Explain how the genome encodes proteins: build the complementary strand and the messenger RNA transcribed from a DNA strand, translate codons into amino acids, and explain why cells with identical DNA differ

Learning goal: Explain cellular genetics: that each organism has a genome encoded in DNA and divided into genes, that genes code for proteins, that the sequence of DNA bases determines the sequence of amino acids, and that different cells use different parts of the same genetic instructions. Given one strand of DNA, construct the complementary strand and the messenger RNA transcribed from it, and translate the messenger RNA using a codon table.

Life is specified by genomes. A genome is the complete set of genetic information an organism carries, containing all the biological information needed to develop and maintain that organism. In every known cell that information is encoded in deoxyribonucleic acid, DNA, and organized into discrete units called genes. A gene, for this course, is a segment of a DNA molecule that codes for a protein, or occasionally for an RNA that works on its own. Most human body cells carry their nuclear DNA on 46 chromosomes, 23 inherited from each parent (gametes carry 23, mature red blood cells have no nucleus, and mitochondria hold a small DNA of their own), and the human genome contains on the order of 20,000 protein-coding genes; the exact count is still being refined. A bacterium may carry a few thousand genes on a single circular chromosome. What matters here is the relationship: genome → chromosomes → genes → proteins → traits.

The structure of DNA. DNA is a double helix built from nucleotides. Each nucleotide has a sugar (deoxyribose), a phosphate group and one of four nitrogenous bases: adenine (A), thymine (T), guanine (G) and cytosine (C). Sugars and phosphates link into two long backbones, and the bases point inward and pair across the middle: A always pairs with T, held by two hydrogen bonds, and G always pairs with C, held by three. Because of this complementary base pairing, one strand fully determines the other. The two strands run in opposite directions, which chemists label 5' to 3' and 3' to 5', so the complement of a strand is written running the opposite way. The pairing rule also explains a fact first measured by Erwin Chargaff: in double-stranded DNA the amount of A equals the amount of T and the amount of G equals the amount of C.

Replication. Before a cell divides, the helix is unwound and each strand serves as a template for a new partner strand, assembled by the enzyme DNA polymerase according to the pairing rule. Each new double helix keeps one old strand and one new one, which is why the process is called semi-conservative. Replication is what lets the genetic instructions be passed intact to every cell that develops from the original, and to offspring through gametes; the heredity lessons build on this.

From gene to protein: transcription. To make a protein, the cell first copies the gene into messenger RNA (mRNA). RNA differs from DNA in three ways: its sugar is ribose, it is usually single-stranded, and it uses uracil (U) in place of thymine, so A in the template pairs with U in the RNA. The enzyme RNA polymerase reads one strand of the gene, the template strand, and assembles a complementary mRNA. The other DNA strand, the coding strand, has the same sequence as the RNA just transcribed except for T in place of U, which is a handy check. In eukaryotic cells transcription happens in the nucleus, and the first RNA copy is processed there before it leaves: non-coding stretches called introns are cut out, so the finished mRNA that moves out to the cytoplasm matches the coding strand only with the introns removed. The short genes worked in this lesson are simplified, intron-free examples, in which the mRNA matches the coding strand base for base.

From gene to protein: translation. A ribosome reads the mRNA three bases at a time. Each triplet is a codon, and each codon specifies one amino acid or a stop signal. With four bases there are 64 possible codons for 20 amino acids, so most amino acids are specified by more than one codon; this redundancy is why many single-base changes do not alter a protein. AUG is the start codon and codes for methionine, so nearly every protein chain begins with it; UAA, UAG and UGA are stop codons that end the chain. Transfer RNA molecules carry the amino acids and match the codons through their anticodons. The amino acids are linked in codon order, the chain folds, and the folded shape gives the protein its function. Because the base sequence dictates the amino acid sequence, inserting, deleting or substituting even one segment of DNA can alter a gene and so the protein it codes for; the mutations lesson works through these changes. The whole route, DNA to RNA to protein, is often called the central dogma, and it is the link between heredity and traits: what parents pass on is DNA, and what DNA does is specify proteins.

A fully worked model. Suppose a short gene's template strand reads 3'-TACGGATTCACT-5'. The complementary DNA strand, running 5' to 3', is ATGCCTAAGTGA. The mRNA transcribed from the template is 5'-AUGCCUAAGUGA-3': it matches the coding strand with U for T. Reading codons: AUG is methionine (start); CCU is proline; AAG is lysine; UGA is stop. So this gene specifies the three-amino-acid chain methionine, proline, lysine. Real proteins run to hundreds of amino acids, but the procedure is identical at every codon. Check your work by confirming that each mRNA base is complementary to the template base beneath it: T with A, A with U, C with G, G with C.

One genome, many cell types. Every body cell of a person descends from a single fertilized egg by repeated replication and division, so all of them, apart from the gametes, carry essentially identical genetic instructions. Yet a nerve cell, a liver cell and a skin cell look and behave nothing alike. The explanation is that different parts of the genetic instructions are used in different types of cells: a liver cell transcribes genes for enzymes that process nutrients and toxins, a pancreatic beta cell transcribes the insulin gene, and a red blood cell precursor transcribes the hemoglobin genes, while each keeps the other genes switched off. Which genes are active is influenced by the cell's environment (chemical signals from neighboring cells) and its history (the choices made by its ancestors during development). Comparing the DNA sequences of two cells from the same organism finds them the same; comparing their mRNA finds them very different. Gametes are the exception in a different sense: they carry half the chromosomes, one of each pair.

