Cells, membranes, the microscope, DNA and inheritance, microorganisms, blood and the immune system: the biology every lab career builds on.

Biology Fundamentals

## Why it matters

Most of modern biotechnology works on the path from DNA to protein. PCR copies DNA. RT-PCR (the basis of many viral tests) starts from RNA. Recombinant insulin is made by putting a human gene into cells so they translate it into protein. Biochemists study how proteins fold and work. To follow any of it, you need the **central dogma**: DNA makes RNA makes protein.

## The core idea: information flow

- **DNA** stores the information long-term in the nucleus.
- **Transcription** copies one gene into **messenger RNA (mRNA)**.
- **Translation** at the ribosome reads the mRNA and builds a chain of **amino acids**, which folds into a **protein**.

**DNA structure.** DNA is a double helix of two strands. Each strand is a chain of **nucleotides**, each with a sugar (deoxyribose), a phosphate and one of four **bases**: adenine (A), thymine (T), guanine (G) and cytosine (C). The strands are held together by base pairing: **A pairs with T, G pairs with C**. Because pairing is fixed, each strand is a template for the other, which is how DNA is copied before a cell divides.

**RNA** differs in three ways: it is usually single-stranded, its sugar is ribose, and it uses **uracil (U)** in place of thymine.

A **gene** is a stretch of DNA that codes for a functional product, usually a protein. Humans have roughly 20,000 protein-coding genes.

## Transcription

In the nucleus, the enzyme **RNA polymerase** binds to a **promoter** in front of the gene, unwinds the DNA and builds an mRNA strand complementary to the **template strand**. The mRNA ends up with the same sequence as the other DNA strand (the **coding strand**), except U replaces T.

In eukaryotes, the first transcript is processed before it leaves the nucleus: a cap and a poly-A tail are added, and non-coding **introns** are cut out (**splicing**), leaving the **exons** joined together.

## Translation and the genetic code

At the ribosome, the mRNA is read three bases at a time. Each triplet is a **codon**, and each codon stands for one amino acid or a stop signal.

- There are 4 × 4 × 4 = **64 codons** for **20 amino acids**, so most amino acids have several codons. The code is **redundant**.
- **AUG** codes for methionine and is the **start codon**.
- **UAA, UAG and UGA** are **stop codons**.
- **Transfer RNA (tRNA)** molecules carry amino acids. Each has an **anticodon** that pairs with a codon, so the right amino acid is added in the right order.

## Worked example: from gene to peptide

Coding strand of a tiny gene (5' to 3'):

```text
DNA coding strand:   ATG GGC TTT AAA TGA
DNA template strand: TAC CCG AAA TTT ACT
mRNA:                AUG GGC UUU AAA UGA
Amino acids:         Met Gly Phe Lys STOP
```

Step by step:

1. Write the mRNA by copying the coding strand and swapping T for U (or by pairing with the template strand: A→U, T→A, G→C, C→G).
2. Split the mRNA into codons from the start codon AUG.
3. Look each codon up in a codon table: AUG = Met, GGC = Gly, UUU = Phe, AAA = Lys, UGA = stop.
4. The peptide is **Met-Gly-Phe-Lys**. Translation stops at UGA, which adds no amino acid.

## From chain to working protein

The order of amino acids (the **primary structure**) determines how the chain folds into its 3D shape, and the shape determines what the protein does: an enzyme's active site, an antibody's binding pocket, a channel in the membrane. Heat, extreme pH or some chemicals can unfold (**denature**) a protein and destroy its function. That is why many lab enzymes and samples are kept cold.

## Common mistakes

- **Using T in RNA.** RNA uses U.
- **Reading codons from the wrong place.** Translation starts at AUG and reads in non-overlapping triplets; shifting by one base gives a completely different protein.
- **Thinking one gene always gives one protein.** Alternative splicing lets one gene make several related proteins.
- **Mixing up transcription and translation.** Transcription makes RNA (in the nucleus in eukaryotes); translation makes protein (at ribosomes).

## Quick recap

- DNA (A-T, G-C) stores information; RNA uses U instead of T.
- Transcription: RNA polymerase copies a gene into mRNA; introns are spliced out in eukaryotes.
- Translation: ribosomes read codons; tRNAs bring amino acids; AUG starts, UAA/UAG/UGA stop.
- 64 codons code for 20 amino acids, so the code is redundant.
- The amino acid sequence determines the fold, and the fold determines the function.


Describe how the information in DNA is transcribed into RNA and translated into protein.

