly regulated process with many levels and stages of control. This complexity ensures the proper expression in the proper cell at the proper time.
Regulation of gene expression
For a cell to function properly, necessary proteins must be synthesized at the proper time and place. All cells control or regulate the synthesis of proteins from information encoded in their DNA. The process of turning on a gene to produce RNA and a protein is called gene expression. Whether in a simple unicellular or a complex multicellular organism, each cell controls when and how its genes are expressed. For this to occur, there must be internal chemical mechanisms that control when a gene is expressed to make RNA and protein, how much of the protein is made, and when it is time to stop making that protein because it is no longer needed.
Most of the activity of regulating gene expression is done in order to conserve cellular resources, especially space and energy. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required. In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly coiled structure to transcribe and translate the DNA. Cells would have to be enormous if every protein were expressed in every cell all the time.
Some regulatory processes may be defensive. Cellular processes such as developed to protect the cell from viral or parasitic infections. If the cell could quickly shut off gene expression for a short period of time, it would be able to survive an infection when other organisms could not. Therefore, the organism evolved a new process that helped it survive, and it was able to pass this new development to offspring.
The control of gene expression is extremely complex. Malfunctions in this process are detrimental to the cell and can lead to the development of many diseases, including cancer.
Prokaryotic versus eukaryotic gene expression
To understand how gene expression is regulated, we must first understand how a gene becomes a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different fashion (Figure 8.1).
Because prokaryotic organisms lack a cell nucleus and their DNA floats freely in the cell cytoplasm, to synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the protein is no longer needed, transcription stops. As a result, the primary method to control what type and how much protein is expressed in a prokaryotic cell is through the regulation of DNA transcription into RNA. All the subsequent steps happen automatically. When more protein is required, more transcription occurs. Therefore, in prokaryotic cells, the control of gene expression is almost entirely at the transcriptional level.
The first example of such control was discovered using Escherichia coli in the 1950s and 1960s by French researchers and is called lac operon. Lac operon is a stretch of DNA with three adjacent genes that code for proteins that participate in the absorption and metabolism of lactose, a food source for E. coli. When lactose is not present in the bacterium’s environment, the lac genes are transcribed in small amounts. When lactose is present, the genes are transcribed and the bacterium is able to use the lactose as a food source. The operon also contains a promoter sequence to which the RNA–polymerase binds to begin transcription; between the promoter and the three genes is a region called the operator. When there is no lactose present, a protein known as a repressor binds to the operator and prevents the RNA–polymerase from binding to the promoter, except in rare cases. Thus very little of the protein products of the three genes is made. When lactose is present, an end product of lactose metabolism binds to the repressor protein and prevents it from binding to the operator. This allows the RNA–polymerase to bind to the promoter and freely transcribe the three genes, allowing the organism to metabolize the lactose.
Eukaryotic cells, in contrast, have intracellular organelles and are much more complex. In eukaryotic cells, the DNA is contained inside the cell’s nucleus and transcribed into mRNA there. The newly synthesized mRNA is then transported out of the nucleus into the cytoplasm, where ribosomes translate the mRNA into protein. The processes of transcription and translation are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation only occurs outside the nucleus, in the cytoplasm.
Figure 8.1: Regulation in prokaryotes and eukaryotes. Prokaryotic transcription and translation occur simultaneously in the cytoplasm, and regulation occurs at the transcriptional level. Eukaryotic gene expression is regulated during transcription and RNA processing, which take place in the nucleus, and during protein translation, which takes place in the cytoplasm. Further regulation may occur through post-translational modifications of proteins.
| Prokaryotic organisms | Eukaryotic organisms |
|---|---|
| Lack a membrane-bound nucleus. | Contain nucleus. |
| DNA is found in the cytoplasm. | DNA is confined to the nucleus. |
| RNA transcription and protein formation occur almost simultaneously. | RNA transcription occurs prior to protein formation, and it takes place in the nucleus. Translation of RNA to protein occurs in the cytoplasm. |
| Gene expression is regulated primarily at the transcriptional level. | Gene expression is regulated at many levels (epigenetic, transcriptional, nuclear shuttling, post-transcriptional, translational, and post-translational). |
Table 8.1: Differences in the regulation of gene expression between prokaryotes and eukaryotes.
Eukaryotic gene expression
Eukaryotic gene expression is more complex than prokaryotic gene expression because the processes of transcription and translation are physically separated. Unlike prokaryotic cells, eukaryotic cells can regulate gene expression at all stages of the process (Figure 8.2). Thus, regulation may occur:
- when DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level);
- when RNA is transcribed (transcriptional level);
- when RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level);
- when RNA is translated into protein (translational level);
- after the protein has been made (post-translational level).
Figure 8.2: Eukaryotic gene expression is regulated during transcription and RNA processing, which take place in the nucleus, as well as during protein translation, which takes place in the cytoplasm. Further regulation may occur through post-translational modifications of proteins.