Omar Bennett
Gene expression is the process by which cells read out or express the genetic instructions in their genes. The control of expression is vital to allow a cell to produce the gene products it needs when it needs them. Constitutive genes are those that are continuously and constantly expressed, and are unregulated, meaning their expression level is relatively constant. In contrast, facultative genes are only transcribed when needed. A mutation that prevented the lac repressor from binding to the operator would make the lac operon constitutive only in the absence of glucose. However, this mutation would not be entirely constitutive because transcription would be inhibited in the presence of glucose.
| Characteristics | Values |
|---|---|
| Definition | Constitutive genes are those genes that are continuously and constantly expressed. |
| Regulation | Constitutive genes are unregulated, meaning their expression level is relatively constant. |
| Comparison with Regulated Genes | The expression of regulated genes varies under different conditions. |
| Transcription | Constitutive genes are transcribed continually. |
| Examples | Actin, GAPDH, and ubiquitin. |
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What You'll Learn
A gene encoding a stress hormone
For example, the SERPINA6/A1 gene is a genetic variant that helps control human cortisol levels, which is a stress hormone. This gene controls cortisol levels in the blood, particularly in the morning. Cortisol levels vary throughout the day, and high levels of it are associated with illnesses such as heart disease, type 2 diabetes, and depression. Therefore, the SERPINA6/A1 gene would need to be regulated to control the amount of cortisol in the body.
The GR gene has also been found to be involved in the genetics of the stress response, as it is a major regulator of stress hormone activity at the pituitary level. The limbic-hypothalamic-pituitary-adrenal axis (LHPA) is the primary circuit that initiates, regulates, and terminates a stress response. This shows that genes encoding stress hormones are regulated to manage the body's response to stress.
Additionally, the renin-angiotensin-aldosterone system, which is involved in water regulation and blood volume and pressure, has been associated with stress responses and cardiovascular disorders. This further indicates that genes related to stress hormones need to be regulated to maintain homeostasis in the body.
In summary, a gene encoding a stress hormone is not likely to be constitutively expressed because it needs to be regulated to vary its expression depending on the body's needs and external conditions.
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The lac operon
Mutations may affect the expression of the lac operon. For example, a mutation in the operator site that prevents the lac repressor from binding to it would make the lac operon constitutive only in the absence of glucose. However, this mutation would not be entirely constitutive because transcription would be inhibited in the presence of glucose. The disadvantage of constitutive expression of the lac operon is that the bacterial cell would waste energy transcribing the genes and translating the mRNA when lactose is not present.
The complete regulation of the lac operon is quite complex, and it was the first genetic regulatory mechanism to be clearly understood. It has become a foremost example of prokaryotic gene regulation and is often discussed in introductory molecular and cellular biology classes. The work on the lac operon won François Jacob and Jacques Monod the Nobel Prize in Physiology in 1965.
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The trp operon
The trpR repressor significantly reduces transcription, and attenuation further decreases it, resulting in an overall accumulated repression of about 700-fold. The repressor system targets intracellular trp concentration, while attenuation responds to the concentration of charged tRNAtrp. Thus, the trpR protein reduces gene expression by altering the initiation of transcription, while attenuation alters the efficiency of transcription termination.
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Housekeeping genes
The concept of "housekeeping genes" has been used for four decades but remains loosely defined. They are commonly described as "essential for cellular existence, regardless of their specific function in the tissue or organism", and stably expressed irrespective of tissue type, developmental stage, cell cycle state, or external signal. Housekeeping genes account for the majority of the active genes in the genome, and their expression is vital to survival. The expression levels of housekeeping genes are fine-tuned to meet the metabolic requirements of various tissues.
Examples of housekeeping genes include actin, GAPDH, and ubiquitin. Some of these genes are transcribed at a relatively constant rate, while the expression of others may vary depending on experimental conditions. The experimental support for the link between gene essentiality and stable expression across cell types, conditions, and organisms has been limited. However, recent studies using genome-scale functional genomic screens and sequencing technologies aim to optimize a quantitative and experimentally validated definition of housekeeping genes.
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DNA methylation
Methylation occurs on cytosines in dinucleotide sequences, where a cytosine is followed by a guanine, known as a CpG site. In mammals, DNA methylation is predominantly found in CpG dinucleotides, with methylation occurring on cytosines on both strands. The number of CpG sites in the human genome is approximately 28 million, and about 70% of these sites have a methylated cytosine. Methylation of CpGs in a promoter region of a gene typically represses gene transcription, while methylation of CpGs within the body of a gene increases expression.
The process of DNA methylation is catalyzed by a family of enzymes called DNA methyltransferases (Dnmt). These enzymes transfer a methyl group from S-adenyl methionine (SAM) to the fifth carbon of a cytosine residue, forming 5-methylcytosine (5mC). Dnmt1, a specific type of Dnmt, plays a crucial role during DNA replication by copying the DNA methylation pattern from the parental DNA strand to the newly synthesized daughter strand.
While DNA methylation is a stable process in postmitotic cells, neuronal activity can influence the methylation pattern in response to physiological and environmental stimuli. The brain exhibits some of the highest levels of DNA methylation among body tissues, yet 5mC only accounts for about 1% of nucleic acids in the human genome. This highlights the dynamic nature of DNA methylation and its potential for therapeutic interventions in neuropsychiatric disorders.
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