D3.2 Inheritance

Offspring resemble their parents because they inherit genes from them, and in every eukaryote with a sexual life cycle the route is the same:

1. Body cells of the parents are diploid (2n): they have two sets of chromosomes, so they carry two copies of each autosomal gene, one on each chromosome of a homologous pair.
2. Meiosis halves the chromosome number to make haploid (n) gametes, each with only one copy of each gene (see D2.1 Cell and nuclear division).
3. At fertilization a male and a female gamete fuse to form a zygote, which is diploid again. Every body cell of the new organism is made from it by mitosis, so they all have the zygote’s alleles.

Because both gametes carry the same number of chromosomes, the two parents make an equal contribution to the nuclear genes of their offspring.

Genes, alleles and genotypes

A gene is a heritable factor at a particular locus (position) on a chromosome. Alleles are different versions of the same gene. A diploid organism has two alleles of each autosomal gene, and the combination it has is its genotype.

Separation of the two alleles of a gene into different gametes is called segregation. A heterozygous parent therefore passes on each allele with a probability of ½.

Patterns of inheritance were worked out by crossing plants with different characteristics, as Gregor Mendel did with pea plants (Pisum sativum). In a flowering plant, pollen grains made in the anthers contain the male gametes, and the female gametes are in ovules inside the ovary. Pollination (transfer of pollen to a stigma) is therefore needed before fertilization can happen.

Peas carry anthers and an ovary in the same flower, so they self-pollinate and therefore self-fertilize unless prevented. To cross two chosen plants, the breeder controls which pollen reaches each stigma.

Naming the generations

• P generation: the parents, usually two pure-breeding (homozygous) varieties.
• F1 generation: the offspring of the P cross, grown from the seeds produced.
• F2 generation: offspring of the F1, often obtained by letting F1 plants self-pollinate.

The results of a cross are predicted with a Punnett grid: the possible gametes of one parent go along the top and those of the other down the side, and each box shows one equally likely offspring genotype.

The same technique of controlled cross-pollination is used by plant breeders to combine useful characteristics and so produce new crop varieties (for example higher yield or disease resistance) and new ornamental flower varieties.

The phenotype is the set of observable characteristics of an organism: structural features such as seed shape and functional ones such as an enzyme’s activity. Phenotype depends on the genotype and on the environment.

Dominant and recessive alleles

Mendel crossed pure-breeding round-seeded and wrinkled-seeded peas. All the F1 were round, and when the F1 self-pollinated about 3 round : 1 wrinkled appeared in the F2. The allele for round (smooth) seeds, S, is dominant and the allele for wrinkled seeds, s, is recessive.

Why do SS and Ss plants look the same? The S allele codes for a working starch-branching enzyme; the s allele codes for a non-functional version. A heterozygote has one working allele, which makes enough enzyme for normal starch synthesis, so its phenotype is identical to SS. Only ss seeds lack the enzyme, store more sugar, take up more water and wrinkle as they dry. This is a common reason for recessiveness: the recessive allele codes for a non-functional product and one functional allele is enough.

Phenotypic plasticity

Phenotypic plasticity is the capacity of an organism to develop traits that suit the environment it experiences, by changing patterns of gene expression. The genotype does not change, and many plastic changes are reversible during the organism’s lifetime:

• Tanning: more ultraviolet light on the skin increases expression of genes for melanin synthesis, so skin darkens; it becomes paler when exposure falls.
• Altitude: people who move to high altitude make more red blood cells, which falls again when they return to sea level.

Plasticity is useful where the environment varies over the lifetime of an individual.

Phenylketonuria (PKU) is caused by a recessive allele of an autosomal gene, PAH, that codes for the enzyme phenylalanine hydroxylase. This liver enzyme converts the amino acid phenylalanine into tyrosine.

• People with one or two normal alleles (AA or Aa) make enough working enzyme, so heterozygotes are unaffected carriers.
• People with two PKU alleles (aa) make no working enzyme. Phenylalanine from protein in food builds up in the blood and damages the developing brain, causing intellectual disability if untreated. Less tyrosine is made, and tyrosine is needed for melanin, so untreated patients often have lighter skin and hair.

Most babies are tested for PKU a few days after birth using a heel-prick blood sample. An affected child who follows a diet low in phenylalanine develops normally. PKU is therefore a clear example of a phenotype that depends on genotype and environment together: the aa genotype causes harm only if the diet contains normal amounts of phenylalanine.

Many single-gene disorders in humans are caused by recessive alleles, because the usual mutation destroys the function of a protein and a carrier’s other allele still works.

Single-nucleotide polymorphisms and multiple alleles

New alleles arise by mutation (see D1.3 Mutation and gene editing). Most alleles of a gene differ from each other at only one or a few positions in the base sequence. A position where different bases are found in different members of a species is a single-nucleotide polymorphism (SNP). One gene can contain many SNPs, so the gene pool of a species (all the alleles of all its genes) can contain many alleles of a gene: multiple alleles. Any number of alleles can exist in the population, but a diploid individual has only two.

