1The idea in one paragraph

Each parent makes gametes by meiosis, and each gamete carries one copy of every chromosome, so one version of every gene. Fertilisation joins two gametes, so the child has two versions of each gene, one from each parent. Those versions are alleles. What the child looks like, its phenotype, depends on which two alleles it holds and on the environment it grows up in. Sometimes one allele hides the other (dominance), sometimes both show (codominance), sometimes the result is a blend (incomplete dominance). Genes on the X chromosome follow a different pattern in males and females. Many traits are controlled by several genes at once and vary continuously. At HL you follow two genes at a time, see how their position on the chromosomes changes the result, and test the result with statistics.

2Gametes, zygotes and two copies of every gene

Every eukaryote that reproduces sexually runs the same cycle. Body cells are diploid (2n): they have two sets of chromosomes, one inherited from each parent. Meiosis makes haploid (n) gametes with one set. Two haploid gametes fuse at fertilisation and form a diploid zygote. The cycle then repeats in the next generation. Figure 1 follows one gene round it.

The consequence for genes is simple and it drives everything else in this page. Each autosome (any chromosome other than the sex chromosomes) comes in a matching pair, so a diploid cell holds two copies of each autosomal gene. The two copies sit at the same position, the same locus, on the two homologous chromosomes. They may be identical, or they may differ slightly in base sequence. Each gamete receives only one of the two, chosen by which chromosome of the pair goes into it at meiosis.

Meiosis halves: one allele of each gene goes into each gamete. Fertilisation doubles: two alleles of each gene come together in the zygote.

3Genes, alleles, genotype and phenotype

Four words, and the marks depend on keeping them apart.

• A gene is a length of DNA at a particular locus that codes for a polypeptide (or an RNA). The gene for flower colour in a pea is one gene.
• An allele is one version of a gene, differing from other versions in its base sequence, often by only one or a few bases. The purple and the white version are two alleles of the same gene.
• The genotype is the combination of alleles an organism has inherited for a gene, written with letters: PP, Pp or pp.
• The phenotype is the observable trait: purple flowers, blood group A, a height of 170 cm.

If the two alleles are the same (PP or pp) the organism is homozygous for that gene. If they differ (Pp) it is heterozygous.

Why a heterozygote can look exactly like a homozygote. A dominant allele has its effect whether one copy or two copies are present. A recessive allele shows only when there is no dominant allele, so only in the homozygous recessive genotype. The reason is usually molecular. The dominant allele codes for a working protein, often an enzyme. The recessive allele codes for a protein that does not work, or for no protein at all. One working copy makes enough enzyme to produce the normal phenotype, so PP and Pp look the same: both make the purple pigment. Only pp, with no working copy, makes no pigment and has white flowers. Write it in an answer as: one functional allele is enough to produce sufficient protein.

Phenotype is genotype plus environment. The guide expects you to suggest examples of three kinds.

4Phenotypic plasticity

Phenotypic plasticity is the capacity of an organism to develop traits suited to the environment it experiences, by changing which genes are expressed and how strongly. The genotype does not change. The same alleles are there; the environment switches some of them on or up, others off or down. Because it is a matter of expression, the change can often be reversed within the individual's lifetime.

• Tanning. Ultraviolet light increases the expression of melanin-producing genes in skin cells, and the darker skin protects deeper cells. Out of the sun, the tan fades.
• Living at altitude. Low oxygen raises the rate of red blood cell production, so the blood carries more haemoglobin. At sea level the count falls back.
• Water crowfoot. This aquatic buttercup grows thread-like leaves under water and broad, flat leaves on the surface, on the same plant, from the same genes.

The exam trap is to call these mutations or adaptations inherited by the next generation. They are neither. The child of a tanned parent is born with the same skin as the child of an untanned one.

5How a cross is done in a flowering plant

In a flowering plant the male gametes are inside pollen grains, made in the anthers, and the female gametes are inside ovules, in the ovary. So a cross needs pollination: pollen from one plant has to reach the stigma of the other. Many plants, such as peas, carry both anthers and ovaries in the same flower, and pea flowers normally stay closed, so they pollinate themselves. That is self-pollination and leads to self-fertilisation. It is useful, because a line bred by self-fertilisation for generations becomes homozygous, or pure-breeding. It is also a problem, because a cross between two chosen plants must stop self-pollination first. Figure 2 sets out the method.

The two chosen parents are the P generation. Removing the anthers from the seed parent stops it fertilising itself; the bag keeps out stray pollen. The seeds grow into the F1 generation (first filial), and the offspring of F1 plants selfed or crossed with each other are the F2 generation.

A Punnett grid predicts the result: the gametes of one parent along the top, the gametes of the other down the side, and each box is one possible zygote. Figure 3 follows tall and dwarf pea plants, where the tall allele T is dominant over the dwarf allele t.

