Biology · Unit 4: DNA and inheritance

How the DNA Model Was Built

How did scientists build a model of a molecule too small to see, and how did reading whole genomes change biology? You compare four models of DNA, follow the evidence that led to the double helix in 1953, and read real data on how the cost of sequencing a genome fell. Afterwards you can say what each DNA model shows and hides, and make a claim from cost data.

Where this lesson sits

  • Virginia SOL BIO.5b
  • Practices BIO.1c, BIO.1d, BIO.1e, BIO.1f

Essential question: How has our model of DNA changed over time, and how did reading whole genomes change biology?

  1. Life Science (grade 7) LS.10 a

    Review it at grade 7 level

    In grade 7 you learned that DNA is a double helix, shaped like a twisted ladder. The sides of the ladder are the same in all living things. The rungs are pairs of bases, written A, T, C and G. The order of the bases forms a code for making proteins, and proteins affect traits. You also learned that many people, over many years, added discoveries that built our current understanding of DNA. Biology adds how that model was built from evidence, and how scientists now read the order of all the bases in a genome.

  2. Biology BIO.5b You are here

    This lesson

  3. Biology II Biology II: Genetics, GEN.7 b

    Preview where it goes next

    Virginia’s Biology II: Genetics course asks what the Human Genome Project made possible. The project provided data needed to read and edit the human genome. With a reference sequence, scientists can compare a person’s DNA with it and find differences. Those comparisons are used in forensics to match DNA samples, in personalized medicine to choose care that fits a person’s genes, and in genetic counseling to help families understand inherited risks. This lesson left out those uses, and also how editing tools find a target sequence. Each of those depends on first knowing the order of bases in the region being studied.

  4. College

Watch first Every DNA Model Leaves Something Out · 2:57

Supports

Supports change how much help you get, not what you learn.

The Human Genome Project spent about 13 years, from 1990 to 2003, reading the DNA of humans. By 2022, the estimated cost to sequence a human-sized genome had fallen to about 525 dollars. Nobody has ever looked at DNA the way you look at a pencil. Most of what we know about its shape and its letters comes from indirect evidence and from models. How was the model of DNA built, and what changed when scientists could read whole genomes?

What do you think? Decide before you read.

  1. Watson and Crick discovered DNA.

    Scientists disagree: DNA was identified by Friedrich Miescher in 1869, in material from the nuclei of white blood cells. In 1953 Watson and Crick proposed a model of how DNA is shaped. Their model used measurements that other scientists had already made, so it was the result of many people’s work.

    What scientists think

    Scientists disagree: DNA was identified by Friedrich Miescher in 1869, in material from the nuclei of white blood cells. In 1953 Watson and Crick proposed a model of how DNA is shaped. Their model used measurements that other scientists had already made, so it was the result of many people’s work.

  2. A scientific model is a perfect copy of the real thing.

    Scientists disagree: Every model makes approximations. A flat ladder drawing of DNA removes the twist. A string of letters gives the order of bases but no shape. Scientists choose a model by asking what it is meant to explain, and they keep in mind what it leaves out.

    What scientists think

    Scientists disagree: Every model makes approximations. A flat ladder drawing of DNA removes the twist. A string of letters gives the order of bases but no shape. Scientists choose a model by asking what it is meant to explain, and they keep in mind what it leaves out.

  3. The Human Genome Project read the DNA of one single person.

    Scientists disagree: The first human reference sequence was a patchwork of DNA from several anonymous donors, with about 70 percent from one person. It works as a reference, a standard to compare against, rather than as a record of any one person. Later projects added sequences from many more people to show how human DNA varies.

    What scientists think

    Scientists disagree: The first human reference sequence was a patchwork of DNA from several anonymous donors, with about 70 percent from one person. It works as a reference, a standard to compare against, rather than as a record of any one person. Later projects added sequences from many more people to show how human DNA varies.

Explore: compare four models of one molecule

In the simulation you switch between four models of DNA: a flat ladder, a twisted helix ribbon made of blocks, a string of base letters, and a chromosome view. For each model, you tick boxes to show what it can explain: base pairing, copying, how much information DNA holds, and how DNA packs into a cell. The simulation then shows what each model hides.

Compare four models of DNA⚙ original · interactive

Step 1. Tick what you think this model can explain.

Flat ladder: pick it, tick the boxes you think fit, then check.

All models side by side (a model fills in after you check it)
ModelPairingCopyingInformationPacking

In this sketch each model is judged by what the lesson says each model shows and leaves out, plus our own reading. Blocks and letters are not to scale, and no atoms are drawn.

