DNA and Genetics

DNA (deoxyribonucleic acid) is a long chain built from repeating units called nucleotides. Each nucleotide has three parts: a phosphate group, a sugar called deoxyribose, and one of four bases: adenine (A), thymine (T), guanine (G) or cytosine (C).

The sugar of one nucleotide bonds to the phosphate of the next, making a sturdy sugar-phosphate backbone. The bases stick out to the side. Two of these chains pair up, base to base, and twist into a double helix, a ladder wound into a spiral.

The pairing follows strict rules: A pairs with T (two hydrogen bonds) and G pairs with C (three hydrogen bonds). A and G are the larger, two-ringed bases (purines); T and C are smaller, one-ringed bases (pyrimidines). Each pair joins one big base to one small one, so every rung is the same width.

The two strands also run in opposite directions, which is called antiparallel. Chemists number the carbons in the sugar, so each strand has a 5′ end ("five prime") and a 3′ end. Where one strand runs 5′ to 3′ going down, its partner runs 5′ to 3′ going up.

Because the pairing rules are fixed, one strand tells you exactly what the other one says. Type a strand of A, T, G and C and check your answer.

Before a cell divides, it has to copy all of its DNA. In a human cell that is about 3 billion base pairs from each parent, roughly 6 billion in all. The copy is semiconservative: the two strands come apart, each one serves as a template, and each new double helix ends up with one old strand and one new strand.

A team of enzymes does the work at a Y-shaped spot called the replication fork.

The 5′ to 3′ rule creates a puzzle. The two template strands are antiparallel, but the fork opens in only one direction. On one template the new leading strand can be built continuously, following the fork. On the other, the lagging strand has to be built backwards in short pieces called Okazaki fragments, each needing its own primer, which ligase later joins together.

The system is very accurate. After proofreading and repair, about one mistake slips through for every billion or so bases copied.

A gene is a stretch of DNA that carries the instructions for one product, usually a protein. People call DNA a recipe, and that is fair as long as you remember the cell doesn't read the whole cookbook at once. It copies out one recipe at a time and takes the copy to the kitchen. That happens in two stages.

There are 4 × 4 × 4 = 64 possible codons. Sixty-one of them stand for amino acids, of which there are only 20, so most amino acids have more than one codon. AUG codes for methionine and is also the usual start signal. UAA, UAG and UGA are stop codons: no tRNA matches them, and the finished chain is released.

The same code is used, with only a few small exceptions, by bacteria, plants, fungi and people. That shared code is one of the strongest pieces of evidence that all life is related.

Type an mRNA sequence (or paste DNA from the coding strand; T will be read as U). The decoder starts at the first AUG and reads codon by codon until it hits a stop. The preset is the start of the human beta-globin gene, part of hemoglobin.

Long before anyone knew about DNA, Gregor Mendel worked out the rules of inheritance by breeding pea plants in a monastery garden in Brno. His key ideas still hold for many traits.

• Each trait is controlled by a gene, and genes come in versions called alleles. You inherit one allele of each gene from each parent.
• A dominant allele (written with a capital letter, like Y) shows up whenever it is present. A recessive allele (y) shows only when there are two copies.
• Your pair of alleles is your genotype (YY, Yy or yy). What you can observe is your phenotype (yellow or green seeds). Two matching alleles is homozygous; two different ones is heterozygous.
• Law of segregation: the two alleles separate when eggs and sperm (or pollen) form, so each gamete carries just one.
• Law of independent assortment: alleles of different genes are sorted into gametes independently, as long as the genes are on different chromosomes or far apart on one.

A Punnett square, devised by the geneticist Reginald Punnett in the early 1900s, lays out every possible combination of gametes from two parents. Each box is equally likely. In Mendel's peas, yellow seeds (Y) are dominant over green (y), and round seeds (R) are dominant over wrinkled (r).

Plenty of traits don't follow these simple rules. In incomplete dominance, a heterozygote is in between (red and white snapdragons give pink). In codominance, both alleles show, as in AB blood type. Height and skin color are polygenic, shaped by many genes plus the environment.

A mutation is any change in a DNA sequence. Many do nothing noticeable, some cause disease, and a few turn out to be useful. Mutations are the raw material that evolution works with.

Point mutations change a single base. When one base is swapped for another (a substitution), there are three possible results:

Try each one in the decoder. The buttons load the beta-globin sequence with a single change, which is outlined.

Not all insertions and deletions cause frameshifts. The most common cystic fibrosis mutation, called F508del, deletes three bases, removing one amino acid (the phenylalanine at position 508) from the CFTR protein but leaving the rest in frame. It still makes the protein fold badly.

Chromosomal mutations affect large pieces of DNA: a chunk can be deleted, duplicated, flipped (inversion), or moved to another chromosome (translocation). Whole chromosomes can also be gained or lost when they fail to separate during meiosis; an extra copy of chromosome 21 causes Down syndrome.

Causes. Many mutations are simply copying errors that slip past proofreading. Others are caused by mutagens: ultraviolet light (which can fuse neighboring T bases), chemicals such as those in tobacco smoke, and ionizing radiation like X-rays. Only mutations in eggs or sperm are passed on to children; mutations in other body cells can lead to cancer but aren't inherited.

For most of history, nobody knew what carried heredity. Many scientists in the early 1900s bet on proteins, which seemed complex enough to hold information. DNA looked too simple. A string of clever experiments changed their minds.