Where genetic variation comes from

DNA, chromosomes, genes and alleles

• DNA is a long double-stranded molecule twisted into a double helix. Each strand is a chain of units made of a sugar, a phosphate and a base, and the four bases pair up across the strands: A with T, and C with G.
• In the nucleus the DNA is wound tightly into chromosomes. Human body cells have 46 chromosomes in 23 pairs; one of each pair came from the mother and one from the father.
• A gene is a section of DNA at a fixed place (its locus) on a chromosome. The order of its bases is the code for one protein, and that protein affects a trait.
• An allele is one version of a gene. Alleles of the same gene differ slightly in their base sequence, so they can code for slightly different proteins.
• Because chromosomes come in pairs, every person carries two alleles for each gene, one on each chromosome of the pair. The two can be the same or different.

Genotype, phenotype, dominant and recessive

• The genotype is the pair of alleles an individual has for a gene, written with letters such as AA, Aa or aa.
• The phenotype is the characteristic that shows: skin colour, blood group, whether someone has a genetic condition.
• A dominant allele shows in the phenotype whenever it is present. A recessive allele only shows when there is no dominant allele, so only in the homozygous recessive genotype.
• Phenotype also depends on the environment. Two people with identical alleles for skin colour can look different after a summer outdoors, but a suntan is not passed on to children.

Mutation: where new alleles come from

• A mutation is a lasting change to the order of bases in DNA. It can happen as a copying error when a cell divides, or be caused by mutagens such as UV light, X-rays and some chemicals.
• A changed base sequence can change the protein, and so the phenotype. Many mutations have no effect, some are harmful, and a few are useful.
• A mutation in a body (somatic) cell, such as a skin cell, affects only the cells that grow from it. It dies with the person and is not inherited.
• A mutation in a cell that makes gametes (eggs or sperm) can end up in a child, and then in every cell of that child. These heritable mutations are the only ones that add new alleles to a population.
• Every allele that exists today began as a mutation in a gamete-making cell, often many generations ago.

Meiosis: making gametes that all differ

• Meiosis is the cell division that makes gametes. One cell with 46 chromosomes divides twice to give four cells with 23 chromosomes each, one from every pair.
• Crossing over: before the first division, the two chromosomes of a pair line up side by side and swap matching sections. Alleles that sat together on one chromosome are recombined into new mixes.
• Independent assortment: the pairs line up in the middle of the cell in a random order, so which chromosome of each pair goes into a gamete is chance. With 23 pairs this alone gives 2 to the power 23, about 8.4 million, possible gametes.
• So the four gametes from meiosis are genetically different from each other and from the parent cell. Meiosis does not make new alleles; it makes new combinations of the alleles a person already has.

Sexual reproduction and random fertilisation

• Fertilisation joins one egg and one sperm, each with 23 chromosomes, into a zygote with 46. The child gets one allele of every gene from each parent.
• Which sperm meets which egg is random, so each parent's millions of possible gametes can pair with any of the other's.
• That is why brothers and sisters (apart from identical twins) all differ, and why two parents who both lack a trait can have a child who shows it.
• The three sources in an individual work together: mutation makes new alleles, meiosis reshuffles them, and fertilisation combines two shuffled sets.

1. gametes from one parent = 2²³ = 8 388 608independent assortment only
2. combinations for a child = 2²³ × 2²³ = 2⁴⁶any egg with any sperm
3. 2⁴⁶ ≈ 70 000 000 000 000about 70 trillion
4. crossing over adds far more, so each child is unique

The nature of variation: helpful, harmful or neutral

• The source of variation is where it comes from; its nature is the effect it has on the individual or population.
• Beneficial: a mutant allele of the CCR5 gene removes the doorway that most strains of HIV use to enter white blood cells, so people with two copies are strongly resistant to those strains.
• Harmful: albinism alleles stop the body making the pigment melanin. In wild animals an albino stands out to predators and prey, and burns or has poor eyesight, so it is less likely to survive and breed.
• Neutral: many differences, such as small changes in DNA between genes, have no effect on survival at all.
• Whether an allele helps can depend on the place: an allele that gives pale fur is harmful in a dark forest but can help on snow.

An identified characteristic: albinism

• The commonest type of albinism, OCA1, is caused by recessive alleles of the TYR gene on chromosome 11.
• The normal allele (A) codes for tyrosinase, the enzyme that starts the making of melanin. A mutant allele (a) has a changed base sequence, so the enzyme it codes for does not work.
• AA and Aa people make melanin and have normal pigment: in Aa, one working allele makes enough enzyme. Only aa people make no working enzyme and have very pale skin and hair, light eyes and weaker eyesight.
• Heterozygous carriers look the same as AA people, so the a allele can be passed down quietly for many generations before two carriers have a child together.