Rule to keep: every DNA model shows some features and hides others, so scientists pick the model that fits the question.

Try this.

  1. Before you open the ladder model, predict which of the four questions it can answer. Then check the boxes and compare.
  2. Predict which model is best for comparing your DNA with a classmate’s at one gene. Test your choice.
  3. Switch to the chromosome view. Predict whether you can still see base pairs. Look and explain what you notice.
  4. Pick the one model you would keep if you could keep only one. Write what you would lose.

Explain: every DNA model leaves something out

  • model
  • nucleotide
  • base pairing
  • double helix
  • X-ray diffraction
  • DNA sequencing
  • genome
  • Human Genome Project
  • chromosome
  • reference sequence

A model is a simplified representation that helps explain or predict something real. A city map is a model: it shows streets but not the people on them.

DNA is built from units called nucleotides. A nucleotide is one building block of DNA, made of a sugar, a phosphate group and a base. DNA has four bases, written A, T, G and C. The order of the bases carries the instructions, as the DNA structure lesson shows.

Each common model of DNA is good at one job:

ModelGood for showingLeaves out
Flat ladder with lettersWhich bases pair, and the two backbonesThe twist, and all the atoms
Double helix ribbonHow two strands coil around each otherIndividual atoms, and often the actual base order
Base-letter string (ATTGC…)The order of bases, for comparing DNAShape, size and the partner strand
Space-filling modelHow much space the atoms fillBase pairs hidden inside the molecule

These are four pictures of one substance, not four kinds of DNA. The map analogy breaks down in one way: a map is drawn from a place you can visit and see. A DNA molecule is only about 2 nanometers wide, far too narrow to see with your eyes or a light microscope, so DNA models are built from measurements.

Key idea: Each DNA model shows some features and hides others, so scientists pick the model that fits the question.

Explain: three kinds of evidence, one model

DNA was identified in 1869, long before anyone knew its shape. By the early 1950s, scientists had three kinds of evidence to work with.

  • Base amounts. Chemists broke DNA into its bases and measured each one. Erwin Chargaff’s group found that in a DNA sample, the amount of A is close to the amount of T, and G is close to C. Other teams showed that the four bases do not simply come in equal amounts in every species.
  • X-ray patterns. In X-ray diffraction, X-rays shone through lined-up DNA fibers scatter into a pattern of spots on film. Rosalind Franklin and Raymond Gosling measured such patterns, including one often called Photo 51. The spacing of the spots pointed to a helix about 2 nanometers wide, with phosphates on the outside. The pattern gave shape clues, not a photograph of the bases.
  • Model building. James Watson and Francis Crick fitted these facts together with the known chemistry of the parts. Their paper said they had been stimulated by knowing the general nature of unpublished results and ideas from Maurice Wilkins, Franklin and their coworkers at King’s College London.

The result, published on 25 April 1953, was the double helix: two strands of DNA coiled around each other, running in opposite directions, with the backbones outside and bases inside. Base pairing is the rule that A pairs with T and G pairs with C across the two strands. That rule explained the equal amounts of A and T. It also suggested how DNA could be copied, because each strand fixes the order of its partner.

AI-generated illustration: three panels. Left, a tube of DNA beside four piles of base blocks in two matching pairs. Middle, an X-ray beam passing through a bundle of lined-up fibers onto a film sheet that shows a cross of spots. Right, the double helix model those clues were fitted into. Five numbered circles mark the parts.
  1. Base amounts
  2. X-rays
  3. lined-up DNA fibers
  4. pattern of spots
  5. double helix
  2. X-rays
  5. double helix

Word bank: Base amounts, lined-up DNA fibers, pattern of spots

Check your labels
  1. Base amounts
  2. X-rays
  3. lined-up DNA fibers
  4. pattern of spots
  5. double helix
Three kinds of evidence, one model: base amounts and an X-ray pattern were fitted together into the double helix. Name the five numbered parts.

The authors were careful. Watson and Crick called their model unproved until it could be checked against more exact results. Franklin and Gosling called a helix highly probable. Later experiments tested the model and supported it.

Key idea: The double helix model was built to fit base-amount data, X-ray measurements and chemistry together, and later tests supported it.

Explain: reading the letters since 1977

Knowing the shape did not tell anyone the order of the bases. DNA sequencing is any method that reads the order of bases in a piece of DNA. In 1977 Frederick Sanger and his colleagues published a method that stops copies of a strand at each kind of base. The lengths of the copies reveal the base order.