Every F1 plant is Tt and tall. The F2 has the genotypes TT, Tt and tt in the ratio 1 : 2 : 1, so the phenotypes are tall and dwarf in the ratio 3 : 1. Suppose a grower counts 306 tall and 106 dwarf F2 plants. That is 306 ÷ 106 ≈ 2.9 : 1, close to 3 : 1. A ratio from real counts is never exact, because fertilisation is random; section 15 shows how to test whether a gap is too big to be chance.

A ratio is a probability, not a promise. "3 : 1" means each F2 seed has a 1 in 4 chance of being dwarf. In a family of four children, all four can be affected, or none.

Crosses like this are how plant breeders produce new varieties of crops and garden flowers: they cross two plants with useful traits, select the offspring that combine them, and self those until the new line breeds true.

6Phenylketonuria: a disease due to a recessive allele

Phenylketonuria (PKU) is a recessive genetic condition. The gene involved is autosomal and codes for the enzyme phenylalanine hydroxylase, which converts the amino acid phenylalanine into another amino acid, tyrosine. The mutant allele codes for an enzyme that does not work.

Use A for the normal allele and a for the PKU allele.

• AA: two working copies. No PKU.
• Aa: one working copy makes enough enzyme. No PKU. This person is a carrier.
• aa: no working enzyme. Phenylalanine from the diet builds up in the blood, and at high concentration it damages the developing brain.

Two carriers have a 1 in 4 chance, each time, of a child with PKU:

PKU is also the clearest example of genotype and environment acting together. Newborn babies in many countries have a heel-prick blood test for it. A child with genotype aa who is fed a diet very low in phenylalanine grows up with normal brain development. The genotype is the same; the environment, the diet, changes the phenotype.

7Gene pools, SNPs, multiple alleles, and dominance that is not complete

A single-nucleotide polymorphism (SNP) is a position in the genome where the base varies between individuals of a species: some people have A, others G, at the same place. A SNP inside a gene gives two different alleles of that gene. A gene may contain many SNPs, and each combination is a different allele, so a species can hold many alleles of one gene in its gene pool, all the alleles of all the genes in a population. Keep one limit in mind: however many alleles exist in the gene pool, one diploid individual inherits only two of them, one from each parent, and they may be the same.

ABO blood groups: multiple alleles. The ABO gene has three common alleles. The guide's symbols are Iᴬ, Iᴮ and i. Iᴬ and Iᴮ code for enzymes that add different sugars to a glycoprotein on the surface of red blood cells, making the A antigen or the B antigen. The i allele codes for an enzyme that does not work, so neither antigen is made.

Six genotypes, four phenotypes.

Codominance and incomplete dominance both describe a heterozygote that does not look like either homozygote, but in different ways. Figure 4 puts them side by side.

• In codominance, the heterozygote has a dual phenotype: both alleles are fully expressed and both effects show. An IᴬIᴮ person has A antigens and B antigens on every red blood cell.
• In incomplete dominance, the heterozygote has an intermediate phenotype. In the four o'clock flower (Mirabilis jalapa, also called marvel of Peru), a plant with two red-flower alleles (CᴿCᴿ) has red flowers, CᵂCᵂ has white flowers, and CᴿCᵂ has pink flowers: one working allele makes only about half as much red pigment. Cross two pink plants and the F2 is 1 red : 2 pink : 1 white. Here, unlike Figure 3, the phenotype ratio equals the genotype ratio, because every genotype looks different.

Notice the notation: both alleles take the same base letter with different superscripts, because neither is dominant.

8Sex determination and sex-linked genes

Humans have 22 pairs of autosomes and one pair of sex chromosomes. Females are XX and males XY. Every egg carries one X. Half the sperm carry an X and half a Y, so the sperm decides: an X sperm gives an XX zygote, a Y sperm an XY zygote, in equal numbers on average. A gene on the Y chromosome (called SRY) switches on the development of testes in the embryo, and the hormones the testes release then produce male-typical physical characteristics. Without it, female-typical characteristics develop.

The X and Y are very different in size. The X carries several hundred genes; the Y carries only a few dozen, mostly concerned with male development and sperm production. So most genes on the X have no partner on the Y. A male has only one copy of each of those genes, and whatever allele it is, it shows. That is sex linkage: a pattern of inheritance that differs between the sexes because the gene is on a sex chromosome.

Haemophilia is the guide's example. Blood clotting needs a cascade of proteins, and one of them, factor VIII, is coded by a gene on the X chromosome. A recessive allele codes for a faulty factor VIII, and blood does not clot properly, so small injuries bleed for a long time. It is treated by injections of the missing factor.

Write the alleles as superscripts on the X, as the guide requires: Xᴴ is the normal allele, Xʰ the haemophilia allele. The Y is written as plain Y, with no allele, because the gene is not on it.

