Principles of Inheritance and Variation

In this chapter: Mendel's experiments; monohybrid cross and test cross; laws of dominance and segregation; incomplete dominance; codominance and multiple alleles; dihybrid cross and independent assortment; chromosomal theory; linkage and recombination; polygenic inheritance; pleiotropy; sex determination; mutation; pedigree analysis; Mendelian and chromosomal disorders.

Mendel's experiments

Gregor Mendel worked on the garden pea (Pisum sativum) from 1856 to 1863, using true-breeding lines and large samples, and applying statistics. He studied seven pairs of contrasting traits:

Monohybrid cross

Tall (TT) × dwarf (tt): the F₁ is all tall (Tt). Selfing F₁ gives F₂: phenotypic ratio 3 tall : 1 dwarf; genotypic ratio 1 TT : 2 Tt : 1 tt.

• Law of dominance: characters are controlled by discrete units (factors, now genes) in pairs; when the two differ, one (dominant) expresses over the other (recessive).
• Law of segregation: the two alleles of a pair separate during gamete formation, so each gamete gets only one (the gametes are "pure").
• Test cross: crossing an organism showing the dominant phenotype with the recessive parent to find its genotype. A 1 : 1 ratio means the organism was heterozygous; all dominant means homozygous.

Exceptions to dominance

Incomplete dominance

In snapdragon (Antirrhinum), red (RR) × white (rr) gives pink F₁ (Rr). The F₂ is 1 red : 2 pink : 1 white: the phenotypic and genotypic ratios are the same.

Codominance and multiple alleles

In ABO blood groups, the gene I has three alleles: I^A, I^B and i. I^A and I^B are codominant (both expressed in I^AI^B, giving AB); both are dominant over i. Three alleles give six genotypes and four phenotypes. More than two alleles of a gene in a population is multiple allelism (an individual still carries only two).

Dominance depends on what you look at

In pea seeds, gene B controls starch synthesis. BB makes large starch grains (round seeds); bb makes small grains (wrinkled seeds); Bb seeds are round but have intermediate-size starch grains. For seed shape, round is dominant; for starch grain size, the alleles show incomplete dominance.

Dihybrid cross and independent assortment

Round yellow (RRYY) × wrinkled green (rryy) gives all round yellow F₁ (RrYy). The F₂ gives 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green.

Law of independent assortment: when two pairs of traits are combined in a hybrid, the segregation of one pair is independent of the other.

Note: 9:3:3:1 is the phenotypic ratio; the genotypic ratio of a dihybrid F₂ is 1:2:1:2:4:2:1:2:1 (nine genotypes).

Chromosomal theory, linkage and recombination

• Walter Sutton and Theodore Boveri (1902) linked Mendel's factors to chromosome behaviour during meiosis: the chromosomal theory of inheritance.
• Thomas Hunt Morgan worked on the fruit fly Drosophila melanogaster (short life cycle, many offspring, easily distinguished male and female, many visible variations). In dihybrid crosses with X-linked genes, he found the genes did not assort independently.
• Linkage: physical association of genes on a chromosome. Recombination: generation of non-parental gene combinations (by crossing over).
• Genes for yellow body and white eye were very tightly linked (only 1.3% recombination); white eye and miniature wing showed 37.2% recombination. Tightly linked genes show low recombination.
• Alfred Sturtevant used recombination frequency as a measure of the distance between genes, and made the first genetic maps.

Polygenic inheritance and pleiotropy

• Polygenic traits are controlled by three or more genes, each contributing additively, and are influenced by environment. Examples: human skin colour and height. The phenotype shows a continuous range.
• Pleiotropy: one gene affects multiple phenotypic traits. Example: phenylketonuria, a single-gene mutation causing mental retardation and reduced hair and skin pigmentation.

Sex determination

Henking (1891) saw a specific nuclear structure in 50% of the sperms of an insect during spermatogenesis and called it the X body; it was later named the X chromosome.

Male honey bees produce sperms by mitosis. A drone has no father and cannot have sons, but has a grandfather and can have grandsons.

Mutation

• An alteration in DNA sequence, changing genotype and phenotype.
• Chromosomal aberrations (deletions, duplications) are common in cancer cells.
• A point mutation is a change in a single base pair, e.g. sickle-cell anaemia.
• Insertion or deletion of base pairs causes frame-shift mutations.
• Agents that cause mutation are mutagens, e.g. UV radiation.

Mendelian disorders

These are studied through pedigree analysis (family charts).

Thalassaemia vs sickle-cell: thalassaemia is a quantitative problem (too few globin molecules); sickle-cell anaemia is a qualitative problem (incorrectly functioning globin).

Chromosomal disorders

• Aneuploidy: gain or loss of chromosomes due to failure of chromatid segregation (trisomy, monosomy). Polyploidy: an increase in whole sets of chromosomes due to failure of cytokinesis after telophase; common in plants.

Common traps: (1) Incomplete dominance: same phenotypic and genotypic F₂ ratio (1:2:1). (2) Birds: the female is heterogametic (ZW). (3) Sickle-cell: GAG to GUG, Glu to Val at position 6 of β-chain. (4) α-globin genes on chromosome 16, β on 11. (5) Klinefelter's = XXY (male); Turner's = XO (female).

NEET focus

• Mendel's seven traits; monohybrid and dihybrid ratios; test cross.
• Snapdragon (incomplete dominance); ABO (codominance, multiple alleles).
• Morgan's recombination values; Sturtevant's maps.
• Sex determination systems, especially honey bee.
• Mendelian disorders: inheritance pattern and molecular basis; chromosomal disorders with karyotypes.

Practice questions