Inheritance

Chromosomes, DNA and genes

Inside the nucleus of every cell are chromosomes - thread-like structures made of a chemical called DNA (deoxyribonucleic acid). DNA contains the genetic information that controls what an organism is like, and it carries that information in the form of genes. A gene is a length of DNA that codes for a protein.

The DNA molecule is a double helix: two strands twisted around each other like a spiral ladder. The genetic code is written along the strands in the sequence of bases, and it is that sequence which spells out the instructions for building a protein.

Human body cells are diploid: they contain two sets of chromosomes, one set inherited from each parent. In a diploid cell there is a pair of each type of chromosome, and in a human diploid cell there are 23 pairs, so 46 chromosomes in total. The gametes (sperm and egg cells) are haploid: they contain a single set of chromosomes, just 23. When two gametes fuse at fertilisation the diploid number is restored, so each parent contributes one chromosome of every pair.

• Diploid = two sets of chromosomes (46, in 23 pairs, in humans) - found in body cells.
• Haploid = one set of chromosomes (23 in humans) - found in gametes only.
• A chromosome pair is the two chromosomes that carry the same genes, one inherited from each parent.

From base sequence to protein

A gene codes for a protein, and the order of the bases in the gene decides the order of the amino acids in that protein. The base sequence of a gene determines the sequence of amino acids used to make a specific protein.

The sequence of amino acids is what gives a protein its shape. Different sequences of amino acids give different shapes to protein molecules, and the shape of a protein determines what it can do - so a change in the amino acid sequence can change, or destroy, the protein's function.

DNA controls the cell by controlling which proteins are made. These proteins include enzymes (which catalyse the cell's reactions), membrane carriers (which move substances across membranes) and receptors for neurotransmitters (which let cells respond to signals).

The gene itself stays in the nucleus. A copy of the gene is made as messenger RNA (mRNA) in the nucleus, and the mRNA moves out into the cytoplasm and passes through a ribosome. The ribosome assembles amino acids into a protein molecule, following the sequence of bases in the mRNA.

Almost every cell in an organism contains the same genes, but a cell only makes the proteins it needs. Many genes in a particular cell are therefore not expressed - they are switched off.

Alleles, genotype and phenotype

A gene can exist in more than one form, and each different form is called an allele - an alternative form of a gene. You inherit one allele of each gene from each parent, so a diploid cell carries two alleles of every gene.

An organism's genotype is its genetic make-up - the alleles it carries. Its phenotype is the observable features that result. The phenotype depends on the genotype and, for many features, on the environment as well.

If the two alleles of a gene are identical the organism is homozygous for that gene; if they are different it is heterozygous. Two identical homozygous individuals that breed together are pure-breeding, because all their offspring receive the same allele; a heterozygous individual is not pure-breeding.

A dominant allele is expressed if it is present in the genotype, even if only one copy is there. A recessive allele is only expressed when there is no dominant allele of the gene present - that is, when the organism is homozygous recessive. This is why a recessive characteristic can skip a generation: a heterozygous carrier has a dominant allele that hides it.

Determining sex in humans

Sex in humans is controlled by the sex chromosomes, X and Y. A human female has two X chromosomes (XX) and a human male has one X and one Y (XY). The other 22 pairs of chromosomes are the same in both sexes.

Because a female has two X chromosomes, every egg cell carries an X. A male produces two kinds of sperm: half carry an X and half carry a Y. The sex of a child therefore depends on which sperm fertilises the egg - on the father's gamete, not the mother's.

A genetic diagram shows the cross. All the eggs carry X, while the sperm carry either X or Y. The offspring are XX (female) or XY (male) in a 1 : 1 ratio, so there is roughly a 50 per cent chance of each sex.

A sex-linked characteristic is one in which the gene responsible is located on a sex chromosome, and this makes the characteristic more common in one sex than in the other. The X chromosome carries many more genes than the small Y chromosome, so a recessive allele on the X is more likely to be expressed in males: a male has only one X and so has no second copy to mask it. Red-green colour blindness is an example of sex linkage.

• A sex-linked gene is carried on a sex chromosome, usually the X.
• A male has only one X, so a recessive allele on the X is always expressed - this is why red-green colour blindness is much commoner in males.
• A female needs two copies of the recessive allele to show the characteristic, so she is more often just a carrier.

