Intro to gene expression (central dogma) (article) | Khan Academy
The over-retention of some functional categories suggests that WGDs To investigate in detail the relation between gene expression and gene .. for expression of a gene, given the cellular resources that can be used for its. The process of gene expression involves two main stages: An enzyme peptidyl transferase links the amino acids together using peptide bonds. metabolic functions; some genes are expressed as part of the process of cell differentiation; . ACTIVITY OVERVIEW. Students investigate gene expression as it relates to cell stored in DNA is used to produce a functional gene product. Gene products are the enzyme that links ribonucleotides together to form RNA. Transcription is.
The horizontal dashed line represents the average retention rate following the recent WGD. The solid lines correspond to locally-weighted polynomial regression lowess, as implemented in the R software . Relationship between gene expression and gene retention across different functional categories.
Functional categories were taken from the Gene Ontology classification  as indicated in each panel. For each category, ohnologons were grouped into four quartiles of expression level and the average retention rate was computed as the frequency of ohnologons having retained both copies since the recent WGD.
The dotted line corresponds to the average retention rate of all genes with a GO classification.
Relationship between non-synonymous substitution rates and expression level. Values of non-synonymous divergence Ka between ohnologs from the recent WGD were taken from .
The solid red line shows the linear regression between Ka and expression level. Detailed analysis of functional categories.
For each functional category, the indications given by the table are: GO number of the functional category. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated.
Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression.
This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.
Author Summary The analysis of gene evolution is a powerful approach to recognize the genetic features that contribute to the fitness of organisms. It was shown previously that selective constraints on protein sequences increase with expression level.
This observation was surprising because there is a priori no reason why lowly expressed genes should be less important than highly expressed genes for the proper function of an organism.
Here we show that selective pressure on the evolution of gene dosage, which is another important aspect of gene evolution, is also directly dependent on gene expression level. To explain these observations, we propose a model based on the fact that gene expression is a costly process notably protein synthesisso that there is an optimal expression level for each gene corresponding to a trade-off between the benefit and the cost of its expression.
This model predicts that selective pressure on gene expression level or on the encoded protein should on average be stronger in highly expressed genes, providing a simple and common explanation for the general relationship observed between gene expression and the different facets of gene evolution. Introduction Mutations can affect the phenotype either by modifying the sequences of proteins or by changing their pattern of expression.
Whereas the evolutionary constraints acting on protein-coding sequences are relatively well characterized, those driving the evolution of gene expression have been much less studied.
Intro to gene expression (central dogma)
Modifications in gene expression can result from mutations in regulatory elements or through changes in the number of gene copies in the genome i. The phenotypic impact of changes in gene dosage is clearly illustrated by the deleterious effects caused by chromosome aneuploidy .
The necessity of an X-chromosome inactivation mechanism to compensate for dosage imbalance between males and females in mammals  is another example of the importance of having the correct dosage of genes. Within populations, polymorphism in copy number of genes Copy Number Variations: CNVs significantly contributes to variations in transcript abundance .
Moreover, some CNVs were shown to be driven by positive selection for increased expression of the corresponding genes  — highlighting the fact that gene dosage modifications can be targeted by selection. However, the evolutionary constraints that apply on gene dosage remain poorly understood.
Whole-genome duplications WGDs represent interesting cases to study the evolutionary constraints on gene dosage.
Immediately after a WGD event, all genes are present in two copies; these paralogs that result from WGD are termed ohnologs, in reference to the pioneering ideas of Susumu Ohno on the role of WGDs in genome evolution .
However progressive changes in gene dosage do occur: Regulation of gene expression refers to the control of the amount and timing of appearance of the functional product of a gene.
Control of expression is vital to allow a cell to produce the gene products it needs when it needs them; in turn, this gives cells the flexibility to adapt to a variable environment, external signals, damage to the cell, and other stimuli. More generally, gene regulation gives the cell control over all structure and function, and is the basis for cellular differentiationmorphogenesis and the versatility and adaptability of any organism.
Numerous terms are used to describe types of genes depending on how they are regulated; these include: A constitutive gene is a gene that is transcribed continually as opposed to a facultative gene, which is only transcribed when needed.
A housekeeping gene is a gene that is required to maintain basic cellular function and so is typically expressed in all cell types of an organism. Some housekeeping genes are transcribed at a relatively constant rate and these genes can be used as a reference point in experiments to measure the expression rates of other genes. A facultative gene is a gene only transcribed when needed as opposed to a constitutive gene. An inducible gene is a gene whose expression is either responsive to environmental change or dependent on the position in the cell cycle.
Any step of gene expression may be modulated, from the DNA-RNA transcription step to post-translational modification of a protein. The stability of the final gene product, whether it is RNA or protein, also contributes to the expression level of the gene—an unstable product results in a low expression level. In general gene expression is regulated through changes  in the number and type of interactions between molecules  that collectively influence transcription of DNA  and translation of RNA.
Control of insulin expression so it gives a signal for blood glucose regulation. X chromosome inactivation in female mammals to prevent an "overdose" of the genes it contains. Cyclin expression levels control progression through the eukaryotic cell cycle.
Transcriptional regulation When lactose is present in a prokaryote, it acts as an inducer and inactivates the repressor so that the genes for lactose metabolism can be transcribed. Regulation of transcription can be broken down into three main routes of influence; genetic direct interaction of a control factor with the genemodulation interaction of a control factor with the transcription machinery and epigenetic non-sequence changes in DNA structure that influence transcription.