ABO blood groups

The ABO blood groups are controlled by one gene with three common alleles, written I^A, I^B and i. I^A and I^B code for slightly different enzymes that add different sugars to a glycoprotein on red blood cells, giving the A antigen or the B antigen. The i allele codes for a non-functional enzyme, so neither antigen is added.

Six genotypes give four phenotypes. Parents of groups A and B who are both heterozygous (I^Ai × I^Bi) can have children of all four groups; try this in the Punnett grid generator above.

Codominance and incomplete dominance

Not every pair of alleles shows simple dominance. The difference lies in the phenotype of the heterozygote:

• Codominance: both alleles are fully expressed, so the heterozygote has a dual phenotype. I^AI^B red cells carry both A and B antigens: group AB is not halfway between A and B, it is both.
• Incomplete dominance: the heterozygote has an intermediate phenotype. In the four o’clock flower (Mirabilis jalapa, also called marvel of Peru), red C^RC^R × white C^WC^W gives pink C^RC^W F1 plants, because one C^R allele makes less red pigment than two. Pink × pink gives 1 red : 2 pink : 1 white.

Sex determination in humans

Humans have 22 pairs of autosomes and one pair of sex chromosomes. Females are usually XX, so every egg contains an X. Males are usually XY, so half their sperm carry an X and half a Y. The sex chromosome in the sperm therefore decides the sex of the zygote, and about equal numbers of each are expected.

The Y chromosome carries the SRY gene. Early in development, its product causes the embryonic gonads to develop as testes, which secrete testosterone; this hormone causes male-typical features to develop. In an embryo without a Y, the gonads develop as ovaries and female-typical features develop.

The X chromosome is much larger and carries far more genes than the Y: several hundred, many of them needed by both sexes, against only a few dozen on the Y.

Haemophilia: a sex-linked disorder

A gene on the X chromosome shows sex linkage. Males have only one allele of each X-linked gene (they are hemizygous), so a recessive allele on their X is always expressed. Females have two, so they are affected only if both are recessive and are otherwise carriers.

Haemophilia is caused by a recessive allele of a gene on the X chromosome for a blood-clotting protein (factor VIII in the commonest form). Without it, blood clots slowly and bleeding is prolonged. Alleles are written as superscripts on X: X^H (normal clotting) and X^h (haemophilia).

Haemophilia is much commoner in males, sons inherit it from their mothers, and an affected father cannot pass it to his sons.

A pedigree chart records the phenotypes of members of a family over several generations:

• squares are males and circles are females; affected individuals are shaded
• a horizontal line joins two parents, and a vertical line leads down to their children
• generations are numbered I, II, III… and individuals 1, 2, 3… from left to right

Clues to the pattern of inheritance

Inductive and deductive reasoning

Working with pedigrees uses both kinds of reasoning. Inductive reasoning draws a general conclusion from a limited set of observations: noticing that only males are affected in a family leads to the hypothesis that the condition is X-linked recessive. Deductive reasoning applies a general rule to a particular case: if the condition is X-linked recessive, the unaffected mother of an affected son must be X^HX^h. Inductive conclusions can be wrong, which is why they are tested against further cases.

Marriage between close relatives

Rare recessive alleles are usually hidden in carriers. Close relatives share many alleles inherited from common ancestors, so if they have children together, both parents are much more likely to carry the same recessive allele, and the chance of a homozygous recessive child with a genetic disease rises. This raised risk helps explain why many cultures and legal systems forbid close relatives to marry. Family A in the analyser shows this: the PKU allele reaches both of the cousins’ children from a shared grandparent.

Discrete and continuous variation

• Discrete (discontinuous) variation: individuals fall into a few distinct categories with nothing in between, such as ABO blood group. It is usually controlled by one or a few genes, with little effect of the environment.
• Continuous variation: any value within a range is possible, as for height or skin colour. It results from polygenic inheritance (many genes, each with a small additive effect), from the environment, or from both.

Human skin colour is the classic example. The amount of the pigment melanin in the skin is influenced by alleles of many genes, some increasing and some decreasing melanin, so many different combinations are possible. Exposure to sunlight also increases melanin production. The combined effects give a continuous range from very pale to very dark skin.

For a continuous variable, a frequency distribution is often roughly bell-shaped (normal). Three measures of central tendency summarise it:

• Mean: sum of all values ÷ number of values.
• Median: the middle value when the data are placed in order (the mean of the two middle values if there is an even number). It is less affected by outliers than the mean.
• Mode: the most frequent value or category; the only one that can be used for discrete categories such as blood groups.

Box-and-whisker plots

A box-and-whisker plot shows the spread of continuous data, such as the heights of students in a class, using six features: the minimum, the lower quartile (Q1), the median, the upper quartile (Q3), the maximum and any outliers. The box spans the interquartile range (IQR = Q3 − Q1), which contains the middle half of the data.

Any value lying further than 1.5 × IQR below Q1, or further than 1.5 × IQR above Q3, counts as an outlier.