Packaging DNA into the nucleus

Two metres in a nucleus

The length of a DNA double helix is the number of base pairs multiplied by the distance between two base pairs.

A human cell with two sets of chromosomes has $6.6 \times 10^9$ base pairs. Its DNA is $6.6 \times 10^9 \times 0.34 \times 10^{-9}\ \text{m} = 2.2\ \text{m}$ long. The nucleus is only a few micrometres wide. The DNA is hundreds of thousands of times longer than the nucleus is wide. It has to be packed.

Books print different sizes for the human genome, from 3.1 to 3.3 billion base pairs for one set of chromosomes. NCERT uses 6.6 billion for the two sets of a cell, and so does this course.

In bacteria

A bacterium has no nucleus. Its DNA lies in a region of the cell called the nucleoid. The DNA is a long circle. It is folded into large loops, and the loops are held by proteins. The DNA is also twisted on itself, which is called supercoiling. So the chromosome of E. coli, which is 1.56 mm long when stretched out, fits in a cell about 2 µm long.

In eukaryotes: the nucleosome

In the nucleus of a eukaryotic cell, the DNA is wound round proteins called histones.

• Histones are positively charged, because they are rich in two basic amino acids, lysine and arginine.
• DNA is negatively charged, because of its phosphate groups.
• The unlike charges attract. So the DNA winds closely round a core of 8 histone molecules, the histone octamer.

The core and the DNA round it make a nucleosome. A nucleosome holds about 200 base pairs of DNA. Under the electron microscope, a thread of nucleosomes looks like beads on a string. This thread is chromatin, so named because it takes up stain.

The beads on a string are only the first level. The thread is coiled into a chromatin fibre, and the fibre is folded again. At each level the packing needs more proteins. They are the non-histone chromosomal proteins (NHC proteins). At metaphase, the DNA is packed into the dense chromosomes that you can see under a light microscope.

This part is not in the NEET syllabus, but A-Level and IB ask it: the core has two each of the histones H2A, H2B, H3 and H4. About 147 base pairs wind round the core in 1.65 turns, and the rest, the linker DNA, joins one bead to the next. A fifth histone, H1, sits on the linker. The bead is about 11 nm across.

Loose and tight chromatin

Look at a stained nucleus. Some regions are pale and some are dark.

• Euchromatin is loosely packed and stains lightly. It is transcriptionally active, which means its genes are being read.
• Heterochromatin is tightly packed and stains darkly. It is usually not active.

You should find that the length of the DNA grows in a straight line with the number of base pairs, and that a human cell reaches about 2.2 m.

Try it in Python

The program finds the length, the turns and the nucleosomes of a chromosome.

Practise with new numbers

Common mistakes

• Saying that histones are negatively charged. They are positive. The DNA is negative.
• Saying that a nucleosome has 8 base pairs. It has 8 histone molecules and about 200 base pairs.
• Saying that heterochromatin is the active chromatin. Euchromatin is active.
• Saying that bacteria have a nucleus. Their DNA lies in a nucleoid.
• Forgetting the unit. The length of DNA is in nm, mm or m, and the base pairs are only a count.

Remember these

• Length of DNA equals base pairs times 0.34 nm. A human cell has about 2.2 m.
• Bacteria: nucleoid, DNA in loops with proteins, supercoiled.
• Eukaryotes: positively charged histones, a core of 8, about 200 base pairs, the nucleosome. Beads on a string, the chromatin.
• The NHC proteins help to pack the chromatin further. Euchromatin is loose and active. Heterochromatin is tight and inactive.

Check yourself

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

1. How long is a DNA of 6.6 billion base pairs?

2. Why do histones bind to DNA?

3. What is a nucleosome made of, and how many base pairs does it hold?

4. Which is the active chromatin, euchromatin or heterochromatin?

5. How is the DNA of a bacterium packed, if there is no nucleus?

References

• NCERT (2023). Biology, Textbook for Class XII, chapter 5, Molecular Basis of Inheritance.
• Clark M. A. et al. (2018). Biology 2e, OpenStax, chapter 14, section 14.2, DNA Structure and Sequencing.
• Luger K. et al. (1997). Crystal structure of the nucleosome core particle at 2.8 angstrom resolution. Nature, 389, 251 to 260.