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Sequencing DNA
(high school science)
by Viki Babcock


After learning about the Human Genome Project, students perform a paper-cutting activity that simulates the action of restriction enzymes and helps them understand how DNA can be sequenced.

Estimated class time:

Two class periods -- one for viewing the video, and one for the activity.

Lesson Objectives:

Students will:
  • Identify key researchers in the Human Genome Project
  • Show, through simulation, how DNA can be sequenced using restriction enzymes
  • Evaluate the benefits of knowing the complete human genome.

Correlation to National Science Standards from

CONTENT STANDARD C: As a result of their activities in grades 9-12, all students should develop an understanding of the molecular basis of heredity:

  • In all organisms, the instructions for specifying the characteristics of the organism are carried in DNA, a large polymer formed from subunits of four kinds (A, G, C, and T). The chemical and structural properties of DNA explain how the genetic information that underlies heredity is both encoded in genes (as a string of molecular "letters") and replicated (by a templating mechanism). Each DNA molecule in a cell forms a single chromosome.
CONTENT STANDARD E: As a result of activities in grades 9-12, all students should develop understandings about science and technology:
  • Science often advances with the introduction of new technologies.

Materials needed:

  • TV/VCR
  • Copy of DNA EPISODE 3: "The Human Race"
  • Student handouts per group: Four copies of DNA 1, four copies of DNA 2, and two copies of Restriction Enzymes
  • Scissors
  • Tape

Teaching Strategy:

  • Review students' knowledge of the basic structure of DNA and their understanding of base-pairing.

  • View the video, DNA EPISODE 3: "THE HUMAN RACE." Direct students to take notes about the different scientists involved, the reasons behind pursuing the Human Genome Project, and the techniques involved in DNA sequencing.

  • Introduce (or review) the concepts of:

    1. polymerase chain reaction as a way to make multiple copies of a segment of DNA and
    2. restriction enzymes, which can be used to cut DNA into fragments of different lengths.

    Background information can be found at:

    DNA Soup: A Guide to PCR

    Restriction Enzymes Background Paper

    Restriction Enzymes

    What the Heck is PCR?

  • Divide the class into pairs. Provide one student of each pair with four copies of the DNA 1 student handout and one copy of the Restriction Enzyme student handout. Provide the other student of the pair with four copies of the DNA 2 handout and one copy of the Restriction Enzyme handout. Explain that the copies of "DNA" represent DNA that could have been duplicated via PCR techniques. Tell the students not to view their partner's DNA sample, because it will be their job to correctly sequence their partner's DNA once it has been cut into fragments using the restriction enzymes.

  • Instruct each student to cut apart the five strips of "DNA" on their handouts and to tape them together in order, forming a long strand of simulated DNA. Have students place the top of the next strip in the sequence over the lower end of the one before it covering that strip's number. Cut off the number "5" on the last strip as well, so that no visible clues to the proper order are left on the strips.

  • Each student should now choose any three of the restriction enzymes and cut out the appropriate cards from the handout. These show the particular DNA patterns that each enzyme will recognize. The line indicates where to cut the DNA. (This activity ignores the creation of sticky ends, so that sequencing the fragments will be more challenging.)

  • Starting at the top of one of their DNA strips, students look for the patterns recognized by their chosen enzymes by holding the enzyme card next to the DNA strip and moving it all the way down the length of the strip. Where the patterns match exactly, student should cut the DNA strip at the exact location (black line) indicated on the enzyme card. Students should be reminded that the pattern may occur more than once in their particular DNA sample. Repeat this procedure with the two other restriction enzymes cards and two more DNA strips. Leave one DNA strip intact. Be sure that students use only one enzyme card for each strip of DNA.

  • At this point, the partners shuffle and then trade the cut pieces of DNA with each other. Each student then manipulates the DNA fragments, looking for overlapping patterns and attempts to re-create the correct sequence for the original DNA strand. Students can then verify their work by comparing it to their partner's uncut strand.

  • Have students answer the following questions. Discuss in class, if desired.

    1. Summarize how restriction enzymes can be used to find the sequence of DNA. (They cut DNA at known patterns. The fragments created by various enzymes can then be compared, and over-lapped, thus indicating the sequence of DNA bases.)

    2. What are some of the differences between this simulated sequencing activity and real-world DNA sequencing? (Real samples of DNA would be much longer. We would not be able to see the individual bases like we could on our paper. We would have many more fragments. Etc.)

    3. How does the computer aid in DNA sequencing? (It greatly speeds up the process, by being able to rapidly recognize the repeating patterns and overlap the fragments into the proper sequences.)

    4. What is the value of sequencing DNA? (Knowing DNA sequences provides a basis for comparison and insight into which genes do what and where specific genes are located, perhaps leading to cures for genetic diseases, etc.)


  • Students' notes from the video.
  • Participation and success in sequencing activity.
  • Responses to follow-up questions.


  • Explore one of the Ethical, Legal, and Social Issues listed on the Human Genome Project Information site at and write a position paper reflecting students' views.

  • Research uses of restriction enzymes and create a poster or pamphlet to display the information.

  • Research and write a biography of one of scientists involved in the Human Genome Project.

  • Research and write a report on the history of genetic science:

Student Handouts:

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