Regulation of Gene Expression

According to the Human Genome Project, the total number of protein-coding genes is about 20,000 with about 13 genes encoded in the mitochondrial genome. Only about 12 percent of the entire genome consists of protein-coding genes, with the rest being introns, noncoding RNAs, and things called retrotransposons.

Essential genes are believed to be critical for the survival of the organism. This number is small in bacteria and represents only about 250-400 genes—less than 10 percent of existing genes. Most are involved in protein synthesis. Humans are believed to have 2000 essential genes. A synthetic organism has been created that has a minimal genome, consisting of about 473 essential genes in the organism. Essential genes are used for basic cell functions and for the life cycle of the organism.

Most proteins come from transcribed messenger RNA. Some genes are called RNA genes because the genes’ end products are the actual RNA molecules. These include transfer RNA and ribosomal RNA. Some RNA molecules are referred to as ribozymes, which are actually capable of enzymatic functionality, while microRNA is made to serve as regulatory molecules. The genes that make these products are called non-coding RNA genes.

REGULATION OF GENE EXPRESSION

Gene regulation is the process of controlling which genes get expressed at different times. Not all genes can be expressed in the different cells of the organism, even though all cells have the same copy of DNA. The different set of genes that get expressed determines what properties the cell has. There are many different regulatory steps in gene regulation—most of them affiliated with the transcription of genes.

The cell will regulate its gene expression depending on what it perceives are the external environmental factors. These include the temperature, environmental stresses, and available nutrients. Internal signals, such as whether or not the cell is infected and metabolic needs, will also determine gene expression. Gene expression can happen in transcription (most common), in RNA processing, in translation, and in posttranslational modification.

Gene regulation determines what the cell does and what it looks like. Cells that need a certain protein or enzyme will have the gene for that enzyme turned on at some point. Cells that will never need a protein turned on will have that segment of DNA blocked from transcribing. There can be growth factors that bind to cell receptors after being created because of internal factors or because a receptor turns on their production. The growth factor triggers a set of transcription factors to get made that will activate a promotor region in the DNA molecule so that the gene gets turned on.

In reality, genes can be regulated at multiple levels so that the numbers and quality of proteins made by the cell can change according to need. As mentioned, transcription is the most common way that genes get regulated. The different ways that genes can be regulated include the following:

• Chromatin accessibility—the chromatin can be tightly wound or can be more relaxed in order to make the genes more available for transcription.

• Transcription—the most common regulatory mechanism, in which transcriptional factors bind to DNA sequences that will promote or repress the

DNA’s transcription. • RNA processing—this is the processing that happens to RNA causing it to be allowed or not allowed to leave the nucleus for translation. The same pre-mRNA can result in a different messenger RNA molecule, depending on how it’s spliced. • mRNA stability—messenger RNA can be broken down quickly or stay stable for long periods of time, depending on factors inside the cytosol. MicroRNA can bind to mRNA, causing it to be chopped up rather than used.

• Translation—there may be more or less of the ability to translate into a polypeptide.

• Protein processing—there can be changes in post-translational modification so that the protein can be used (or not used) in a specific way.

Interestingly, DNA can be regulated between species. While humans share 98.8 percent of DNA within chimpanzees, there are great differences in phenotype. Besides these similarities and differences, genes that are identical between primates and humans can

cause species’ differences because they regulate the numbers and types of genes that get expressed between the different species.