The lambda repressor transcription factor green binds as a dimer to major groove of DNA target red and blue and disables initiation of transcription. Direct interaction with DNA is the simplest and the most direct method by which a protein changes transcription levels.
Genes often have several protein binding sites around the coding region with the specific function of regulating transcription. There are many classes of regulatory DNA binding sites known as enhancersinsulators and silencers. The mechanisms for regulating transcription are very varied, from blocking key binding sites on the DNA for RNA polymerase to acting as an activator and promoting transcription by assisting RNA polymerase binding.
The activity of transcription factors is further modulated by intracellular signals causing protein post-translational modification including phosphorylatedacetylatedor glycosylated.
These changes influence a transcription factor's ability to bind, directly or indirectly, to promoter DNA, to recruit RNA polymerase, or to favor elongation of a newly synthesized RNA molecule. The nuclear membrane in eukaryotes allows further regulation of transcription factors by the duration of their presence in the nucleus, which is regulated by reversible changes in their structure and by binding of other proteins.
More recently it has become apparent that there is a significant influence of non-DNA-sequence specific effects on transcription. In general epigenetic effects alter the accessibility of DNA to proteins and so modulate transcription.
In eukaryotes, DNA is organized in form of nucleosomes. Note how the DNA blue and green is tightly wrapped around the protein core made of histone octamer ribbon coilsrestricting access to the DNA.
DNA methylation is a widespread mechanism for epigenetic influence on gene expression and is seen in bacteria and eukaryotes and has roles in heritable transcription silencing and transcription regulation. In eukaryotes the structure of chromatincontrolled by the histone coderegulates access to DNA with significant impacts on the expression of genes in euchromatin and heterochromatin areas.
Transcriptional regulation in cancer[ edit ] Main article: Regulation of transcription in cancer The majority of gene promoters contain a CpG island with numerous CpG sites. For example, in colorectal cancers about to genes are transcriptionally silenced by CpG island methylation see regulation of transcription in cancer.
Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered expression of microRNAs. Post-transcriptional regulation In eukaryotes, where export of RNA is required before translation is possible, nuclear export is thought to provide additional control over gene expression.
All transport in and out of the nucleus is via the nuclear pore and transport is controlled by a wide range of importin and exportin proteins.
Expression of a gene coding for a protein is only possible if the messenger RNA carrying the code survives long enough to be translated. In a typical cell, an RNA molecule is only stable if specifically protected from degradation. RNA degradation has particular importance in regulation of expression in eukaryotic cells where mRNA has to travel significant distances before being translated.
In eukaryotes, RNA is stabilised by certain post-transcriptional modifications, particularly the 5' cap and poly-adenylated tail. Three prime untranslated regions and microRNAs[ edit ] Main article: By binding to specific sites within the 3'-UTR, miRNAs can decrease gene expression of various mRNAs by either inhibiting translation or directly causing degradation of the transcript.
These are prevalent motifs within 3'-UTRs. Among all regulatory motifs within the 3'-UTRs e. As ofthe miRBase web site,  an archive of miRNA sequences and annotations, listed 28, entries in biologic species. Translation genetics Direct regulation of translation is less prevalent than control of transcription or mRNA stability but is occasionally used.
Inhibition of protein translation is a major target for toxins and antibioticsso they can kill a cell by overriding its normal gene expression control.
Studying Gene Expression and Function - Molecular Biology of the Cell - NCBI Bookshelf
Protein synthesis inhibitors include the antibiotic neomycin and the toxin ricin. Proteasome Once protein synthesis is complete, the level of expression of that protein can be reduced by protein degradation. There are major protein degradation pathways in all prokaryotes and eukaryotes, of which the proteasome is a common component. An unneeded or damaged protein is often labeled for degradation by addition of ubiquitin. Measurement[ edit ] Measuring gene expression is an important part of many life sciencesas the ability to quantify the level at which a particular gene is expressed within a cell, tissue or organism can provide a lot of valuable information.
For example, measuring gene expression can: Identify viral infection of a cell viral protein expression. Determine an individual's susceptibility to cancer oncogene expression. Find if a bacterium is resistant to penicillin beta-lactamase expression. Similarly, the analysis of the location of protein expression is a powerful tool, and this can be done on an organismal or cellular scale.
Investigation of localization is particularly important for the study of development in multicellular organisms and as an indicator of protein function in single cells. Ideally, measurement of expression is done by detecting the final gene product for many genes, this is the protein ; however, it is often easier to detect one of the precursors, typically mRNA and to infer gene-expression levels from these measurements. A sample of RNA is separated on an agarose gel and hybridized to a radioactively labeled RNA probe that is complementary to the target sequence.
The radiolabeled RNA is then detected by an autoradiograph. Because the use of radioactive reagents makes the procedure time consuming and potentially dangerous, alternative labeling and detection methods, such as digoxigenin and biotin chemistries, have been developed. Perceived disadvantages of Northern blotting are that large quantities of RNA are required and that quantification may not be completely accurate, as it involves measuring band strength in an image of a gel.
On the other hand, the additional mRNA size information from the Northern blot allows the discrimination of alternately spliced transcripts. In this technique, reverse transcription is followed by quantitative PCR.
The cDNA template is then amplified in the quantitative step, during which the fluorescence emitted by labeled hybridization probes or intercalating dyes changes as the DNA amplification process progresses. With a carefully constructed standard curve, qPCR can produce an absolute measurement of the number of copies of original mRNA, typically in units of copies per nanolitre of homogenized tissue or copies per cell.
For expression profilingor high-throughput analysis of many genes within a sample, quantitative PCR may be performed for hundreds of genes simultaneously in the case of low-density arrays.