Before we dive in, here's a quick reminder of the DNA basics this lesson builds on.
One Nucleotide
DNA is a chain of nucleotides. The base is the "letter" that carries information.
The Double Helix
Two strands wind together. The bases connect the strands like rungs on a ladder — but which bases pair together? That's what this lesson answers.
The Four DNA Bases
A
Adenine
T
Thymine
G
Guanine
C
Cytosine
The big question this lesson answers: Those bases in the middle of the ladder — do they connect randomly, or do they follow a rule? And if there's a rule, why does it exist?
Phase 1 · The Mystery
Know one strand — know them both?
By the early 1950s, scientists had figured out that DNA was a double helix — two strands twisted around each other, with the bases pointing inward like rungs on a ladder.
They could sequence one strand and read its bases in order. But here's what was remarkable: knowing just one strand was enough to know the other — without ever looking at it.
A T C G G T A
Strand 1 — known
→
? ? ? ? ? ? ?
Strand 2 — figured out without looking
Think about it: What rule would DNA have to follow for this to be possible? If you know one strand, what would let you predict the other — every single time?
Your Prediction
Before we look at any evidence, make a guess. What rule do you think the bases follow that makes this possible?
Phase 2 · Chargaff's Evidence
A Scientist Found a Pattern. Can You?
In the 1940s, biochemist Erwin Chargaff spent years measuring the exact percentage of each DNA base (A, T, G, C) in organisms from different species.
His data puzzled everyone — until the pattern clicked. Study the table below carefully.
Organism
A %
T %
G %
C %
Human
30.9
29.4
19.9
19.8
Sea Urchin
32.8
32.1
17.7
17.3
Salmon
29.7
29.1
20.8
20.4
Wheat
28.1
27.4
22.7
21.8
E. coli
24.7
23.6
26.0
25.7
■ Teal = notice these together■ Amber = notice these together
Question 1 of 3
Looking at the table, what do you notice about the % of Adenine (A) compared to the % of Thymine (T)?
Question 2 of 3
What do you notice about the % of Guanine (G) compared to Cytosine (C)?
Question 3 of 3
This pattern holds true in humans, sea urchins, salmon, wheat, and bacteria. What does that suggest about the rule behind it?
💡
You just rediscovered Chargaff's Rules!
Chargaff's rules state: %A ≈ %T and %G ≈ %C in any DNA sample, in any organism.
But why? This pattern has to mean A and T are always paired together — and G and C are always paired together. But we still don't know the physical reason. That's next.
Phase 3 · The Shape-Fit Challenge
Why Those Pairs? It's About Shape.
DNA's double helix has a consistent width from top to bottom — like a ladder with rungs all the same length. This puts a physical constraint on which bases can pair up.
Purines (LARGE)
Apurine
Gpurine
Double-ring structure
Pyrimidines (SMALL)
Tpyrimidine
Cpyrimidine
Single-ring structure
Think About It First
Remember: the DNA double helix has a consistent width all the way down — every rung of the ladder is the same length.
Look at the two size categories above. What would happen to the width of the helix if two large bases (purine + purine) tried to pair up? What about two small bases (pyrimidine + pyrimidine)?
Purine + Purine
4 rings total
Pyrimidine + Pyrimidine
2 rings total
Purine + Pyrimidine
3 rings total
Based on what you see, which type of pairing keeps the helix width consistent?
The size constraint: Every base pair must be one purine (large) + one pyrimidine (small). This is what keeps the helix the same width from top to bottom.
That narrows our possible pairs to: A–T, A–C, G–T, or G–C. But which ones actually form? That's what the drag and drop will reveal.
One More Constraint: Hydrogen Bonds
Size gets us to "purine + pyrimidine." But there are two possible pairings left: A–C and G–T, or A–T and G–C.
Hydrogen bonds are the deciding factor. Bases must have matching hydrogen bond donors and acceptors to lock together:
A — T
2 hydrogen bonds
G — C
3 hydrogen bonds
A–C or G–T would have mismatched bond patterns and wouldn't hold. So the only valid pairs are A–T and G–C. Notice how that explains Chargaff's data exactly!
Drag & Drop: Build the Complementary Strand
The top strand is fixed. Drag bases from the bank to pair with each base on the top strand. You now know the rules — put them to work!
Strand 1
Apur
Tpyr
Gpur
Cpyr
Tpyr
|
|
|
|
|
Strand 2
?
?
?
?
?
Apurine
Tpyrimidine
Gpurine
Cpyrimidine
Tpyrimidine
Apurine
Gpurine
Cpyrimidine
💡 Tap a filled slot to clear it and return the base to the bank.
