The double helix, base pairing and hormones

Watson and Crick's model

In 1953, James Watson and Francis Crick proposed a structure for DNA. They used the X-ray pictures of Rosalind Franklin and Maurice Wilkins, and Chargaff's rules. Their model has these features:

• Two strands wind round the same axis in a right-handed double helix.
• The strands run in opposite directions: one from 5′ to 3′, and the other from 3′ to 5′. We say they are antiparallel.
• The sugar and phosphate backbone is outside. The bases are inside, with their flat faces stacked like a pile of coins.
• Each base pairs with a base on the other strand, through hydrogen bonds.

Base pairing

A purine is always paired with a pyrimidine. This keeps the width of the helix the same, about 2 nm. Two purines would be too wide, and two pyrimidines too narrow. The shape and the hydrogen-bonding groups of the bases allow only two pairs:

• Adenine with thymine: two hydrogen bonds.
• Guanine with cytosine: three hydrogen bonds.

This explains Chargaff's rules. Every A has a T opposite it, and every G has a C. So the amounts are equal. It also shows why the two strands are complementary. If one strand reads 5′-ATGC-3′, the other reads 3′-TACG-5′ across from it. Reading it from 5′ to 3′, we write 5′-GCAT-3′.

Dimensions of the helix

In B-DNA, the form in cells, the base pairs are 0.34 nm apart along the axis. There are about 10.5 base pairs in a turn, so one turn is $10.5 \times 0.34 = 3.57\ \text{nm}$ long. Watson and Crick used 10 base pairs and 3.4 nm for a turn in their first model. Later measurements gave 10.5.

Because the numbers are so small, the molecule is very long. One set of the human chromosomes holds $3.1 \times 10^9$ base pairs. Its length is $3.1 \times 10^9 \times 0.34\ \text{nm} = 1.05\ \text{m}$. A cell has two sets, so about 2 m of DNA is packed into a nucleus a few micrometres wide.

Try 3000 base pairs and then 6000. The length doubles. Now change the pairs in a turn from 10.5 to 10. The number of turns rises and the length of one turn falls. The total length does not change, because it depends only on the rise of 0.34 nm.

Copying the information

Because each strand holds the information of the other, a cell can copy its DNA. The strands separate. Each strand is used as a template to build a new partner by base pairing. The result is two identical double helices, each with one old and one new strand. This is semi-conservative replication.

RNA and the genetic code

RNA is made by copying one strand of DNA. It differs from DNA in its sugar, in having uracil, and in usually being a single strand. There are three main kinds:

• Messenger RNA (mRNA) carries the message from DNA to the place where protein is made.
• Transfer RNA (tRNA) brings the amino acids.
• Ribosomal RNA (rRNA) is part of the ribosome, the machine that makes protein.

The message is read in groups of three bases, called codons. Four bases in groups of three give $4^3 = 64$ codons. Of these, 61 code for amino acids and 3 are stop signals. The codon AUG codes for methionine and starts a protein. Several codons can code for the same amino acid, so the code is degenerate.

A change of one base can change a protein. In sickle-cell anaemia, the codon GAG for glutamic acid has become GUG, for valine, in one chain of haemoglobin.

Hormones

Hormones are chemical messengers. A gland makes them and releases them into the blood. They act on target cells far away, in very small amounts. They are made by the body, which is how they differ from vitamins. They are not catalysts, which is how they differ from enzymes. They fall into three groups by structure.

• Steroids: testosterone, oestradiol, progesterone and cortisol. They have four fused rings and are made from cholesterol. They are fat-soluble.
• Peptides and proteins: insulin, glucagon, oxytocin and vasopressin. Insulin has 51 amino acids in two chains. Oxytocin has 9.
• Amino acid derivatives: adrenaline, which comes from tyrosine, and thyroxine, which contains iodine.

The steroid nucleus has 17 carbon atoms in three six-membered rings and one five-membered ring. A steroid hormone dissolves in fat, so it crosses the cell membrane and acts inside the cell. A peptide hormone does not cross the membrane. It binds a receptor on the surface of the cell.

Some hormones, and what happens when they are lacking:

• Insulin lowers the level of glucose in blood. Without enough, the result is diabetes. Glucagon has the opposite effect.
• Thyroxine controls the rate of metabolism. Thyroxine has 4 iodine atoms, which make up $65.3\%$ of its mass. A lack of iodine in the diet gives goitre, a swelling of the thyroid gland.
• Adrenaline prepares the body for action, by raising the heart rate and the level of glucose.
• Testosterone and oestradiol control the sexual development of male and female bodies.
• Cortisol and aldosterone come from the cortex of the adrenal gland. A lack of them is Addison's disease.

Practise with new numbers

Try it in Python

The program reads a short gene. It copies the coding strand into messenger RNA, and reads the codons until a stop codon appears. The table has only a few codons.

Common mistakes

• Pairing A with C or G with T. A pairs with T, and G with C.
• Reading the partner strand in the same direction. The strands are antiparallel.
• Thinking all codons code for amino acids. Three are stop signals.
• Thinking that a hormone is an enzyme. A hormone is a messenger.

Remember these

• DNA is a double helix of two antiparallel strands. A pairs with T (2 hydrogen bonds). G pairs with C (3).
• B-DNA: 0.34 nm between base pairs, about 10.5 pairs and 3.57 nm per turn, 2 nm wide.
• RNA has three main kinds. A codon is three bases, and there are 64 of them.
• Hormones are steroids, peptides or amino acid derivatives. Insulin: diabetes. Thyroxine and iodine: goitre.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. One strand of DNA reads 5′-GATTACA-3′. What does the partner strand read from 5′ to 3′?

2. Why must a purine always pair with a pyrimidine in DNA?

3. A mRNA has 90 bases, of which the last three are a stop codon. How many amino acids does the protein have?

4. Why does a steroid hormone act inside the cell, and a peptide hormone on its surface?

References

• Nelson and Cox, Lehninger Principles of Biochemistry, 8th edition, Chapter 8 (the double helix, B-DNA dimensions) and Chapter 23 (hormones).
• NCERT Chemistry for Class 12, Part II, the chapter Biomolecules (nucleic acids, hormones).
• Watson and Crick, Nature 171, 737 to 738 (1953).