Genetics & Inheritance

Homozygous and heterozygous

The two alleles you carry for a given gene can be the same or different:

• Homozygous: both alleles are the same (e.g. BB or bb)
• Heterozygous: the two alleles are different (e.g. Bb)

If you are heterozygous and one allele is dominant, the dominant version is the one you show in your phenotype. The recessive allele is still there in your genotype, but it is masked by the dominant one.

An example: the PTC tasting gene. Some people can taste a bitter chemical called phenylthiocarbamide (PTC, found naturally in some vegetables like sprouts); others can't taste it at all. The ability to taste PTC is controlled by one gene with two alleles:

• T = can taste PTC (dominant)
• t = cannot taste PTC (recessive)

Note that two different genotypes (TT and Tt) produce the same phenotype (taster). The only way to be a non-taster is to have two copies of the recessive allele.

Other terms you should know

• Genome: the whole of an organism's DNA, taken together. Every chromosome, every gene, every base. Sequencing the entire human genome was completed in 2003.
• Diploid: a cell with two complete sets of chromosomes (e.g. a human body cell with 23 pairs = 46 chromosomes). Written as 2n.
• Haploid: a cell with one complete set of chromosomes (e.g. a human sperm or egg with 23 chromosomes). Written as n.
• Variation: differences between individuals of the same species. Variation can be genetic (caused by different alleles), environmental (caused by lifestyle, diet, accidents), or a mix of both.

2. DNA structure

DNA (deoxyribonucleic acid) is the molecule that stores all the genetic information in every living cell. Its structure was worked out in 1953 by Watson, Crick, Franklin and Wilkins.

The double helix

DNA is built as a double helix: two long strands wound around each other in a regular spiral, like a twisted ladder. Each strand is made of a chain of smaller units called nucleotides.

A nucleotide has three parts:

• A phosphate group (forms part of the strand backbone)
• A deoxyribose sugar (also part of the backbone)
• A nitrogenous base (the variable part)

The phosphates and sugars alternate along the outside of each strand, forming the sugar-phosphate backbone. The bases stick inwards from the strands and form the rungs of the ladder.

The four bases and how they pair

DNA has only four different bases:

• A (adenine)
• T (thymine)
• G (guanine)
• C (cytosine)

On the two strands of the helix, the bases pair up across the middle of the ladder by following strict complementary base-pairing rules:

• A always pairs with T
• G always pairs with C

This means that if you know the order of bases on one strand, you can work out the order on the other. For example, if one strand reads A-T-G-C-A, the partner strand must read T-A-C-G-T.

The two strands are held together by hydrogen bonds between the paired bases. These are weak enough to be broken easily (so the strands can separate during DNA replication and protein synthesis) but strong enough in total to keep the helix stable.

Genes are sections of DNA

A gene is just a length of DNA that codes for one specific protein. A typical human chromosome contains thousands of genes, each separated from the others by non-coding regions.

The sequence of bases in a gene determines the sequence of amino acids in the protein it codes for. The genetic code works in groups of three bases: every group of three bases (a triplet) codes for one specific amino acid.

3. RNA structure

RNA (ribonucleic acid) is the messenger molecule that carries the instructions in a gene from the nucleus to the place where proteins are made. RNA is similar to DNA but with three important differences:

In RNA, uracil (U) plays the role that thymine (T) plays in DNA, so the new pairing rules are:

• A pairs with U (in RNA-DNA pairing)
• G pairs with C

There are several different types of RNA. The two most important for protein synthesis are:

• Messenger RNA (mRNA): a copy of a single gene that carries the code from the nucleus to a ribosome
• Transfer RNA (tRNA): brings the right amino acids to the ribosome in the right order

4. Protein synthesis: from gene to protein

The process of using a gene to build a protein has two main stages:

1. Transcription: the DNA code of the gene is copied into an mRNA molecule, inside the nucleus.
2. Translation: the mRNA molecule is read by a ribosome, which uses the code to build the corresponding chain of amino acids in the cytoplasm.

Transcription (in the nucleus)

1. The relevant section of DNA unwinds as hydrogen bonds between the complementary bases break.
2. One strand of the gene acts as the template strand.
3. Free RNA nucleotides in the nucleus line up against the template strand according to the complementary base-pairing rules (A pairs with U, T pairs with A, G pairs with C, C pairs with G).
4. The RNA nucleotides are joined together into a single-stranded mRNA molecule.
5. The mRNA detaches from the DNA, which rewinds back into a double helix.
6. The mRNA molecule leaves the nucleus through a pore in the nuclear envelope.

So transcription produces an mRNA copy of the gene that can travel out of the nucleus to the protein-building machinery.

