Youreka Science: The Semi-Conservative Replication of DNA • iBiology

00:00:14.21 DNA is considered the molecule of life
00:00:16.23 and is now easily identified as a double helix.
00:00:21.02 However, figuring out its structure,
00:00:23.00 and how DNA works,
00:00:25.02 was not an easy task,
00:00:26.15 and just a little over 60 years ago
00:00:28.06 it was still a complete mystery.
00:00:30.18 Then, in 1953,
00:00:32.24 came Watson and Crick,
00:00:34.16 who, with the help from colleagues Rosalind Franklin and Maurice Wilkins,
00:00:38.14 discovered how the six billion base pairs
00:00:41.07 that make up our genetic material
00:00:43.02 are stored in the cell.
00:00:44.25 The DNA was actually a helix made of two strands.
00:00:48.07 This DNA was passed on from generation to generation
00:00:50.26 as a double helix.
00:00:53.00 Specific DNA bases,
00:00:54.20 which we call A, adenine; T, thymine;
00:00:57.16 G, guanine; and C, cytosine,
00:01:00.10 are found on both strands
00:01:02.25 and pair with each other in a conserved way.
00:01:05.16 A pairs with T, and G pairs with C.
00:01:10.20 Our DNA is made up of these four bases
00:01:12.18 in a variety of different orders
00:01:14.11 that code for all of life.
00:01:16.11 This is an amazing fact.
00:01:18.00 These four bases are the sole building blocks
00:01:20.11 for our six billion bases of genetic code,
00:01:23.23 which defines our identity as humans
00:01:26.01 and as individuals --
00:01:28.07 our height, hair color, disease susceptibility,
00:01:30.16 and much, much more.
00:01:32.17 Discovering the structure of DNA
00:01:34.19 was a very important first step
00:01:37.02 to understanding how this seemingly simple molecule
00:01:39.07 controls all of life.
00:01:40.27 However, one important question lingered.
00:01:42.20 When a cell divides,
00:01:45.05 the daughter cell will have the same DNA sequence
00:01:46.25 as the parental cell.
00:01:48.15 So, how does this happen?
00:01:50.01 How does one cell produce a second cell
00:01:51.21 with the same exact DNA sequence?
00:01:54.21 In other words, how does DNA replicate?
00:01:57.29 This is a fundamental question
00:01:59.18 that is the basis of life.
00:02:01.06 We all come from a single cell
00:02:03.05 that will produce an entire organism
00:02:05.04 with trillions of cells
00:02:06.25 that all have the exact same DNA sequence.
00:02:09.16 And we are able to have children that share our DNA,
00:02:12.05 because our eggs and sperm carry our DNA sequence.
00:02:15.22 Understanding how DNA replicates
00:02:17.23 and how all of our cells
00:02:19.23 can carry the same DNA sequence
00:02:21.12 is the basis for understanding development, inheritance,
00:02:24.24 heritability, and life.
00:02:27.09 In 1953, the question lingered.
00:02:30.06 How does DNA replicate?
00:02:31.27 There were a few theories -- three, actually.
00:02:34.24 One of them was conservative replication,
00:02:37.02 where a DNA molecule would get copied
00:02:39.23 and make a second, new, red DNA molecule.
00:02:43.01 The second was dispersive,
00:02:45.12 where the DNA molecule would be cut at various parts,
00:02:48.24 each of which would get copied -- here, in red --
00:02:51.20 and reattached to produce two DNA molecules.
00:02:55.14 And the third was semiconservative,
00:02:58.21 where two DNA strands would separate,
00:03:00.12 and each one would serve as a template to copy
00:03:02.22 a second, red strand,
00:03:04.11 thus producing two DNA molecules.
00:03:07.03 But which one was it?
00:03:08.24 Many scientists did not believe that two DNA strands
00:03:11.01 could separate
00:03:13.23 because of how strong a DNA molecule is,
00:03:15.10 so they were skeptical of the semiconservative model.
00:03:18.07 The only way to solve this was to create an experiment
00:03:20.15 to tell the new DNA strand from the old one.
00:03:25.08 So, two scientists, Matthew Meselson and Franklin Stahl,
00:03:28.24 had an idea to design an experiment
00:03:31.09 that would be known as the most beautiful experiment in biology.
00:03:35.13 Their findings are published in their article titled
00:03:37.29 "The replication of DNA in E. coli",
00:03:40.04 published in May 1958
00:03:42.12 in the Proceedings of the National Academy of Sciences.
00:03:45.24 These scientists used bacteria to answer the question of DNA replication,
00:03:49.04 since it could be easily grown in the laboratory.
00:03:51.29 They grew the cells in the presence of a specific type of nitrogen,
00:03:56.02 which is found in DNA,
00:03:58.00 that would make all of the DNA very heavy.
00:04:01.27 They used centrifugation,
00:04:03.25 which can separate things according to their weight.
00:04:06.07 Initially, all of the DNA in the cell was heavy
00:04:09.15 and was at the bottom of the tube,
00:04:11.05 since it was grown in heavy nitrogen.
00:04:13.28 Then, they started growing these cells
00:04:16.23 in the presence of light nitrogen
00:04:18.14 so all of the DNA made in subsequent cell divisions
00:04:20.20 would be lighter.
00:04:22.19 After one cell division,
00:04:24.04 the DNA was half as heavy,
00:04:25.24 so half of the DNA molecule contained heavy nitrogen
00:04:28.02 and the other half didn't.
00:04:30.12 This is not in line with the conservative DNA replication model,
00:04:33.28 which would predict that one molecule
00:04:36.12 would be all light and the other all heavy.
00:04:39.17 However, this is in line with the semiconservative
00:04:41.18 or the dispersive model.
00:04:43.21 After two cell divisions,
00:04:45.19 the DNA molecule was now either half heavy and half light
00:04:49.25 or entirely light.
00:04:51.14 So, this is now not in line with the dispersive model,
00:04:54.01 which would predict that the DNA after two cell divisions
00:04:56.29 would contain a mixture of heavy and light DNA.
00:05:00.17 Instead, this experiment agrees
00:05:02.27 with the semiconservative DNA replication model.
00:05:05.00 Every cell gets one old DNA strand
00:05:07.00 and one new one.
00:05:14.20 By discovering that two strands of DNA can separate
00:05:17.01 and provide the template for the production of two new strands,
00:05:20.10 Meselson and Stahl revolutionized genetics.
00:05:23.18 Scientists were very skeptical that this was even possible,
00:05:26.14 but Meselson and Stahl proved it
00:05:28.21 with a beautifully designed experiment.
00:05:31.04 They also went on to show that
00:05:33.20 heating DNA can cause the DNA strands to separate.
00:05:35.19 This simple concept is the basis
00:05:38.05 for an important technique we frequently use in the laboratory
00:05:40.15 called polymerase chain reaction,
00:05:42.03 which is used in genetic testing, forensics, and paternity tests.
00:05:48.15 Meselson and Stahl identified the fundamental process
00:05:51.17 by which our DNA gets passed on from cell to cell.
00:05:54.17 This is the basis for inheritance
00:05:56.17 and an essential part of our development
00:05:58.21 from a single cell to a complete organism
00:06:00.19 that maintains the same DNA sequence
00:06:02.15 in all of its cells.
00:06:04.13 This exciting finding
00:06:06.10 opened up many new doors and research avenues.
00:06:08.15 Because DNA is the command center of the cell,
00:06:10.18 we could now study how DNA gives orders
00:06:13.00 for the cell to follow.
00:06:14.16 What controls the ability of DNA to make protein?
00:06:17.22 How does one cell know it's a heart cell
00:06:19.27 and another cell know it's a liver cell,
00:06:22.05 if they all have the same DNA?
00:06:25.17 Now, DNA wasn't just a static double helix;
00:06:27.26 it was a molecule that was animated.
00:06:29.22 It could make more of itself.
00:06:31.06 It could instruct a cell to behave a certain way.
00:06:33.28 All of the secrets of biology were ready to be answered.
00:06:37.22 Today, we understand many of these questions.
00:06:39.25 We know that the process of DNA replication
00:06:42.08 is very complex,
00:06:43.19 with many proteins coming together to make this happen,
00:06:46.29 as well as proofreading and repair mechanisms
00:06:49.00 to make sure that DNA is properly copied.
00:06:52.10 We can even produce a heart cell from a skin cell.
00:06:55.00 We know what controls cell division,
00:06:56.29 and how we can stop or accelerate it.
00:07:01.17 We know what sorts of things can cause mutations, o
00:07:03.28 r changes in the DNA sequence,
00:07:05.16 and how that influences cell behavior,
00:07:07.09 such as in cancer.
00:07:10.13 It's amazing now to look back at this very fundamental finding
00:07:13.16 -- that DNA replicates in a semiconservative manner --
00:07:16.10 and see how it has revolutionized biology
00:07:18.15 and our appreciation for DNA.
00:07:23.19 This video has been provided to you by Youreka Science
00:07:26.21 and iBiology, bringing the world's best biology to you.

