Pleiotropy and Polygenic Inheritance

Mendel's ratios assume one gene controls one character and one character is controlled by one gene. Two important situations depart from this.

Pleiotropy

Pleiotropy is the ability of a single gene to affect multiple phenotypic characters at once. Examples:

  • Phenylketonuria - the mutant gene affects several traits (raised phenylalanine causing mental retardation, and reduced hair and skin pigmentation).
  • In the garden pea, a single gene for starch synthesis determines both the seed shape (round vs wrinkled) and the size of the starch grains - round seeds have large starch grains, wrinkled seeds small ones.

Polygenic inheritance

A polygenic (quantitative) trait is controlled by three or more genes and shows continuous variation (a range of phenotypes rather than distinct classes). Key features:

  • The effect of each contributing allele is additive - the phenotype reflects the total number of contributing (dominant) alleles, and is also influenced by the environment.
  • Human skin colour (governed by, say, genes A, B, C) is the standard example: AABBCC is the darkest and aabbcc the lightest, with intermediate numbers of contributing alleles giving intermediate shades. Human height is another example.

One-liners: pleiotropy = one gene -> many traits (phenylketonuria; pea starch/seed shape); polygenic = many genes -> one trait, additive effect, continuous variation (skin colour, height).

The Chromosomal Theory of Inheritance

Mendel's work, published in 1865, was rediscovered in 1900 by de Vries, Correns and von Tschermak. By then chromosomes had been seen to move during cell division, and in 1902 Walter Sutton and Theodor Boveri noticed that the behaviour of chromosomes during meiosis exactly parallels the behaviour of Mendel's factors (genes):

  • Both chromosomes and genes occur in pairs.
  • Both segregate at gamete formation, so a gamete receives only one of each pair.
  • Both assort independently of other pairs.

From this parallel, Sutton and Boveri proposed the Chromosomal Theory of Inheritance - that chromosomes are the carriers of the genetic material (genes). Thomas Hunt Morgan and colleagues then experimentally verified this theory using the fruit fly Drosophila melanogaster.

Why Drosophila was ideal

Fruit flies could be grown on simple synthetic medium, complete a life cycle in about two weeks, produce large numbers of progeny, show clear differences between the sexes, and display many types of hereditary variation visible under a low-power microscope.

One-liners: Mendel rediscovered 1900 (de Vries, Correns, Tschermak); Sutton & Boveri (1902) = Chromosomal Theory (chromosomes carry genes; they pair, segregate, assort independently); Morgan verified it using Drosophila.

Linkage and Recombination

Morgan found that when two genes lie on the same chromosome, they tend to be inherited together and do not assort independently. This physical association of genes on a chromosome is linkage.

  • In a dihybrid test cross of linked genes, the parental-type combinations are far more frequent than the non-parental (recombinant) types, so the ratio departs from the expected 1 : 1 : 1 : 1.
  • Recombination is the production of non-parental (new) allele combinations; it arises from crossing over between homologous chromosomes during meiosis.

Strength of linkage and gene mapping

  • Genes that are close together are tightly linked and show low recombination; genes far apart are loosely linked and show higher recombination. Morgan's data on Drosophila showed white-eye and yellow-body genes were tightly linked (low recombination), while white-eye and miniature-wing were loosely linked (higher recombination).
  • Morgan's student Alfred Sturtevant used the frequency of recombination between gene pairs as a measure of the distance between them and used it to map the genes on a chromosome. One map unit (centimorgan) = 1% recombination frequency.

One-liners: linkage = genes on the same chromosome inherited together (violate independent assortment); recombination via crossing over; closer genes -> tighter linkage -> less recombination; Sturtevant mapped genes using recombination frequency; 1 map unit = 1% recombination.