Where Variation Comes From: Mutations and Genetic Variation

A typo that changed history

About 10 000 years ago, most adults on Earth could not digest lactose, the sugar in milk. Today, many adults in populations with a long history of dairy farming (for example in northern Europe and parts of East Africa) can. The difference comes from small changes in the DNA that switches on the lactase gene, so it stays on in adults. Those changes are mutations.

Natural selection can only choose among differences that already exist. So before we study selection, we need to know where differences come from. This lesson is about genetic variation: the raw material of evolution.

Genes, alleles and the gene pool

You learned in Grade 10 that DNA in the nucleus holds a cell's instructions. A gene is a section of DNA that codes for one product, usually a protein. Proteins do the work of the cell, so they shape traits like fur colour or the ability to digest lactose.

Most genes come in different versions called alleles. One allele might code for a protein that makes dark pigment, another for a protein that makes little pigment. You inherit one allele of each gene from each parent. (You will study how alleles combine in detail in the Genetic Processes unit.)

All the alleles of all the genes in a population make up its gene pool. When biologists say a population evolved, they mean the frequency of alleles in the gene pool changed over generations.

Mutations: changes in the code

DNA is written with four bases: A, T, C and G. A cell reads a gene three bases at a time. Each group of three, called a codon, stands for one amino acid, the building block of proteins.

A mutation is a permanent change in the DNA base sequence. Small point mutations come in three kinds:

• Substitution: one base is swapped for another. Only one codon changes, so at most one amino acid changes. Sometimes the new codon codes for the same amino acid (a silent mutation). Sometimes it codes for a different one. Sometimes it creates a stop signal that cuts the protein short.
• Insertion: an extra base is added.
• Deletion: a base is removed.

Insertions and deletions are usually more damaging. Because the code is read in threes, adding or removing one base shifts the reading frame, so every codon after the mutation is read wrongly. This is a frameshift.

Larger mutations can also change whole chromosomes (pieces deleted, copied or moved). You will meet these in the Genetic Processes unit.

Where do mutations come from?

• Copying errors. DNA is copied before every cell division (you saw this in the S phase of the cell cycle in Grade 10). The copying system is extremely accurate and proofreads itself, but with billions of bases to copy, a few mistakes slip through. Researchers estimate that each person carries several dozen new mutations that neither parent had.
• Mutagens. Ultraviolet (UV) light, X-rays and other high-energy radiation, and certain chemicals (such as some in tobacco smoke) damage DNA and raise the mutation rate.

Only mutations in the germ line (cells that make eggs or sperm) can be passed to offspring and affect evolution. A somatic mutation in a skin cell may cause problems for that person (such as skin cancer) but is not inherited.

Harmful, neutral or beneficial?

Mutations are random: they are not caused by what an organism needs. Most have little or no effect (neutral), especially if they fall in DNA that does not code for anything or are silent. Some are harmful, because they break a protein that works well. A few turn out to be beneficial.

Whether a mutation helps or hurts often depends on the environment. The classic example is the sickle-cell allele of the hemoglobin gene. It comes from a single base substitution that changes one amino acid in hemoglobin, the oxygen-carrying protein in red blood cells.

• People with two copies have sickle-cell disease, a serious illness.
• People with one copy are usually healthy and are more resistant to malaria.

So in regions where malaria is common, such as parts of Africa, one copy is an advantage, and the allele has stayed relatively common. Where there is no malaria, it gives no advantage.

Sources of genetic variation

Mutation is the only source of brand-new alleles, but it is not the only source of variation:

• Sexual reproduction shuffles existing alleles into new combinations every generation. Each egg and sperm gets a different mix of a parent's chromosomes, and fertilization combines two parents. (The details, meiosis and crossing over, are in the Genetic Processes unit.)
• Gene flow brings alleles into a population when individuals migrate in from another population and breed.

These differences, together with the selective pressures of the environment (predators, disease, climate, food supply), are the key factors that drive evolution.

Researching a factor in evolution

Scientists use a research process before they make claims. You will use it in this lesson's activity and throughout the unit.

1. Ask a focused question. Not "What is mutation?" but "How did a mutation help some Tibetan people live at high altitude?"
2. Find sources (A1.3): textbooks, university and government websites, science magazines, peer-reviewed research summaries.
3. Judge each source (A1.9). Who wrote it, and are they an expert? Is it recent? Is it based on evidence? Is it trying to sell something or persuade? Can you confirm the facts in a second source?
4. Take notes in your own words and record each source (author, title, date, website or publisher) so you can cite it.
5. Answer the question with evidence, and say what is still uncertain.