This Talk

Speakers: Frank Stahl, Youreka Science, Matthew Meselson

Audience:

General Public
Educators of H. School / Intro Undergrad
Student
Educators of Adv. Undergrad / Grad
Researcher
Educators

Recorded: September 2011

Talk Overview

In 1958, Matthew Meselson and Frank Stahl published the “most beautiful experiment” in biology, where they demonstrated that DNA undergoes semi-conservative replication. In this video, Youreka Science describes the experiments that led to this discovery and why understanding how DNA replicates is so important. This video is a complement to Matthew Meselson’s iBiology Discovery talk, where Meselson recalls the events that led him to meet Frank Stahl and to plan and execute these experiments.

Speaker Bio

Frank Stahl

Frank Stahl

Frank Stahl received his PhD at the University of Rochester, where he studied genetic recombination in phage. He performed postdoctoral studies at Caltech, during which he completed the famous Meselson-Stahl experiment, and joined the faculty at the University of Oregon in Eugene in 1959. He is now an emeritus faculty member who enjoys teaching and… Continue Reading

Youreka Science

Florie Mar

Youreka Science was created by Florie Mar, PhD, while she was a cancer researcher at UCSF. While teaching 5th graders about the structure of a cell, Mar realized the importance of incorporating scientific findings into classroom in an easy-to-understand way. From that she started creating whiteboard drawings that explained recent papers in the scientific literature… Continue Reading

Matthew Meselson

Matthew Meselson

Dr. Meselson has made important contributions to the areas of DNA replication, repair and recombination as well as isolating the first restriction enzyme. Currently, he is Professor of Molecular and Cellular Biology at Harvard University, where his lab studies aging in the model organism bdelloid rotifers. Meselson is also a long-time advocate for the abolition… Continue Reading

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