Dominance at the protein level

Mendel’s laws say how alleles are passed on, but not why one allele hides another. The answer comes from what genes do: most code proteins, as Chapter 12 showed, and dominance depends on how much working protein a cell makes.

Wild-type and mutant alleles

For any gene, the allele that is most common in a population is its wild-type allele. A wild-type allele usually codes a protein made in the right amount that works properly. Alleles changed by mutation are mutant alleles, and they tend to be rare.

Many mutations damage a gene so that it makes less of its protein, or a protein that works poorly or not at all. These are loss-of-function alleles, and many of them are recessive.

Why one working copy is often enough

Take pea flower color. The color gene codes an enzyme, protein P, that turns a colorless molecule into purple pigment.

The heterozygote makes only half as much enzyme as the PP plant, but that half still makes enough pigment for fully purple flowers. A PP plant makes far more enzyme than it needs. So P is dominant: one working copy covers for the broken one.

Sometimes a heterozygote does better than 50%. Through gene regulation, the cell can turn up the working allele to make up for the broken one.

Check yourselfIn a plant species, most individuals have hairy leaves, but a rare true-breeding form has smooth leaves. If one gene controls this, which form is more likely homozygous recessive?

The smooth form. Recessive alleles are usually loss-of-function alleles, and losing a function is more likely to remove a feature (the hairs) than to create one.

Many inherited diseases are recessive

The loss-of-function idea explains most human genetic diseases. Thousands of disorders are caused by mutations in single genes, and most of those mutations are recessive: a person is affected only when both copies fail to make an active protein.

Not every recessive allele is harmful. The recessive alleles behind blue eyes and light skin, for instance, cause no disease.

One gene, many effects

When a gene is mutated, the effects often show up in many parts of the body. A single gene affecting several different traits is called pleiotropy, and nearly all genes are pleiotropic to some degree. It happens for three main reasons:

• One protein can affect a cell in more than one way. A faulty microtubule protein, for example, could disrupt both cell division and cell movement.
• A gene can be expressed in several cell types.
• A gene can be expressed at several stages of development.

Cystic fibrosis is a clear case. Its gene codes the transporter that moves chloride ions (Cl⁻) across membranes, and water follows those ions. When the transporter fails, the effects spread:

• Lungs: too little water leaves the cells, so the mucus turns thick and sticky.
• Pancreas: thick mucus blocks the ducts that carry digestive enzymes, so food is poorly absorbed and weight gain is slow.
• Sweat glands: salt can’t be recycled back into the skin, so sweat is unusually salty, which is the basis of a common test for CF.

Check yourselfA single mutant gene causes both skeletal defects and heart defects. What is this called, and give one reason it can happen.

Pleiotropy. It can happen because the gene is expressed in more than one cell type (here, bone and heart cells), or because its protein affects cells in more than one way.