Translation (in the cytoplasm)

1. The mRNA molecule arrives at a ribosome in the cytoplasm.
2. The ribosome reads the mRNA three bases at a time. Each group of three bases is a codon and codes for one specific amino acid.
3. In the cytoplasm, many free tRNA molecules are floating around. Each tRNA carries a specific amino acid at one end and has a triplet of bases (anticodon) at the other end.
4. A tRNA whose anticodon matches the first codon on the mRNA binds to it. Then a second tRNA binds to the next codon. The two amino acids carried by these tRNAs are joined together by a peptide bond.
5. The ribosome moves along the mRNA one codon at a time. Each time, a new tRNA brings the matching amino acid, which is added to the growing chain.
6. When the ribosome reaches a stop codon, translation stops. The completed chain of amino acids is released.
7. The chain folds up into the specific 3D shape of the finished protein, which can now do its job (e.g. as an enzyme, antibody or structural protein).

The big picture

Gene (DNA) → mRNA (transcription, in the nucleus) → Protein (translation, on the ribosome)

The sequence of bases in DNA → determines the sequence of bases in mRNA → determines the sequence of amino acids in the protein → determines the shape and function of the protein → determines the characteristic of the organism.

5. Monohybrid inheritance and Punnett squares

A monohybrid cross is a cross between two individuals looking at one gene with two alleles. The standard tool for predicting the outcome of a monohybrid cross is a Punnett square.

How to set up a Punnett square

1. Identify the parent genotypes. Use a clear letter for the gene, with the capital for the dominant allele and the lowercase for the recessive (e.g. T and t, or B and b; avoid letters like C/c and S/s where the case is hard to tell apart in handwriting).
2. Split each parent's alleles into the two gametes they can produce.
3. Draw a 2×2 grid. Put one parent's possible gametes along the top, the other parent's possible gametes down the side.
4. Fill in the four boxes of the grid by combining the alleles at the top and side of each box. These are the possible offspring genotypes.
5. Work out the phenotype for each genotype using the dominant/recessive rules.
6. State the ratio of phenotypes.

From ratio to probability

Each new offspring is an independent event. The ratio from a Punnett square tells you the probability of each outcome for any single offspring.

For example, with Tt × Tt:

• Probability of a tall offspring = 3/4 = 0.75 = 75%
• Probability of a short offspring = 1/4 = 0.25 = 25%

If the parents have four offspring, the ratio will not always come out exactly 3:1. You might get 4 tall and 0 short, or 2 tall and 2 short. The 3:1 ratio only emerges accurately over many offspring. This is why pea plants are useful for these experiments, because a single plant can produce hundreds of seeds.

6. Codominance: when both alleles show

In most monohybrid crosses, one allele is dominant and the other is recessive. But sometimes both alleles in a heterozygote show their effects in the phenotype. This is called codominance.

The ABO blood group system

The classic example is the inheritance of human blood groups. The ABO gene has three alleles (not two):

The rules of dominance are:

• I^A and I^B are codominant with each other. If you have one of each, both antigens appear on your red blood cells.
• Both I^A and I^B are dominant over I^O.

This gives four possible phenotypes (blood groups A, B, AB, O) from six possible genotypes:

7. Sex chromosomes and sex determination

The 23rd pair of human chromosomes is the sex chromosomes. The other 22 pairs are called autosomes and are the same in males and females.

• Females have two X chromosomes (XX)
• Males have one X and one Y chromosome (XY)

The X chromosome is much larger than the Y and carries many more genes. The Y chromosome is short and carries relatively few genes, but it does contain the SRY gene that triggers the development of male reproductive organs in an embryo.

How sex is inherited

When gametes are made:

• A mother's eggs all carry an X chromosome (she has no Y to pass on).
• A father's sperm carry either an X or a Y, in a 50:50 mix.

So the father determines the sex of the child:

• If an X-carrying sperm fertilises the egg → XX → female
• If a Y-carrying sperm fertilises the egg → XY → male

Punnett square for inheritance of sex:

The ratio is 1 male : 1 female, so each new child has a 50% chance of being male and a 50% chance of being female.

8. Family pedigrees

A family pedigree is a diagram that traces how a particular characteristic (often a genetic disorder) passes through several generations of a family. Pedigree diagrams are useful for working out:

• Whether the characteristic is dominant or recessive
• The probability that a particular family member is affected, or could pass the condition on to their children

Pedigree symbols

Pedigree diagrams use standard symbols:

• Squares represent males; circles represent females
• Filled-in (shaded) shapes represent affected individuals (those showing the characteristic)
• Empty shapes represent unaffected individuals
• A horizontal line between a male and a female means they are a couple who have produced children
• A vertical line going down from a couple connects them to their children, who are shown side by side

Reading a pedigree

To work out whether a trait is dominant or recessive:

• If two unaffected parents have affected children, the trait must be recessive (because both parents are carriers but don't show the trait).
• If every affected child has at least one affected parent, the trait is likely to be dominant.