AI-generated illustration: a row of eight coloured blocks for the strand being read, and below it a staircase of eight copies from one to eight blocks long, each ending in a coloured stop block. Read from shortest to longest, the stop colours repeat the strand's order.
The idea behind Sanger's 1977 method: copies of a strand stop at each base, and their lengths reveal the order of the bases.

A genome is all the DNA in one set of an organism’s chromosomes. A chromosome is one long DNA molecule wound with proteins. A human genome has about 3 billion base pairs.

The Human Genome Project was an international project, from October 1990 to April 2003, that read the order of bases in human DNA. It mostly used improved Sanger sequencing. Human chromosome 22 was the first finished human chromosome, published in 1999. The project produced a reference sequence, a standard human DNA sequence that other sequences are compared against. It was pieced together from several donors, and it still had gaps.

Newer methods kept going. In 2022 a team reported a human sequence with no gaps in the 22 numbered chromosomes and the X, and a finished Y followed in 2023. In 2023 another team released a draft “pangenome” built from 47 people, to show how human DNA varies. The double helix model still holds. Sequencing added the letters, how many there are, and how they differ between people.

Key idea: Sequencing reads the order of DNA bases, and since 1990 it has grown from single chromosomes to whole human genomes.

Elaborate: the falling cost of a genome

DateEstimated cost per human-sized genome (US dollars)
September 200195,263,072
October 200340,157,554
October 20077,147,571
January 20083,063,820
January 201046,774
April 20125,901
July 20151,363
May 2019606
August 2021562
May 2022525

These values come from the National Human Genome Research Institute (NHGRI) “Cost per Genome” data table, May 2022 version (genome.gov). They are production costs at NHGRI-funded sequencing centers, scaled to a genome of 3,000 million bases. They leave out the cost of interpreting the DNA, and they are not prices a person pays. For comparison, NHGRI reported the whole U.S. part of the Human Genome Project at about 2.7 billion dollars, counted in 1991 dollars, which paid for much more than sequencing.

  1. Between which two neighboring dates did the cost fall the most, compared with its starting value?
  2. About how many times cheaper was May 2022 than September 2001?
  3. Compare 2019 to 2022 with 2008 to 2010. What do you notice about the recent change?

Claim, evidence, reasoning

Make a claim that answers the essential question: how did reading whole genomes change what biologists can study? Use this data.

Start with: The data show that the cost of sequencing a genome , so biologists can now .

Start with: In September 2001 one genome cost about , but by May 2022 it cost about .

Start with: If each genome costs less, the same budget pays for genomes, which lets scientists compare .

Compare with a model answer

The cost of sequencing a human-sized genome fell so far that biologists can now compare many genomes instead of one reference. In September 2001 NHGRI estimated about 95 million dollars per genome. By May 2022 the estimate was about 525 dollars, roughly 180,000 times cheaper. In this table, the steepest fall came between early 2008 and early 2010, from about 3 million dollars to about 47,000 dollars. With a fixed budget, a lower cost per genome pays for many more genomes, so scientists can compare DNA across many people and species. One limit: these are production costs from funded sequencing centers only, and they leave out the cost of analyzing the data.

Design problem

Sequencing machines read short pieces of DNA, and a computer joins overlapping pieces back together. Repeated stretches make this hard. Plan an investigation with paper strips to test whether longer pieces make it easier to rebuild a sequence that contains a repeat.

One way to do it

Write a 60-letter made-up DNA sequence that contains the same 8-letter stretch twice. Make several copies and cut them into overlapping strips.

  • Independent variable: strip length, such as 6, 12 and 20 letters.
  • Dependent variable: whether a classmate who has not seen the original rebuilds it correctly, and how long it takes.
  • Constants: the same original sequence, the same number of copies, and a cut at random places each time.
  • Control: a version with no repeated stretch, cut into 6-letter strips, to show the puzzle is solvable without a repeat.
  • Trials and sample size: at least five classmates for each strip length, each working alone.

If short strips often give the wrong order around the repeat while 20-letter strips do not, longer reads help. This is one reason long-read methods helped fill gaps in 2022. A limit: paper strips have no reading errors, and real sequencers make some.

Evaluate: check your thinking

The human genome took about 13 years to read partly because the methods of the time were slow and costly. New sequencing technology cut the estimated cost from about 95 million dollars in 2001 to about 525 dollars in 2022. The double helix model from 1953 still holds, and cheap sequencing now lets biologists compare the DNA of many people and species.

