Bio Review Notes #36
GENE CONTROL IN DEVELOPMENT
Performance Objectives:
In general, genes control development by making proteins, including enzymes, that control other processes. These proteins need to differ by cell type, sex, developmental age, or physiological condition.
The operon theory provides one model to explain gene regulation in procaryotes.

Gene control: Genes control cell processes by making enzymes and other proteins. However, these proteins need to vary from one cell type to another.
Example: All human cells have genes for insulin, but only one type of pancreas cell makes insulin, and only when it is needed.
  • Different proteins are needed in embryos, children, and adults.
  • Many genes or gene products (for beard development, antlers, or milk production) are needed in one sex but not the other.
  • Gene products are also needed in differing amounts. When certain substrates are present, more enzymes are needed to break them down, but it is wasteful to produce more than is needed.
  • All genes were once thought to make enzymes ("one gene, one enzyme"). Now we know that some gene products regulate other genes.

Types of gene control:
  • Positive control: genes normally "off"; turned "on" when needed
  • Negative control: genes normally "on"; can be turned "off"
  • Constitutive (no control): gene is always "on"
  • Transcriptional control: regulates whether or not a gene is transcribed
  • Translational control: regulates whether or not a mRNA is translated into protein

Gene control in procaryotes:
Procaryotic genes are often regulated as parts of operons, meaning groups of genes regulated together as a unit ("coordinated regulation"; all turned on or all turned off at the same time). The genes in an operon are usually related in function, as by making enzymes that control successive steps in a biochemical pathway. All known operons are transcriptionally regulated.
  • The lac operon of E. coli is the best-known operon. It contains, in order, a repressor gene (lacI), a promoter (lacP), an operator (lacO), and three structural genes (lacZ, lacY, lacA), that make enzymes concerned with lactose metabolism.
  • Transcription requires that RNA polymerase first bind to the promoter region. The lac mRNA that results contains all 3 structural genes.
  • The repressor gene makes a repressor protein that binds to the operator, preventing transcription, a form of negative control. Transcription stops before reaching the structural genes.
  • When gene producs are needed, an inducer protein (made elsewhere) combines with the repressor and inactivates it. This process, derepression, exposes the operator, allowing transcription to proceed.
  • Transcription of lac mRNA also requires cyclic AMP and catabolite activator protein, a form of positive control.
  • Some operons are autoregulated: the gene product acts as its own repressor. A small amount of product, always present, represses the needless synthesis of any more product. If this small amount is used up, the gene is derepressed and more product is made.

Gene control in eucaryotes: Gene control is more complex and less well understood in eucaryotes.
  • Most mRNA in eucaryotes contains only one gene at a time.
  • Much eucaryotic DNA is never translated, but consists of repeated sequences, which occur hundreds to several millions of times.
  • Most eucaryotic DNA is bound to histone proteins, forming chromatin. DNA cannot be transcribed when the histones remain tightly bound; this may be the key to one method of gene regulation.
  • Oocytes need genes for ribosomal RNA very numerously to make the RNA needed to make yolk proteins. Gene amplification greatly increases (temporarily) the number of copies of these genes.
  • Many eucaryotic genes belong to gene families, believed to have originated from the duplication of one original gene and the subsequent mutation of the resultant copies.
  • Many eucaryotic genes consist of discontiguous fragments that must be spliced together after transcription but before translation. In some cases, such as the gene for the muscle protein tropomyosin, the same gene sequence can be spliced together in several different ways, resulting in distinct gene products in different cell types.
  • Genes that produce antibodies have a special mechanism that pieces together several gene fragments, allowing a few hundred fragments rapidly to generate many millions of new variants.


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