DNA, genes, and proteins

Transcription and Translation: From DNA to Protein

From DNA to protein - 3D

## Why it matters

Inheritance patterns show up across lab careers. Clinical labs test for inherited conditions such as sickle cell disease and cystic fibrosis. Blood banks rely on the inheritance of ABO and Rh blood groups. Research labs breed model organisms (mice, fruit flies, plants) and must predict which offspring will carry a gene. The Punnett square is the simple tool behind all of these predictions.

## The core idea: alleles, genotypes, phenotypes

- A **gene** can come in different versions called **alleles**. For a gene with alleles **A** and **a**, a body cell has **two copies**: one from each parent.
- The pair of alleles is the **genotype**: **AA** and **aa** are **homozygous** (two of the same), **Aa** is **heterozygous**.
- The observable trait is the **phenotype**.
- A **dominant** allele (capital letter) shows its effect with one copy. A **recessive** allele (lower case) shows only when there are two copies.

Gregor Mendel's pea experiments gave two key rules:

1. **Segregation:** each parent passes on **one** of its two alleles, chosen at random, in each egg or sperm (gamete).
2. **Independent assortment:** alleles of different genes (on different chromosomes) are passed on independently of each other.

## Worked example 1: a monohybrid cross

Cystic fibrosis is recessive. Two parents are both carriers (**Aa**, where **a** is the CF allele). What are the chances for each child?

Write one parent's gametes across the top and the other's down the side, then fill each box with one allele from each:

| | **A** | **a** |
|---|---|---|
| **A** | AA | Aa |
| **a** | Aa | aa |

- Genotypes: **1 AA : 2 Aa : 1 aa**
- Phenotypes: **3 unaffected : 1 affected**
- Each child has a **1 in 4 (25%)** chance of having CF, a **1 in 2** chance of being a carrier, and a 1 in 4 chance of inheriting neither CF allele.

Note that this is a **probability for each child**. A family with four children could have zero, one or several affected children.

## Worked example 2: the test cross

A breeder has a mouse with the dominant phenotype. Is it **AA** or **Aa**? Cross it with a homozygous recessive (**aa**) mouse.

- If it is **AA**: every offspring is **Aa** and shows the dominant phenotype.
- If it is **Aa**: half the offspring are **Aa** and half are **aa** (recessive phenotype).

Seeing even one recessive offspring shows the parent is heterozygous. This is a standard tool in research animal facilities.

## Beyond simple dominance

Many traits do not follow the simple pattern:

- **Codominance:** both alleles show. ABO blood groups have alleles I^A, I^B and i. A person with I^A I^B is blood group **AB**, with both A and B antigens on their red cells.
- **Incomplete dominance:** the heterozygote is in between, like pink flowers from red × white snapdragons.
- **Sex-linked traits:** genes on the X chromosome, such as those for haemophilia A and red-green colour blindness, show up more often in males, who have one X.
- **Polygenic traits:** height and skin colour depend on many genes plus environment.

## Thinking like a programmer

A Punnett square is just "every allele from parent 1 combined with every allele from parent 2". That is two nested loops. In the Do activity, you finish a short Python function that does exactly that and counts the results. One detail matters: **Aa** and **aA** are the same genotype, so the code must write the dominant allele first before counting.

## Common mistakes

- **Putting both of a parent's alleles in one gamete.** Each gamete gets one allele.
- **Reading a ratio as a guarantee.** 3:1 is a probability per offspring, not an exact count in a small family.
- **Assuming dominant means common.** Some dominant alleles, such as the one for Huntington's disease, are rare.
- **Counting "aA" separately from "Aa".** They are the same heterozygous genotype.

## Quick recap

- Each parent passes one allele per gene to each offspring.
- A Punnett square combines every gamete from one parent with every gamete from the other.
- Aa × Aa gives 1 AA : 2 Aa : 1 aa, or 3 dominant : 1 recessive.
- A test cross with aa reveals whether a dominant-looking parent is AA or Aa.
- Codominance, incomplete dominance, sex linkage and polygenic traits extend the simple rules.

## Try it

Open the **Do** tab and complete a Python Punnett square counter.


Use Punnett squares to predict the genotypes and phenotypes of offspring from a one-gene cross.

Inheritance

Mendelian Genetics and Punnett Squares

Punnett Square Basics | Mendelian Genetic Crosses

## Why it matters

Genetic testing, cancer diagnostics, antibiotic resistance and vaccine updates all come down to **mutations**: changes in a DNA sequence. A molecular lab might sequence a tumour to find a mutation that guides treatment, or test bacteria for a resistance gene. To read such a result you need to know what kinds of mutation exist and what each does to the protein.