Science practices you used: comparing models and naming their limits, tracing how evidence built a model, reading a data table and calculating a ratio, and planning a fair test with repeated trials.

How we measure it

X-ray fiber diffraction

X-rays are shone through a bundle of lined-up DNA fibers, and the spots they make on film are measured. The spacing of the spots gives clues to repeat distances and overall shape, but it does not show the order of the bases.

Base-composition analysis

DNA is broken into its bases with acid, and the amount of each base is measured. Comparing the amounts tests ideas about how the bases are arranged, such as whether A and T come in equal amounts.

Sanger chain-termination sequencing

An enzyme copies a DNA strand while special building blocks stop each copy at a known base. Sorting the copies by length reveals the base order, one letter at a time.

Finish line

Test yourself

8 questions

Practice and MCAT-style, with explained answers.

Next · Lesson 18

From DNA to Protein

How can changing one letter out of hundreds in a gene make red blood cells bend into stiff sickle shapes?

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← Lesson 16 · DNA: Structure and Copying

B-form DNA, a short double helix seen as a 3D model
B-form DNA, a short double helix seen as a 3D model ● LIVE · RCSB PDB 1BNA
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Loading live structure 1BNA from RCSB PDB…

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Rosalind Franklin and Raymond Gosling

Rosalind Franklin and Raymond Gosling

Recorded and analyzed X-ray diffraction patterns of DNA fibers from calf thymus, showed that the fibers take different forms as humidity changes, and concluded that the B form was very probably a helix with its phosphate groups on the outside.

Rosalind Franklin and Raymond Gosling worked with thin fibers pulled from DNA that had been purified from calf thymus. They shone X-rays through the fibers and recorded the patterns of spots the rays made on film. They found that the same DNA gave two different patterns as the air around it got wetter or drier, so the way a sample is prepared matters. From the wetter form, called the B form, they measured a repeat of about 3.4 nanometers along the fiber and a width of about 2 nanometers. They wrote that a helix was highly probable, a careful word for strong but indirect evidence. Their paper appeared in Nature in April 1953, in the same issue as the double helix model. Measurements like theirs let any model of DNA be checked against real numbers.

✓ verbatim Franklin and Gosling, Molecular configuration in sodium thymonucleate, Nature 171:740-741 (1953), doi:10.1038/171740a0.
Frederick Sanger

Frederick Sanger

With Nicklen and Coulson, published in 1977 a way to read the order of bases in DNA by stopping the copying of a strand at each kind of base.

By the 1970s, biologists knew DNA was a double helix, but reading the order of its bases was slow and hard. Frederick Sanger and his colleagues Nicklen and Coulson found a faster way. They let an enzyme copy a DNA strand in a test tube. They also added a small amount of altered building blocks that stop the copy as soon as one is added. The result is a mix of copies that end at different places, and their lengths reveal where each base sits. They first used the method on DNA from a virus that infects bacteria, not on human DNA. They published it in 1977. The Human Genome Project later used improved versions of this chain-stopping idea to read human chromosomes.

✓ verbatim Sanger, Nicklen and Coulson, DNA sequencing with chain-terminating inhibitors, PNAS 74:5463-5467 (1977), doi:10.1073/pnas.74.12.5463.
Test yourself
Question 1 of 8 Score 0 / 0

In the base-pairing rule of the double helix model, adenine (A) on one strand pairs with which base on the other strand?
Sources & Integrity

Every structure, slide, simulation, and clip on this page is listed below with the source it came from. None of the 3D structures is drawn by hand or by AI: each one loads by accession ID from RCSB PDB or PubChem. This panel is generated from the lesson's own data file, so what it lists is what the page loads.

Molecular structures live data

  • B-form DNA, a short double helix seen as a 3D model — RCSB PDB 1BNA · coordinates CC0 · a 12-base-pair B-DNA double helix (Dickerson dodecamer)

Simulations

  • Compare DNA models · Original interactive — Biochemistrypedia (Deppmann Lab).

Scientist profiles & quotes

  • Rosalind Franklin and Raymond Gosling — Franklin and Gosling, Molecular configuration in sodium thymonucleate, Nature 171:740-741 (1953), doi:10.1038/171740a0.
  • Frederick Sanger — Sanger, Nicklen and Coulson, DNA sequencing with chain-terminating inhibitors, PNAS 74:5463-5467 (1977), doi:10.1073/pnas.74.12.5463.

Quotes are verbatim from the cited source. Profile text is original to this site and was checked against the sources cited.