9. Mutations

A mutation is a rare, random change in the sequence of bases in a DNA molecule. Mutations happen continuously in every living cell, mostly without consequence.

Three types of mutation

There are three main ways the DNA sequence can change:

Most mutations don't matter

The vast majority of mutations have no effect on the organism. They can be neutral for several reasons:

• The mutation happens in a non-coding region of DNA (the bit between genes).
• The new codon still codes for the same amino acid (the genetic code has redundancy: many amino acids are coded for by several different codons).
• The new amino acid is so similar to the original that the protein's shape and function are unaffected.

When mutations do matter

Occasionally a mutation produces a real change in the protein, with consequences:

• Harmful mutations produce a protein that does not work properly. Many genetic diseases are caused by mutations of this kind. Examples:
  • Sickle cell anaemia: a single base substitution in the gene for haemoglobin changes one amino acid. The mutant haemoglobin sticks together in the wrong shape, deforming red blood cells into sickle shapes that block small blood vessels.
  • Cystic fibrosis: a mutation in a gene called CFTR produces a faulty membrane protein. This causes thick sticky mucus to build up in the lungs and digestive system.
  • Huntington's disease: an extra repetition of three bases in a gene called HTT produces a protein that damages brain cells in middle age.
• Beneficial mutations produce a protein that works better, or gives a new function. If the new variant helps the organism survive or reproduce, it can spread through the population by natural selection (covered in topic 14).
• Cancer is caused by mutations in the genes that normally control cell division. The mutated cells divide uncontrollably, forming a tumour.

What causes mutations

Mutations happen spontaneously during DNA replication, even with no external cause. Cells have repair mechanisms to fix most mistakes, but a few slip through.

Several external factors increase the rate of mutation:

• Ionising radiation: gamma rays, X-rays, ultraviolet (UV) rays. Energy from the radiation breaks bonds in DNA molecules.
• Chemical mutagens: certain chemicals damage DNA directly. Examples include the tar in tobacco smoke, some pesticides, and a small number of industrial chemicals.
• Some viruses can insert their own DNA into the host's chromosome, disrupting genes.

People exposed to large doses of these factors over time have a higher risk of developing cancer. This is why skin protection from UV, avoiding smoking, and minimising exposure to radiation all reduce cancer risk.

10. Sources of variation: mitosis vs meiosis, and random fertilisation

Variation between individuals comes from two main sources: genes and environment. Most genetic variation in sexually-reproducing species comes from three particular events.

Mitosis vs meiosis

The body uses two completely different kinds of cell division:

How meiosis generates variation

Meiosis produces gametes that each carry only half the chromosomes (just one of each homologous pair). Critically, which chromosome from each pair ends up in which gamete is random. With 23 pairs of chromosomes, that's 2^23 ≈ 8 million different combinations of chromosomes per gamete, so a single person can produce a huge number of genetically different gametes.

Random fertilisation

When a sperm and an egg meet at fertilisation, the choice of which sperm fertilises which egg is also random. Combined with the meiosis-generated variation between gametes, this means that every zygote (and so every offspring) has a unique genetic combination.

This is why brothers and sisters from the same parents are different from one another (except for identical twins, who develop from a single zygote that has split, and so share the same genes).

11. Genetic vs environmental variation

Differences between individuals come from genes, environment, or both. It is often useful to ask which kind of variation a particular trait is showing.

Discontinuous variation

A trait that comes in distinct categories, with no in-between values, shows discontinuous variation.

• Usually controlled by one or a few genes
• Not normally affected by the environment
• Examples: blood group (A, B, AB, O), ability to taste PTC (taster vs non-taster), eye colour (broad categories), earlobe attached vs free

Continuous variation

A trait that varies smoothly across a continuous range, with most individuals near an average and fewer at the extremes, shows continuous variation.

• Usually polygenic (controlled by many genes acting together) and strongly influenced by the environment
• Plot the values on a graph and you get the familiar bell curve
• Examples: height (genes + nutrition + childhood illness), body mass (genes + diet + exercise), skin colour (multiple pigment genes + sunlight exposure)

Environmental variation in plants

Plants are especially sensitive to environment. Identical clones (cuttings from the same parent) grown in different conditions can end up quite different:

• A shaded plant grows taller and thinner than its sister in full sun
• A water-starved plant has smaller leaves
• A magnesium-deficient plant has yellow leaves rather than green

So the genotype is the same (they are clones) but the phenotype is different. Environment and genes both matter.