Phase 4 · Your Discovery
You Figured It Out. Now Say It.
Based on the evidence — Chargaff's data and the shape-fit constraint — write the base pairing rules in your own words before we show you the formal version.
State the Rules
✓ The DNA Base Pairing Rules
A
—
T
Adenine + Thymine 2 hydrogen bonds
G
—
C
Guanine + Cytosine 3 hydrogen bonds
Two reasons these pairs form:
1. Size fit — One purine (large) must pair with one pyrimidine (small) to keep the helix width constant.
2. Hydrogen bond matching — A and T have compatible bond patterns (2 bonds); G and C have compatible patterns (3 bonds). Other combinations don't fit.
Memory tricks:
🍎 Apple in the Tree — A pairs with T
🚗 Car in the Garage — C pairs with G
Phase 5 · Apply It
Put the Rules to Work
Four problems. Each one tests the rules differently. Work through them in order — later problems build on earlier ones.
Problem 1 of 4 · Complementary Strand
Given this DNA strand, what is the complementary strand?
Click the buttons to build the complementary strand:
📖
Worked Example
Before Problem 2, let's walk through a Chargaff calculation together step by step.
Given: Guanine (G) makes up 30% of the bases in a DNA sample. Find A, T, and C.
Step 1 · Use the base pairing rule
C pairs with G, so %C = %G.
Cytosine (C)
30%
=
Guanine (G)
30%
Step 2 · Find what's left for A and T
G + C together = 30% + 30% = 60%. All four bases must add up to 100%, so:
A + T = 100% − 60% = 40%
Step 3 · Split equally between A and T
A pairs with T, so %A = %T. Split the 40% equally:
Adenine (A)
20%
Thymine (T)
20%
Check: 20 + 20 + 30 + 30 = 100% ✓ The four percentages always add up to 100. Use that as your check every time.
Problem 2 of 4 · Chargaff Calculation
A scientist analyzes a DNA sample and finds that Adenine makes up 22% of the bases. Using the base pairing rules, fill in the blanks:
Adenine (A)
22%
Thymine (T)
%
Guanine (G)
%
Cytosine (C)
%
Problem 3 of 4 · Error Analysis
A student built a DNA model and made a mistake. Look at this pairing — something is wrong. What's the error and why does it matter?
G
—
T
⚠ Is this a valid pair?
Problem 4 of 4 · Chargaff Calculation
A scientist analyzes a DNA sample from a bacterium and finds that Cytosine (C) makes up 35% of the bases. Using the base pairing rules, fill in the blanks:
Cytosine (C)
35%
Guanine (G)
%
Adenine (A)
%
Thymine (T)
%
🎉
You cracked the DNA code!
Let's return to the mystery you started with — and close it out.
Phase 6 · Closure
Back to the Original Mystery
Remember the question from Phase 1: If scientists knew the order of bases on one strand of DNA, how could they figure out the other strand — without ever looking at it?
You now have the answer. Because A always pairs with T and G always pairs with C, the sequence of one strand completely determines the other. Every base on one strand has exactly one possible partner on the other.
That's what makes DNA such a reliable information system — the base pairing rules aren't just chemistry, they're the reason genetic information can be read, copied, and passed on with precision.
Exit Ticket — 3 Questions
These count! Answer each one before finishing.
Exit Q1 · Name the pairs
Which two statements about base pairing are correct? (Select both)
Exit Q2 · Sequence Prediction
Given the strand CGTAGCTA, build the complementary strand:
Exit Q3 · Explain the Why
In one or two sentences, explain why A can't pair with C in DNA.
📋 Check Your Answer
Here's a complete answer. Does yours cover the key ideas?
A can't pair with C because they fail both constraints: first, A and C are both the wrong combination for consistent helix width — you need one large base (purine) and one small base (pyrimidine), but more importantly, A and C have mismatched hydrogen bond patterns and can't form stable bonds with each other. Only A–T and G–C have the right shapes and matching bond donors and acceptors.
Does your answer mention at least one of these two reasons?
🧬
Investigation Complete!
You used real scientific evidence to discover one of biology's most important rules — the same way Chargaff, Watson, and Crick pieced it together.
🔬 Data Analyst
🧩 Pattern Finder
⚗️ Rule Maker
🧬 DNA Expert
What's next?
Your cells copy their entire DNA every single time they divide — that's about 3 billion base pairs, copied with almost no errors. The structure of the double helix and the base pairing rules you just discovered are exactly what make that possible. One strand serves as the template, and the rules guarantee the new strand is a perfect match. That process — DNA replication — is coming up next.