Animated explainer

Every DNA Model Leaves Something Out · narration: an AI narrator voice (Gemini, Charon) reading narration written from this lesson's text · animation: AI-generated in code (Manim) by Claude, a schematic with no drawn molecular structures, plots computed from their equations · captions from the narration script.

Images & figures

2 illustrations in this lesson are AI-generated: drawn by an image model from a written spec, then checked by a separate AI judge against the spec and the lesson text. None shows a chemical structure or data.

  • three panels. Left, a tube of DNA beside four piles of base blocks in two matching pairs. Middle, an X-ray beam passing through a bundle of lined-up fibers onto a film sheet that shows a cross of spots. Right, the double helix model those clues were fitted into. Five numbered circles mark the parts.
  • a row of eight coloured blocks for the strand being read, and below it a staircase of eight copies from one to eight blocks long, each ending in a coloured stop block. Read from shortest to longest, the stop colours repeat the strand's order.

Every 3D structure is rendered live from an accession ID, and every plot is drawn from its equation in the browser.

integrity Machines check the mechanics. The build confirms that every local file exists, that every question's answer key points at a real choice, and that any AI-generated scientific figure names the person who checked it; a weekly job re-resolves every accession ID against its database. Questions are original; MCAT-style items are written for this site and are not real AAMC questions. Banned sources (the Tymoczko textbook, publisher decks, copyrighted figures) are not used.

Life Science (grade 7)

In grade 7 you learned that DNA is a double helix, shaped like a twisted ladder. The sides of the ladder are the same in all living things. The rungs are pairs of bases, written A, T, C and G. The order of the bases forms a code for making proteins, and proteins affect traits. You also learned that many people, over many years, added discoveries that built our current understanding of DNA. Biology adds how that model was built from evidence, and how scientists now read the order of all the bases in a genome.
Biology

DNA is too small to see directly, so scientists understand it through models, and each model shows some features and hides others. The double helix model of 1953 was built to fit several kinds of evidence: base amounts measured in DNA samples, which showed A about equal to T and G about equal to C, X-ray diffraction patterns that pointed to a helix of a certain width, and the chemistry of the parts. Its base pairing suggested how DNA could be copied. Since 1977, sequencing methods have read the order of the bases. The Human Genome Project, from 1990 to 2003, used improved Sanger sequencing to build a human reference sequence. Falling costs now let biologists compare many genomes.
Biology II

Virginia’s Biology II: Genetics course asks what the Human Genome Project made possible. The project provided data needed to read and edit the human genome. With a reference sequence, scientists can compare a person’s DNA with it and find differences. Those comparisons are used in forensics to match DNA samples, in personalized medicine to choose care that fits a person’s genes, and in genetic counseling to help families understand inherited risks. This lesson left out those uses, and also how editing tools find a target sequence. Each of those depends on first knowing the order of bases in the region being studied.
College

A college course treats the double helix as the answer to a question about inheritance: it first asks how experiments showed that DNA, not protein, carries genetic information, and then how the structure explains copying. The linked lesson on DNA as the genetic material covers those experiments and the base-composition rules. The linked lesson on sequencing and genomes covers how methods read base order: Sanger chain termination, the massively parallel short-read methods that drove costs down after about 2008, and long-read methods that span repeated regions. It also covers assembly, which joins overlapping reads into chromosomes, and why the 2022 telomere-to-telomere reference filled gaps that the 2003 reference left open.
One chromosome first

Before a whole human genome was finished, an international team published the sequence of one chromosome, human chromosome 22, in December 1999. They read the euchromatic part of the chromosome, which holds most of its genes, about 33.4 million bases. The sequence was not one unbroken string. It came in 12 long pieces with gaps between them. Even with gaps, the team showed that reading a whole human chromosome was possible, and the public project’s work on the rest of the genome followed the same mapped, piece-by-piece approach.

— Dunham and colleagues, The DNA sequence of human chromosome 22, Nature 402:489-495 (1999), doi:10.1038/990031.
Filling the gaps, twenty years later

The human reference sequence announced in 2003 still had gaps where the DNA repeats itself too much for the methods of the time. In 2022 a team called the Telomere-to-Telomere consortium combined two newer kinds of sequencing that read much longer pieces. They reported a sequence of about 3.055 billion bases with no gaps in the 22 numbered chromosomes and the X, adding nearly 200 million bases missing from earlier references. The Y chromosome was finished separately in 2023, from a different person’s DNA.

— Nurk and colleagues, The complete sequence of a human genome, Science 376:44-53 (2022), doi:10.1126/science.abj6987.

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