Monohybrid inheritance and Punnett squares

Inheritance is the transmission of genetic information from generation to generation. A monohybrid cross follows the inheritance of a single gene with two alleles, and Cambridge expects you to set the cross out as a Punnett square.

Work through it in the same order every time: write the genotypes of the two parents; write the allele each parent can put into a gamete (one allele per gamete, because gametes are haploid); write those alleles across the top and down the side of the square; fill in each box by combining the allele from the top with the allele from the side; then count the genotypes and work out the phenotypic ratio.

When two heterozygous parents are crossed (Tt x Tt), the offspring genotypes are 1 TT : 2 Tt : 1 tt. Because TT and Tt both show the dominant feature, the phenotypic ratio is 3 : 1 - three offspring showing the dominant feature to one showing the recessive.

If an organism shows the dominant feature but you do not know whether it is TT or Tt, you can use a test cross: cross it with a homozygous recessive (tt). If any offspring show the recessive feature, the unknown parent must be heterozygous, because it must have passed on a recessive allele. If all the offspring show the dominant feature, the parent is probably homozygous. A cross between a heterozygote and a homozygous recessive (Tt x tt) gives a 1 : 1 ratio of the two phenotypes.

A pedigree diagram shows how a characteristic is inherited through a family, using symbols for males, females and affected individuals. You can use it to work out genotypes and to decide whether an allele is dominant or recessive.

Codominance and the ABO blood groups

Sometimes neither allele is completely dominant. In codominance, both alleles in a heterozygous organism contribute to the phenotype, so both are seen at once. The human ABO blood group system is the classic example.

Blood group is controlled by a single gene that has three alleles - I^A, I^B and I^o - so it is an example of multiple alleles, meaning a gene with more than two forms. I^A and I^B are codominant with each other, and both are dominant to I^o. The four phenotypes are blood group A, blood group B, blood group AB and blood group O.

Because I^A and I^B are codominant, a person with the genotype I^A I^B has both the A and the B antigens on their red blood cells and has blood group AB - neither allele hides the other.

A parent of blood group AB (I^A I^B) and a parent of blood group O (I^o I^o) can have children of blood group A (I^A I^o) or blood group B (I^B I^o), in a 1 : 1 ratio. They cannot have a blood group AB or a blood group O child, because neither parent can pass on both I^A and I^B or two I^o alleles.

Mutation, protein shape and sickle cell anaemia

A mutation is a random change in the base sequence of DNA. Because the base sequence determines the amino acid sequence, a mutation can change the amino acids in a protein, which changes the protein's shape and so its function. A mutation that alters the shape of a protein may stop it working altogether.

Mutations happen at random, and most are neutral - they change the protein but have no effect on the organism. Some are harmful, for example if they stop an enzyme working or change a structural protein so that it cannot do its job. A few are beneficial, giving the organism an advantage that natural selection can act on. Mutations can be increased by ionising radiation, such as X-rays and gamma rays, and by some chemicals called mutagens.

Sickle cell anaemia is caused by a mutation in the gene for haemoglobin. The mutation changes the base sequence, so one amino acid in the haemoglobin molecule is different. This produces an abnormal haemoglobin called HbS, which is less soluble and can crystallise when the oxygen concentration is low. The crystals distort the red blood cell into a sickle shape instead of a smooth disc.

A person who is homozygous (HbS HbS) has sickle cell anaemia. A person who is heterozygous (HbA HbS) is a carrier with sickle cell trait, usually with mild or no symptoms, because the normal allele still makes enough normal haemoglobin. Carriers are healthy but can pass the recessive allele to their children.

In regions where malaria is common, the sickle cell allele is much more frequent than elsewhere. This is because carriers (HbA HbS) have some resistance to malaria - the malarial parasite cannot develop as well inside their red blood cells - so they are more likely to survive and reproduce than people with normal haemoglobin. People who are homozygous for the sickle cell allele often die young, so the harmful allele is balanced against its benefit in carriers. This is a real example of natural selection keeping a harmful allele in a population.

• Sickled cells carry less oxygen, so the person is anaemic and tires easily.
• Sickled cells are stiff and sticky, so they can block small blood vessels, causing severe pain and damaging organs.
• Sickled cells are destroyed faster than normal red blood cells, which makes the anaemia worse.