Genetic information in society. Because a person's genome is inherited, it can reveal ancestry and relatedness, and because some gene variants affect health, it can indicate risks. Commercial testing companies compare a customer's DNA at many positions with reference groups and with other customers to estimate ancestry and find relatives, and some report health-related variants. The ethical questions are real: who owns the data, whether relatives who never took a test are exposed, how results might be used by employers or insurers, and how well a probabilistic risk is understood. A scientifically literate citizen can state both what such a test can show and what it cannot.

Misconceptions. "A gene is a trait" confuses cause with effect; a gene codes for a protein, and traits emerge from many proteins interacting with the environment. "RNA is just a copy of DNA" misses the chemical differences (ribose, uracil, single strand) and the fact that only a gene, not the whole genome, is transcribed at a time. "Cells in different organs have different DNA" is wrong; apart from gametes and rare mutations, they have essentially the same nuclear DNA and use it differently.

Where the rest of the standard is taught. B.H.2 is shared with the meiosis lesson. This lesson teaches the DNA half: structure, complementary strands, messenger RNA and how a base sequence fixes an amino acid sequence. The meiosis lesson teaches how sorting, recombination and crossing over in meiosis produce variation among offspring.

Investigation you can do. Extract DNA from strawberries. Mash two strawberries in a sealed bag for two minutes with 10 mL of dish soap, half a teaspoon of salt and 90 mL of water; the detergent breaks open cell and nuclear membranes and the salt helps the DNA clump. Pour the mash through a coffee filter into a cup, then gently pour an equal volume of cold rubbing alcohol down the side of the cup (goggles on; rubbing alcohol is flammable, so keep it away from any flame and use a ventilated room; nothing in this activity is to be eaten or drunk). A white, stringy mass forming at the boundary is DNA, which you can lift with a toothpick. Record what you added, how long you mashed and what you saw. The result supports the claim that cells contain a long, thread-like molecule that comes out of solution in alcohol. What the model cannot show: it cannot show the double helix, the base sequence, individual genes or which genes were active, and the strands you see are millions of molecules tangled together, not one molecule.

Worked transcription and translation from a coding strand: A gene's coding strand reads 5'-ATGTTTGGCTAG-3'. The template strand, complementary and antiparallel, is 3'-TACAAACCGATC-5'. The mRNA has the coding strand's sequence with U for T: 5'-AUGUUUGGCUAG-3'. Codons: AUG methionine (start), UUU phenylalanine, GGC glycine, UAG stop. The protein fragment is methionine-phenylalanine-glycine. Check: every mRNA base pairs with the template base below it (mRNA A with template T, U with A, G with C, C with G).

Worked Chargaff calculation: A DNA sample is 30 percent adenine. Because A pairs with T, thymine is also 30 percent. The remaining 40 percent is G and C in equal amounts, so guanine is 20 percent and cytosine 20 percent. If a second sample were reported as 30 percent A and 25 percent T, the report must be wrong for double-stranded DNA, or the sample is single-stranded DNA (as in some viruses), because pairing in a double helix forces A and T to be equal.

Worked reasoning about differentiation: A liver cell and a nerve cell from the same person are compared. Their DNA sequences are found to be identical. Their mRNA is not: the liver cell contains abundant mRNA for enzymes that break down alcohol, and the nerve cell contains none of it but has mRNA for proteins that form ion channels. Conclusion: differentiation is a difference in which genes are transcribed, not a difference in which genes are present. Prediction: if a chemical signal that normally reaches liver cells during development were delivered to the wrong cells, some liver genes might be switched on in them, which is in fact how cell identity can be experimentally reprogrammed.

Worked replication count: One fertilized egg's 46 chromosomes are replicated before each division. After one division there are 2 cells, after two divisions 4, after ten divisions 2 to the power 10, or 1,024 cells, each with a full copy of the genome. Semi-conservative replication means that after one round, every double helix has one original strand and one new strand; after two rounds, half the helices have an original strand and half are entirely new.

Supported record: Take the template strand 3'-TACCACGTGAAAATC-5' and write, one line under another, the coding DNA strand, the mRNA and the amino acid chain, using a codon table (GUG is valine, CAC is histidine, UUU is phenylalanine, UAG is stop). Then draw a diagram of the route from nucleus to ribosome and label where transcription and translation happen in a eukaryotic cell.

Independent performance: Write a short explanatory report titled "Same genome, different cells." Success criteria: (a) it defines genome, gene and protein and states the relationship among them; (b) it works one complete example from a DNA template strand of at least twelve bases through the complementary strand, the mRNA and the amino acids, with a check that every base is correctly paired; (c) it explains how a liver cell and a nerve cell can carry the same DNA and behave differently, using the words transcribed and switched off; (d) it names one influence from a cell's environment and one from its history on which genes it uses; (e) it states one thing a commercial DNA test can reveal and one ethical question it raises; (f) it describes the strawberry extraction and states two things that model cannot show.