Figure 5 crosses a carrier woman with a man who does not have haemophilia.

Each son has a 1 in 2 chance of haemophilia. Each daughter has a 1 in 2 chance of being a carrier and no chance of being affected, because she receives her father's Xᴴ. Three rules follow, and they are the answers to most sex-linkage questions.

1. A male with haemophilia got his Xʰ from his mother: his father gave him a Y.
2. An affected father passes his Xʰ to every daughter, who are all carriers at least, and to no son.
3. Haemophilia is far commoner in males because one recessive allele is enough in a male, while a female needs two, one from each parent.

9Pedigree charts

A pedigree chart is a family tree that records who shows a trait. Squares are males and circles are females. A horizontal line between a square and a circle is a mating; a vertical line down from it leads to the children, shown in birth order from left to right. A filled symbol means the person is affected. Figure 6 is an invented family with a rare disorder.

Work through it the way a Paper 2 question wants.

Is the allele dominant or recessive? Look for two unaffected parents with an affected child. Individuals II-3 and II-4 are unaffected, yet their daughter III-2 is affected. She must have inherited the allele from them, so they carry it without showing it. The allele is recessive.

Is it autosomal or sex-linked? For an X-linked recessive, an affected daughter needs an Xʰ from her father, so her father would be affected. III-2's father, II-3, is unaffected. So the allele is not X-linked: it is autosomal recessive.

Genotypes. Call the alleles D and d. III-2 is dd. Both her parents are therefore Dd. The chart agrees: II-3's father, I-1, is affected (dd), so II-3 must have received a d from him. Her unaffected brother III-1 is DD or Dd, and from the chart alone you cannot say which. Write "DD or Dd" and give the reason; a single guessed genotype loses the mark.

Nature of science: inductive and deductive reasoning. Inductive reasoning moves from particular observations to a general conclusion: from several families in which unaffected parents have affected children, a geneticist concludes that the condition is recessive. The conclusion goes beyond the evidence, so it could be overturned by a new case. Deductive reasoning moves from a general rule to a particular conclusion that must follow: if the allele is autosomal recessive, then III-2 is dd, and therefore each parent is Dd. On a pedigree you use both, in that order: induce the pattern from part of the chart, then deduce individual genotypes from the pattern.

Why many societies prohibit marriage between close relatives. Most harmful alleles are recessive and rare, so an unrelated couple seldom both carry the same one. Close relatives inherited many of their alleles from the same recent ancestors. First cousins, for example, share on average one eighth of their genes by that route. If one carries a rare recessive allele, the other is much more likely to carry it too, and their children have a much higher chance of being homozygous recessive and affected. The rule long predates genetics, but genetics explains why it reduces harm.

10Continuous variation, and how to display it

Blood group is a discrete variable: each person falls into one of four categories, and there is nothing in between. Height, mass and skin colour are continuous variables: they can take any value within a range, and a large sample produces a smooth, usually bell-shaped distribution.

Two things produce continuous variation.

Polygenic inheritance. The trait is controlled by several genes, each with a small additive effect. Imagine skin colour controlled by three genes, each with an allele that adds pigment and one that does not. A person can carry anything from zero to six pigment-adding alleles, giving seven classes. In a cross between two people who are heterozygous for all three genes, the middle classes are far more likely than the extremes, because there are many more ways to get three pigment-adding alleles than to get six. Figure 7 shows the prediction.

Real human skin colour involves more genes than this, and then environment smooths the steps away: sun exposure increases melanin production (section 4), so people with the same genotype differ in shade. More genes plus environment gives a continuous curve.

Summarising a continuous variable. The mean is the sum of the values divided by their number. The median is the middle value when they are in order. The mode is the most frequent value. Take these twenty invented heights of sixteen-year-olds, in centimetres, already in order:

152, 158, 161, 163, 164, 166, 167, 168, 170, 170, 170, 172, 173, 174, 175, 177, 178, 180, 183, 199

The mean sits above the median because of the one very tall student. That is a clue that the data contain an outlier.

Box-and-whisker plots. A box-and-whisker plot shows six things: the minimum, the first quartile (Q1), the median, the third quartile (Q3), the maximum, and any outliers. The quartiles are the medians of the lower and upper halves of the data. The interquartile range (IQR) is Q3 − Q1, the spread of the middle half. A value is an outlier if it lies more than 1.5 × IQR above Q3 or below Q1.

Figure 8 draws the result. The whisker stops at the largest value that is not an outlier (183 cm), and the outlier is plotted on its own as a point.

16Linking questions

What are the principles of effective sampling in biological research? A sample must be random and large enough for chance deviations to average out: an F2 of 20 plants can miss a 1-in-16 class altogether, an F2 of 500 will not.

What biological processes involve doubling and halving? Meiosis halves the chromosome number and fertilisation doubles it (Figure 1); DNA replication doubles the DNA before either division.