Principles of Inheritance and Variation

Genetics is the study of how characters (traits) are passed from parents to offspring — the study of inheritance and variation. The foundations were laid by Gregor Mendel, who experimented on the garden pea and is called the "Father of Genetics." He chose the pea because it has clear contrasting traits (such as tall/dwarf, round/wrinkled seeds) and is easy to cross.

A few key terms: a gene is a unit of inheritance; its alternative forms are alleles. An organism is homozygous if its two alleles are the same (TT or tt) and heterozygous if they differ (Tt). The genotype is the genetic make-up; the phenotype is the visible character. An allele that is expressed even in the heterozygous state is dominant; the one that is masked is recessive.

Mendel crossed a pure tall pea (TT) with a pure dwarf pea (tt). In the first generation (F1) all plants were tall (Tt) — this gives Mendel's Law of Dominance (one allele dominates). When the F1 plants were self-crossed, the second generation (F2) showed both tall and dwarf in a ratio of 3 tall : 1 dwarf (phenotypic), and a genotypic ratio of 1 TT : 2 Tt : 1 tt. The reappearance of the dwarf trait shows the Law of Segregation — the two alleles separate during gamete formation, so each gamete carries only one.

Mendel also studied the inheritance of two traits at the same time — a dihybrid cross. For example, he crossed pea plants differing in seed shape and seed colour: round-yellow seeds (RRYY) with wrinkled-green seeds (rryy). Round (R) is dominant over wrinkled (r), and yellow (Y) over green (y).

In the F1, all seeds were round and yellow (RrYy), as expected from dominance. When the F1 was self-crossed, the F2 showed four types of seeds in the ratio 9 round-yellow : 3 round-green : 3 wrinkled-yellow : 1 wrinkled-green — the famous 9:3:3:1 ratio. Notice that new combinations (round-green and wrinkled-yellow) appeared that were not in the parents.

This result gave Mendel's third principle, the Law of Independent Assortment: when two pairs of traits are inherited together, each pair separates and is passed on independently of the other. In other words, the allele a gamete receives for seed shape does not affect which allele it receives for seed colour. This is why new combinations of characters appear in the offspring. (We now know this holds for genes on different chromosomes; genes that are close together on the same chromosome may be inherited together — called linkage.)

Inheritance is not always as simple as Mendel's clear dominant/recessive patterns. Some deviations:

• Incomplete dominance — the heterozygote shows a blend of the two parents. For example, crossing a red-flowered (RR) with a white-flowered (rr) snapdragon gives pink (Rr) flowers; the F2 ratio is 1 red : 2 pink : 1 white.
• Co-dominance — both alleles are fully expressed together, as in human blood group AB, where both A and B antigens appear.
• Multiple alleles — a gene has more than two alleles in the population, as for the ABO blood groups (alleles Iᵃ, Iᴮ, i).

Sex determination in humans is by chromosomes. Humans have 23 pairs of chromosomes; one pair is the sex chromosomes — XX in females and XY in males. All eggs carry an X; sperm carry either X or Y. If an X-sperm fertilises the egg the child is a girl (XX); if a Y-sperm does, the child is a boy (XY). So the father's sperm decides the sex of the child — an important point against blaming the mother.

Some diseases are inherited — genetic disorders. Examples include haemophilia (blood does not clot properly) and colour blindness, both sex-linked (carried on the X chromosome, so they affect males more often); sickle-cell anaemia and thalassaemia (disorders of haemoglobin); and chromosomal disorders such as Down's syndrome (an extra chromosome 21). Understanding these helps in genetic counselling and prevention.

After Mendel, scientists found that genes are carried on chromosomes. The chromosomal theory of inheritance (Sutton and Boveri) states that genes are located on chromosomes and that the behaviour of chromosomes during meiosis (their pairing and separation) exactly parallels the behaviour of Mendel's factors — which is why genes are inherited the way they are.

Genes on the same chromosome tend to be inherited together — this is linkage. However, during meiosis, paired chromosomes can exchange segments by crossing over, which separates linked genes and produces new combinations (recombination). The farther apart two genes are on a chromosome, the more often crossing over occurs between them.

Inheritance can be more complex than one-gene-one-trait. In pleiotropy, a single gene affects several different traits at once (for example, the sickle-cell gene affects the blood and, through it, many organs; phenylketonuria is another example). The human blood groups also show multiple alleles (the ABO system) and the separate Rh factor (Rh-positive or Rh-negative), which is important during pregnancy and blood transfusion.

Sex determination differs among organisms: in humans it is XX (female)/XY (male); in birds the system is reversed — ZZ is male and ZW is female; in honey bees sex depends on the number of chromosome sets (haplodiploidy) — fertilised (diploid) eggs become females, while unfertilised (haploid) eggs become males (drones).

Errors in chromosome number cause chromosomal disorders: Down's syndrome (an extra chromosome 21, trisomy-21), Turner's syndrome (a female with a single X, XO), and Klinefelter's syndrome (a male with an extra X, XXY).