What is a chromosome? How DNA is packed and passed on

A chromosome is a single, very long molecule of DNA wound around proteins, packed so that it fits inside a cell and can be copied and shared out when the cell divides. Humans have 46 chromosomes in most cells, arranged in 23 pairs: one of each pair from the mother, one from the father. Together they hold about 2 meters of DNA in a nucleus a few thousandths of a millimeter across.

In short

• Each chromosome is one DNA molecule, carrying hundreds to thousands of genes, wrapped around spool-like proteins called histones.
• People have 22 pairs of numbered chromosomes plus two sex chromosomes, usually XX or XY.
• Having an extra or missing chromosome changes the dose of many genes at once, which is why it usually has large effects.

What is a chromosome made of?

A chromosome is DNA plus protein, a combination called chromatin. The U.S. National Human Genome Research Institute's fact sheet on chromosomes describes each one as a single molecule of DNA wrapped around spool-like proteins, the histones. The name comes from the Greek for "colored body," because chromosomes soak up the dyes researchers use and show up clearly under a microscope when a cell is about to divide.

Each chromosome carries many genes, strung along its length between long stretches of DNA that don't code for proteins. Two special regions matter for how it behaves. The centromere is a pinched point where the two copies of a chromosome are held together after it has been duplicated, and where the cell's pulling fibers attach during division. The telomeres are repeated stretches at each end that protect the chromosome, as the plastic tips of shoelaces stop them fraying. In many kinds of cell, telomeres shorten a little at each division.

How does 2 meters of DNA fit in a cell?

By winding and folding, level after level. The NHGRI says that if all the DNA in one human cell were unwound and laid end to end, it would stretch about 6 feet, roughly 2 meters, as the DNA note also explains. The nucleus holding it is only about 6 micrometers (thousandths of a millimeter) across.

To feel the scale, enlarge everything until the nucleus is the size of a tennis ball, about 6.7 centimeters across.

1. The enlargement factor is 6.7 centimeters ÷ 6 micrometers, about 11,000.
2. The DNA, 2 meters long, becomes about 2 × 11,000 = 22,000 meters: a thread 22 kilometers long.
3. The double helix, about 2 nanometers wide, becomes about 22 micrometers wide, thinner than most human hairs.

So the problem a cell solves is packing 22 kilometers of thread finer than a hair into a tennis ball, without tangling it, while keeping the parts it needs readable.

The packing, from smallest to largest, works like this.

1. The double helix: two strands of DNA, about 2 nanometers wide.
2. Nucleosomes: about 150 base pairs of DNA wrap around a core of eight histone proteins, the NHGRI's glossary entry on the nucleosome explains, and the next stretch of DNA links to the next core. Under an electron microscope, this looks like beads on a string, about 10 nanometers wide.
3. Loops and folds: the string of nucleosomes folds on itself and is gathered into loops anchored to protein scaffolds. Genes in use sit in looser, open regions; unused ones are packed more tightly.
4. The visible chromosome: before a cell divides, each chromosome condenses much further into the compact, X-shaped form seen in textbook photographs. The X is a chromosome that has already been copied: two identical sister chromatids joined at the centromere.

The tidy staircase is a simplification. Older textbooks show a neat "30-nanometer fiber" between the beads and the loops; more recent imaging suggests that in living cells, chromatin is a more irregular, crowded tangle at that scale. And most of the time, outside cell division, chromosomes are not X-shaped at all but loose threads, each occupying its own region of the nucleus.

What are sex chromosomes?

Of the 23 pairs in human cells, 22 are autosomes, numbered 1 to 22 roughly from largest to smallest. The 23rd pair are the sex chromosomes. Most females have two X chromosomes and most males have an X and a Y. The Y carries a gene called SRY that starts the development of testes in an embryo; without it, development follows the other path.

Because the X is much larger than the Y and carries many genes the Y lacks, conditions caused by a variant on the X, such as red-green color blindness and hemophilia, are more common in males, who have no second X to cover for it. In females, one of the two X chromosomes in each cell is largely switched off early in development.

Variations exist. Some people have one X and no second sex chromosome, or XXY, or other combinations, and a small number have sex chromosomes that don't match the usual pattern for their body.

What happens with an extra or missing chromosome?

Every gene on a numbered chromosome comes in a dose of two, one from each parent. An extra chromosome raises the dose of hundreds or thousands of genes by half at once; a missing one halves them. Most such changes stop an embryo developing, which is a common cause of early miscarriage. A few are compatible with life.

The best-known is Down syndrome, in which a person has three copies of chromosome 21, one of the smallest chromosomes. The U.S. Centers for Disease Control and Prevention says that about 5,775 babies are born with Down syndrome in the United States each year. In about 95% of cases every cell has a full extra chromosome 21 (trisomy 21); in about 3% the extra material is attached to another chromosome (translocation); in about 2% only some cells carry it (mosaic). The chance rises with the mother's age at conception, yet most babies with Down syndrome are born to mothers under 35, because most babies are. People with Down syndrome vary widely in their health and abilities, as everyone does.

The link was found in 1959, when the French researchers Jérôme Lejeune, Marthe Gautier and Raymond Turpin reported an extra small chromosome in children with the syndrome. It came only three years after the human count itself was settled: in December 1955, at Lund University in Sweden, Joe Hin Tjio saw that human cells have 46 chromosomes, not the 48 that textbooks had taught for three decades.

Broken and rejoined chromosomes matter too. The NHGRI notes that one type of leukemia and some other cancers are caused by chromosomes made of joined pieces of broken ones. How chromosomes are shared out evenly in ordinary divisions, and halved for eggs and sperm, is the subject of mitosis vs meiosis, and errors in that sharing are how an extra chromosome usually arises.

Does a bigger chromosome count mean a more complex organism?

No. The number of chromosomes doesn't track complexity, size or intelligence. Wikipedia's list of organisms by chromosome count gives the counts below, for a typical body cell. Some, such as the potato and the fern, carry more than two sets.

Organism	Chromosomes
Jack jumper ant	2 in females (males have 1)
Indian muntjac, a small deer	6 in females, 7 in males
Fruit fly	8
Rice	24
Human	46
Chimpanzee, gorilla	48
Potato	48
Horse	64
Dog, chicken	78
Atlas blue butterfly	about 448 to 452
Adder's-tongue fern	about 1,260

Two close relatives can differ wildly: Reeves's muntjac, another small deer, has 46 chromosomes against the Indian muntjac's 6 or 7, with broadly similar DNA spread across fewer, larger chromosomes. Humans have one pair fewer than chimpanzees and gorillas because human chromosome 2 formed when two ancestral ape chromosomes fused end to end. The evidence includes a leftover pair of telomere sequences in the middle of chromosome 2, as Wikipedia's article on chromosome 2 describes. What matters is the DNA a chromosome carries, not how it is divided up.

Chromosomes are also one of the clearest differences between kinds of cell: bacteria usually keep their DNA in a single circular chromosome, as prokaryotic vs eukaryotic cells shows.

Check yourself

• Without looking back, describe the levels of DNA packing from the double helix to the visible chromosome.
• Why are conditions caused by a variant on the X chromosome more common in males?
• Explain why an extra chromosome changes so much more than a single gene variant usually does.

Sources

• Chromosomes fact sheet — National Human Genome Research Institute
• Nucleosome — National Human Genome Research Institute
• About Down syndrome — U.S. Centers for Disease Control and Prevention
• List of organisms by chromosome count — Wikipedia
• Chromosome 2 — Wikipedia