Principles of Inheritance — Notes

Heredity is the transmission of characters from parents to offspring; variation is the degree by which progeny differ from their parents and from each other. Genetics deals with both.

• Gene (Mendel’s factor): the unit of inheritance controlling a character.
• Alleles: alternative forms of a gene (e.g. T for tall and t for dwarf).
• Homologous chromosomes: a pair of chromosomes, one from each parent, carrying the same genes at the same positions (loci).
• Autosomes are chromosomes not concerned with sex determination; sex chromosomes (X and Y in humans) determine sex.
• Genotype: genetic constitution (TT, Tt, tt). Phenotype: observable expression (tall, dwarf).
• Homozygous: two identical alleles (TT or tt); heterozygous: two different alleles (Tt).
• Dominant allele expresses itself in the heterozygote; recessive allele expresses only when homozygous.

Mendel’s work. Gregor Mendel conducted hybridisation experiments on garden peas (Pisum sativum) for seven years (1856–1863) and proposed the laws of inheritance. He selected seven pairs of contrasting characters: stem height (tall/dwarf), flower colour (violet/white), flower position (axial/terminal), pod shape (inflated/constricted), pod colour (green/yellow), seed shape (round/wrinkled) and seed colour (yellow/green).

Reasons for Mendel’s success: pea is easy to grow, has a short life cycle, is naturally self-pollinating (giving true-breeding lines) and is easy to cross-pollinate artificially; he chose clear contrasting characters; studied one or two characters at a time; used large samples and applied statistics; kept careful records; and the characters he chose happened to assort independently.

Monohybrid cross. True-breeding tall (TT) × dwarf (tt) → F1 all tall (Tt). F1 selfed → F2: 3 tall : 1 dwarf (phenotypic ratio) and 1 TT : 2 Tt : 1 tt (genotypic ratio). The Punnett square, devised by Reginald Punnett, shows all possible gamete combinations.

Law of dominance: characters are controlled by discrete units called factors, which occur in pairs; in a dissimilar pair one member (dominant) dominates the other (recessive). It explains the expression of only one parental character in the F1 and both in the F2.

Law of segregation: the alleles do not show any blending, and both characters are recovered as such in the F2; the two alleles of a pair segregate during gamete formation so that each gamete receives only one (law of purity of gametes).

Back cross and test cross. A back cross is a cross of the F1 with either parent. A test cross is a cross of an organism showing the dominant phenotype with the recessive parent to find its genotype: Tt × tt gives 1 dominant : 1 recessive; TT × tt gives all dominant.

Dihybrid cross. Round yellow (RRYY) × wrinkled green (rryy) → F1 all round yellow (RrYy). F1 selfed → F2: 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green. Each gene alone still segregates 3 : 1.

Law of independent assortment: when two pairs of traits are combined in a hybrid, segregation of one pair of characters is independent of the other pair. The F1 forms four kinds of gametes (RY, Ry, rY, ry) in equal frequency, so (3 : 1) × (3 : 1) = 9 : 3 : 3 : 1.

Incomplete dominance. In snapdragon (Antirrhinum, dog flower), true-breeding red (RR) × white (rr) gives pink (Rr) F1. F2: red : pink : white = 1 : 2 : 1, the same as the genotypic ratio. The heterozygote is intermediate because neither allele is completely dominant; the alleles do not blend, since red and white reappear.

Codominance. Both alleles of a heterozygote are fully expressed. ABO blood groups are controlled by gene I with three alleles: Iᴬ, Iᴮ and i. Iᴬ and Iᴮ produce slightly different forms of a sugar polymer on the surface of red blood cells; i produces none. Iᴬ and Iᴮ are completely dominant over i, but when both are present (IᴬIᴮ) both are expressed: codominance, giving group AB.

Multiple alleles. More than two alleles govern the same character in a population (Iᴬ, Iᴮ, i), though any one person carries only two. ABO has six genotypes and four phenotypes: IᴬIᴬ and Iᴬi (A), IᴮIᴮ and Iᴮi (B), IᴬIᴮ (AB), ii (O).

Polygenic inheritance. Traits controlled by three or more genes, each adding a small effect, show continuous variation, and the phenotype also reflects the environment. Human skin colour is controlled by three genes (A, B, C): AABBCC is the darkest, aabbcc the lightest, and AaBbCc an intermediate shade; the number of dominant alleles decides the colour. With k additive genes, the F2 of two heterozygotes shows 2k + 1 classes; for three genes, 7 classes, with 1/64 as dark as AABBCC.

Pleiotropy. A single gene exhibits multiple phenotypic expressions, usually because it affects a metabolic pathway that contributes to several phenotypes.

• Phenylketonuria (PKU) in humans: a single-gene mutation in the gene coding for phenylalanine hydroxylase manifests as mental retardation and reduced hair and skin pigmentation.
• Starch synthesis in pea: gene B. BB plants produce large starch grains and round seeds; bb plants have less efficient starch synthesis, small grains and wrinkled seeds; Bb plants have round seeds but intermediate grain size. So for seed shape B is dominant, but for grain size it shows incomplete dominance — dominance is not an autonomous feature of a gene but depends on the phenotype considered.

Controlled crosses are not possible in humans, so the inheritance of a trait is studied through a family tree, a pedigree, over several generations, using standard symbols: square (male), circle (female), filled symbol (affected), circle with a dot (carrier female), horizontal line (mating), double line (consanguineous mating), vertical line to offspring, and Roman numerals for generations.

Clues to the pattern:

• Autosomal dominant: appears in every generation; every affected person has at least one affected parent; both sexes affected about equally (e.g. myotonic dystrophy).
• Autosomal recessive: may skip generations; affected children can be born to two unaffected (carrier) parents, often in consanguineous marriages; both sexes affected (e.g. sickle-cell anaemia, phenylketonuria).
• X-linked recessive: mostly males affected; passed from carrier mothers to sons; an affected father passes the allele to all his daughters (carriers) but to none of his sons (e.g. haemophilia, colour blindness).

Pedigree analysis is the basis of genetic counselling, predicting the risk of a disorder in future children.

Mendel’s work was rediscovered in 1900 by de Vries, Correns and von Tschermak. Walter Sutton and Theodor Boveri noted that chromosomes behave like Mendel’s factors: they occur in pairs, segregate at meiosis and assort independently. They united chromosome movement with Mendel’s principles as the chromosomal theory of inheritance: genes are located on chromosomes.

Thomas Hunt Morgan tested it with the fruit fly Drosophila melanogaster — easy to grow on simple medium, short life cycle (about two weeks), many progeny from one mating, clear distinction of sexes, and many hereditary variations visible under a low-power microscope.

Linkage. In dihybrid crosses of genes on the X chromosome, Morgan found that the proportion of parental combinations was much higher than non-parental. He attributed this to the physical association of genes on a chromosome (linkage); recombination describes the generation of non-parental combinations, which arises by crossing over between homologous chromosomes during meiosis. Some genes were tightly linked (low recombination, e.g. 1.3 percent) and others loosely linked (higher recombination, e.g. 37.2 percent).

Gene mapping. Alfred Sturtevant, Morgan’s student, used the frequency of recombination between gene pairs on the same chromosome as a measure of the distance between them and mapped their positions on the chromosome.