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How is gene expression controlled, and how do genes such as the lac operon and homeobox genes regulate cells and development?

6.1.1 Cellular control: the nature of gene mutations and their effects on proteins; the control of gene expression at the transcriptional level, including operons (the lac operon) and transcription factors; the role of homeobox (Hox) genes in body plan development; and the role of apoptosis (programmed cell death).

A focused answer to the OCR H420 6.1.1 dot point on cellular control. Covers gene mutations and their effects, the control of transcription by the lac operon and transcription factors, the role of homeobox (Hox) genes in body plan development, and apoptosis.

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What this dot point is asking

OCR wants you to describe gene mutations and their effects on proteins, explain the control of gene expression at transcription including the lac operon and transcription factors, explain the role of homeobox (Hox) genes in body plan development, and explain the role of apoptosis.

The answer

Gene mutations

A gene mutation is a change in the base sequence of DNA:

  • Substitution: one base replaced by another, changing one codon. Because the code is degenerate, it may be silent (same amino acid), or change one amino acid (missense), or create a stop codon (nonsense).
  • Insertion or deletion: adding or removing a base causes a frameshift, changing every codon after the mutation, so the protein is usually completely altered and non-functional.

A changed amino acid may alter the protein's tertiary structure (and so its function, for example at an active site). Many mutations occur in non-coding DNA or are silent and have no effect.

Control of transcription: the lac operon

In prokaryotes, genes are controlled in operons: a cluster of structural genes with shared control regions. The lac operon controls lactose metabolism in E. coli:

  • Without lactose: a regulatory gene makes a repressor protein that binds the operator, blocking RNA polymerase from the promoter, so the structural genes are not transcribed.
  • With lactose: lactose (as allolactose) binds the repressor, changing its shape so it detaches from the operator; RNA polymerase can now transcribe the structural genes, and the lactose-metabolising enzymes are made.

This is efficient: the enzymes are made only when their substrate is present.

Transcription factors

In eukaryotes, transcription factors are proteins that bind to DNA (at promoters and enhancers) to switch transcription on or off by helping or preventing RNA polymerase binding. Hormones can act through them: for example, a steroid hormone enters a cell and binds a receptor that acts as a transcription factor, switching specific genes on. Gene expression can also be controlled by epigenetic changes such as DNA methylation (silencing genes) and histone modification.

Homeobox (Hox) genes

Homeobox genes contain a conserved homeobox sequence coding for a homeodomain that binds DNA, so the proteins act as transcription factors controlling other genes. Hox genes are a group of homeobox genes that control the body plan during development, switching on the genes that determine which structures form where along the body axis (for example where limbs develop). They are highly conserved across very different animals, evidence of common ancestry.

Apoptosis

Apoptosis is programmed cell death: the cell breaks down in a controlled way (the cytoskeleton breaks, the membrane blebs, the DNA fragments, and the cell breaks into vesicles that are engulfed by phagocytes), without releasing harmful contents. It is essential in development (for example removing the webbing between fingers) and in removing damaged or infected cells. Too little apoptosis can lead to cancer; too much can cause degenerative disease.

Examples in context

Example 1. Sickle-cell anaemia. A single substitution in the gene for the beta-globin chain of haemoglobin changes one amino acid (glutamate to valine), altering the protein's structure so it distorts red blood cells, a clear case of a missense mutation affecting protein function.

Example 2. Hox genes and limb position. Mutations in Hox genes can cause structures to form in the wrong place (for example legs where antennae should be in fruit flies), showing how these master regulator genes control the body plan.

Try this

Q1. Explain why a substitution mutation may have no effect on the protein produced. [2 marks]

  • Cue. The genetic code is degenerate, so the new codon may still code for the same amino acid (a silent mutation), leaving the protein unchanged.

Q2. Describe the role of the repressor protein in the lac operon when lactose is absent. [2 marks]

  • Cue. It binds to the operator, preventing RNA polymerase from binding the promoter, so the structural genes are not transcribed and the enzymes are not made.

Q3. State what is meant by apoptosis. [1 mark]

  • Cue. Programmed (controlled) cell death.

Exam-style practice questions

Practice questions written in the style of OCR exam questions on this dot point, with worked answer explainers. The year tag is the paper they imitate, not the source.

OCR H420/02 20196 marksDescribe how the lac operon controls the production of the enzymes needed to metabolise lactose in a bacterium.
Show worked answer →

Contrast the operon with and without lactose.

Without lactose: the regulatory gene produces a repressor protein that binds to the operator region. This blocks RNA polymerase from binding to the promoter, so the structural genes (for example for lactose-metabolising enzymes) are not transcribed: the enzymes are not made when they are not needed.

With lactose: lactose (as allolactose) binds to the repressor, changing its shape so it can no longer bind the operator. RNA polymerase can now bind the promoter and transcribe the structural genes, so the enzymes are made and lactose is metabolised.

Markers reward the repressor binding the operator to block transcription without lactose, and lactose binding the repressor (changing its shape) so transcription proceeds when lactose is present.

OCR H420/02 20214 marksExplain how a substitution mutation in a gene may or may not change the protein produced.
Show worked answer →

Use the degenerate code and the position of the change.

A substitution changes one base for another, altering one codon. Because the genetic code is degenerate (several codons code for the same amino acid), the new codon may still code for the same amino acid, so the protein is unchanged (a silent mutation).

If the new codon codes for a different amino acid, the primary structure changes; this may alter the folding and the tertiary structure, potentially changing or destroying the protein's function (for example if it is at an active site). A substitution that creates a stop codon would truncate the protein.

Markers reward the degenerate code allowing a silent mutation, and a changed amino acid potentially altering the tertiary structure and function.

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