Chapter 6: Genes, Chromosomes & the Genome

The central dogma — DNA is transcribed into RNA, which is translated into protein — is the organizing idea of molecular biology. Before getting into the mechanics of transcription and translation (Chapter 7), it's worth being precise about the vocabulary: chromosome, gene, nucleosome, and genome are related but distinct, and mixing them up is a common source of confusion.

The central dogma, restated

DNA is transcribed into mRNA, which is translated into a chain of amino acids; those amino acids are linked by peptide bonds into a protein. The final product of a gene is therefore always a protein — never a carbohydrate, a lipid, or anything else. DNA also has one more trick: it can copy itself, a process called replication.

This idea was sharpened by Beadle and Tatum's classic one gene–one enzyme hypothesis: a gene is a segment of genetic material that codes for one enzyme. The concept was later broadened to one gene–one polypeptide, since many genes code for proteins that aren't enzymes, or for just one subunit of a larger, multi-subunit protein.

Chromosome structure

A chromosome is an extremely long strand of DNA that carries genetic information in the form of genes. Structurally, it has four landmark regions:

Gene vs. DNA vs. chromosome — these three nest inside each other, smallest to largest: a gene is a segment of DNA that carries genetic information (the gene itself is DNA); DNA is the full-length molecule, of which genes are only certain coding segments; and a chromosome is one long DNA molecule (with its packaging proteins) carrying many genes. Genes are definitely DNA — DNA is not necessarily genes. The analogy the lecture uses: humans are certainly living beings, but living beings are not necessarily human.

Human chromosomes and aneuploidy

Humans have 23 pairs of chromosomes: 22 pairs of autosomes plus one pair of sex chromosomes (XX in females, XY in males) — 46 total. Losing or gaining a chromosome (aneuploidy) is clinically significant:

• Down syndrome — trisomy 21, 47 chromosomes total (an extra copy of chromosome 21).
• Turner syndrome — monosomy X, 45 chromosomes total (only one X chromosome, no Y).

Packaging: the nucleosome

A single human cell's DNA is dramatically longer than the nucleus that has to contain it (more on exactly how much longer below), so it has to be packaged tightly. Picture a long thread that would tangle itself into knots if left loose — DNA solves this the same way, by wrapping around spool-like proteins called histones. One turn of DNA wound around a cluster of eight histone proteins is called a nucleosome; a long chromosome is essentially nucleosomes strung end to end, like beads on a string, which then coil further to fit inside the nucleus.

What is a genome?

A genome is the total amount of genetic information in a specific individual — for humans, the total amount of DNA in the body. Genome size varies enormously across organisms, from roughly 3×10⁷ to 3×10¹¹ base pairs depending on species. The human genome is about 3×10⁹ base pairs.

That translates into a startling compaction fact: the DNA in a single human cell, stretched end to end, is about 2 meters long. An adult body has roughly 10¹⁴ cells, for a total DNA length of about 2×10¹¹ km — compare that to the Earth's circumference (4×10⁴ km) or the Earth–Moon distance (about 384,000 km, roughly 8 times over by that total length). All of that has to fit inside nuclei a few micrometers across, which is exactly the packaging problem nucleosomes solve.

Two types of DNA, and where each is found

• Chromosomal (nuclear) DNA — found in the nucleus of nucleated cells (e.g. white blood cells/leukocytes), associated with hereditary inheritance.
• Mitochondrial DNA (mtDNA) — a separate, much smaller genome inside mitochondria. Human mtDNA is a circular duplex of only 16,569 base pairs, with 2–10 copies per mitochondrion (rising to hundreds in some differentiating embryonic cells). It codes for mitochondrial tRNAs and rRNAs and a handful of mitochondrial proteins — but more than 95% of mitochondrial proteins are actually encoded by nuclear DNA and imported into the mitochondrion.

A comparative quirk: red blood cells

Which has DNA — a human red blood cell, or a bird's? The bird's. Mature mammalian red blood cells lose their nucleus during maturation (freeing up space to carry more oxygen), so they contain no DNA at all — this is exactly why a human DNA test uses white blood cells, not red ones. Bird red blood cells, by contrast, stay nucleated throughout their life and do contain DNA, which is why avian blood samples can be used directly for DNA testing (for example, to determine a bird's sex).

Key teaching point

Keep the hierarchy straight: nucleotide → gene → chromosome → genome, each one built from the level below it. A gene is a functional segment of DNA; a chromosome is one packaged DNA molecule carrying many genes; the genome is the sum of all of an organism's genetic material, split between the (much larger) nuclear/chromosomal genome and the (much smaller, circular) mitochondrial genome. Every fact in this chapter is a consequence of that one nested structure.