Howard Hughes Medical Institute

2011 Holiday Lectures on Science

Regulation of the Lactase Gene

About This Worksheet

This worksheet complements the Click and Learn “Regulation of the Lactase Gene” developed in
conjunction with the 2011 HHMI Holiday Lectures on Science “Bones, Stones, and Genes: The Origin
of Modern Humans.”
Author: Ann Brokaw, Rocky River High School, OH.

Key Concepts
• Eukaryotic gene expression is regulated at the levels of transcription, RNA processing, translation, and post-translation.
• Proteins called transcription factors bind to DNA and control transcription. Different types of transcription factors can
increase or decrease transcription.
• Mutations in DNA regions that control gene expression can alter the way genes are expressed.
• Infants have high lactase levels so that they can digest their mothers’ milk, but lactase gene expression is turned off after
weaning.
• Lactase persistence is the trait that allows adults to continue to digest milk. It results from a mutation in an enhancer region
of the lactase gene.
Instructions
1. Go to BioInteractive.org.
2. In the menu bar under the masthead, mouse over Topics →Evolution→Interactive.
3. Scroll down the page and click on “Regulation of the Lactase Gene.”
4. Proceed through the slides, watch the embedded video clips, and answer the following questions in the space
provided.
Questions
1. What is the difference between lactose tolerance and lactose intolerance? Be specific.
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Lacotse tolerance is being able to digest Lactose into Glucose + Galactose with an enzyme called Lactase. Lactose intolerance is not being able to digest Lactose because your body cannot

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produce Lactase.

2. Why is lactose tolerance also called lactase persistence?

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Because it's the trait that allows adults to continue digesting milk after infancy.

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3. In which cells or tissues is lactase produced and what is its role?

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Lactase is expressed in the cells of the small intestine.

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4. What normally happens to the levels of lactase produced throughout a person’s lifetime?
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After weaning, humans normally stop producing Lactase and become lactose intolerant
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5. In general, why is it important for a cell to regulate protein production?

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The system needs to have enough protein to function, but not to the point where it wastes energy

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 6. What are the steps in gene expression that ultimately affect protein levels in a eukaryotic cell?
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Transcription, RNA splicing, and Translation.

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7. What is the role of general transcription factors and where do they bind?
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General transcription factors bind to promoters, They facilitate the binding of RNA polymerase to the start position of a gene.

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8. How do activators and repressors affect transcription?

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If there is 2 activators and no repressors, transcription occurs. If there is only 1 activator present and no repressors- little to no transcription occurs. If a repressor is present no

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transciption.

9. Where do activators bind?

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Some activators bind to the regulatory region of DNA near the promoter region, others bind to a distant region of the chromosome called the enhancer region

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10. What are two ways in which repressors can interfere with transcription?

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They inhibit the activation of transcription. Some bind to the activator region, and prevent activators from binding to DNA, and others intefere with the molecular interactions betweeen

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activators and RNA polyamerase.

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11. Multicellular organisms are made up of different types of differentiated cells. Given that all cells in an organism
have the same DNA—and thus the same genes—explain how it is that different genes can be expressed only in
certain types of cells.
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Different patterns of expression can cause various cells to have different proteins, making it so certain cells have unique jobs.

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12. Is RNA processing a common way for regulating gene expression?

no
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13. What is alternative splicing and why is it important?

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Splicing different exons together. This is important for enriching the pattern of gene expression in eukaryotes

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14. What is translation?

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The process that produces proteins by decoding the sequence of mRNA codons.

15. RNA interference is a major mechanism of gene regulation in eukaryotes. Explain how RNA interference works.
In the case of the exciting new field of RNA interference, small pieces of RNA bind to m R N A to trigger degradation or
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block translation, thus shutting down gene expression.
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16. Which proteins are marked for destruction?

If active proteins either are no longer needed or are damaged, they are marked for destruction.
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 17. How does a cell know which proteins should be destroyed?
Proteasomes recognize and degrade proteins that have been tagged with the molecule ubiquitin.
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18. How are these proteins destroyed?

Degradation of proteins occurs through large protein complexes called proteasomes.
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19. At what level (i.e., transcription, translation, or protein processing) is the lactase gene (LCT) regulated?
 LCT gene transcription is drastically reduced, resulting in very low levels of lactase
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20. Using your knowledge of activators and repressors, hypothesize two ways in which transcription of the LCT gene
could be turned off.
1. Repressor binds to the activator's site and block transcription
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2. Repressor interact with the polymerase and block transcription
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21. In what regions of the world is lactase persistence most prevalent?

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Northern Europe and regions in Africa

22. How is lactase persistence an example of human evolution?

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Called lactase persistence, this is thought to be a human evolutionary adaptation to drinking milk from domesticated
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animals. The mutation appeared at about the same time as the domestication of cattle, according to archaeological
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evidence.

23. Explain the effect of the mutation that occurs among northern European people on LCT gene expression.
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They can digest dairy completely while many other parts of the world cannot.
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24. What are the similarities and differences between the lactase persistence mutations found in African
populations and the one found in European populations? (Consider, for example, type of mutation, location,
function.)
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The mutation that arose in northern Europe strengthens the binding of a transcription factor called Oct-1 to the enhancer
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region. The mutation that arose in Africa appears to use a different mechanism.
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About the Holiday Lectures on Science and BioInteractive.org

As part of its mission to strengthen science education, HHMI presents the Holiday Lectures on Science, an annual series that brings the latest developments in a rapidly moving field of research into the classroom. The
lectures are given by HHMI investigators and other leading scientists. The 2011 Holiday Lectures, Bones, Stones, and Genes: The Origin of Modern Humans, were the 19th in the series, which began in 1993.
To complement the Holiday Lectures and enhance their usefulness in the classroom, HHMI produces a variety of free science education materials. Lecture summaries, biographies of the lecturers, and other resources are
available at www.holidaylectures.org. DVDs and CD-ROMs can be ordered through HHMI’s Catalog at http://catalog.hhmi.org.
The BioInteractive website (www.BioInteractive.org) features virtual labs, animations, and other engaging instructional materials. They can be used to supplement the lecture topics or to learn important concepts in the
biomedical sciences.

About the Howard Hughes Medical Institute

The Howard Hughes Medical Institute is a nonprofit medical research organization that employs hundreds of leading
biomedical scientists working at the forefront of their fields. In addition, through its grants program and other
activities, HHMI is helping enhance science education at all levels and maintain the vigor of biomedical science
worldwide. Headquartered in Chevy Chase, Maryland, HHMI is one of the world's largest philanthropies, with
Department of Science Education laboratories across the United States and grants programs throughout the world.

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