## The core idea

A **mutation** is any change in the DNA base sequence. Because the protein is built by reading the DNA in codons (three-base words), the effect depends on how the change affects those words.

Mutations arise from:

- **Copying errors** during DNA replication (rare, because DNA polymerase proofreads).
- **Mutagens:** UV light, tobacco smoke chemicals, some radiation.
- **Spontaneous chemical damage** to bases.

Cells have repair systems that fix most damage. What remains can be harmful, neutral or, occasionally, useful.

## Point mutations: one base changed

Take this stretch of mRNA and its protein:

```text
mRNA:     AUG  GAG  UGG  AAA
Protein:  Met  Glu  Trp  Lys
```

Change one base at a time:

| Type | Change | New codon | Effect |
|---|---|---|---|
| **Silent** | GAG → GA**A** | GAA = Glu | same amino acid; usually no effect (the code is redundant) |
| **Missense** | GAG → G**U**G | GUG = Val | one amino acid swapped; effect ranges from none to severe |
| **Nonsense** | UGG → UG**A** | UGA = stop | protein cut short; usually loses function |

**Worked example: sickle cell disease.** In the β-globin gene of haemoglobin, one A is replaced by T in the DNA. The mRNA codon changes from GAG to GUG, so the sixth amino acid changes from **glutamic acid to valine**. This single missense change makes haemoglobin stick together when oxygen is low, distorting red cells into a sickle shape. One base, one amino acid, a serious disease. Labs detect it with haemoglobin electrophoresis, HPLC or DNA tests.

## Insertions and deletions: frameshifts

Adding or removing bases that are **not a multiple of three** shifts the **reading frame**, so every codon after the change is different. An English analogy:

```text
Original:          THE CAT ATE THE RAT
Delete one "A":    THE CTA TET HER AT...
```

```text
mRNA:              AUG GAG UGG AAA
Delete first G:    AUG AGU GGA AA...
Protein:           Met Ser Gly ...   (every amino acid after the change is different)
```

Frameshifts usually produce a useless protein and often reach a premature stop codon. Deleting exactly three bases removes one amino acid without a frameshift. The most common cystic fibrosis variant, **ΔF508**, is a three-base deletion that removes one phenylalanine from the CFTR protein, causing it to misfold.

## Larger changes

Mutations can also affect chromosomes: duplications, deletions of whole segments, or **translocations** where pieces of two chromosomes swap. The "Philadelphia chromosome" in chronic myeloid leukaemia is a translocation between chromosomes 9 and 22 that creates a fusion gene; detecting it guides treatment.

## Where variation comes from

Mutation is the original source of all new alleles. Sexual reproduction then shuffles them:

- **Independent assortment** of chromosomes into gametes.
- **Crossing over**, where paired chromosomes swap segments during meiosis.
- **Random fertilisation**: any sperm with any egg.

Most variation between people is harmless. When a variant is common (found in more than about 1% of a population) it is often called a **polymorphism**. Clinical reports classify variants as pathogenic, likely pathogenic, of uncertain significance, likely benign or benign.

Mutations that occur in body cells (**somatic**) are not inherited but can cause cancer. Mutations in eggs or sperm (**germline**) can be passed to children.

## Mutation and microbes

Bacteria and viruses reproduce quickly, so useful mutations spread fast. A mutation that lets a bacterium survive an antibiotic is **selected** when that antibiotic is used, and the resistant strain takes over. RNA viruses such as influenza mutate quickly, which is one reason flu vaccines are updated each year.

## Common mistakes

- **Assuming every mutation is harmful.** Many are silent or neutral, and some are beneficial.
- **Thinking a missense change is always mild.** Sickle cell shows one amino acid can matter a lot.
- **Calling any deletion a frameshift.** Only deletions or insertions that are not multiples of three shift the frame.
- **Mixing up somatic and germline.** Only germline mutations are inherited.

## Quick recap

- A mutation is a change in DNA sequence; repair fixes most damage.
- Silent: same amino acid. Missense: different amino acid. Nonsense: early stop.
- Insertions or deletions that are not a multiple of three cause frameshifts.
- Sickle cell is a single missense change; CF ΔF508 is a three-base deletion.
- Mutation creates new alleles; meiosis and fertilisation shuffle them.


Explain how point mutations, insertions and deletions change a protein, and where genetic variation comes from.

Mutations and variation

Mutations (Updated)

Follow information from DNA to protein, predict inheritance with Punnett squares, and see how mutations change proteins.