---
title: "Gene Expression: Transcription and Translation"
book: "University Biology — Year 1"
subject: biology
language: en
chapter: 19
exercises: 12
source: https://one-course.com/books/biology/3/en/chapter/19-gene-expression-transcription-and-translation
---

# Chapter 19 — Gene Expression: Transcription and Translation

A [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) of thirty thousand [base pairs](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#thm-b1-nucleic-acids-helix) is read in a quarter of an hour into a working copy, cut down to two thousand letters, shipped out of the nucleus, and translated by twenty-five [ribosomes](#def-b1-gene-expression-ribosome) at once into a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of five hundred [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) — one every four seconds, for as long as the copy lasts. The [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) spends more energy on this than on anything else it does. This chapter follows the information from [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) to [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide): the copying of a [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) into [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain), the editing of that [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) in eukaryotes, the code that maps triplets of bases onto [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid), the [ribosome](#def-b1-gene-expression-ribosome) that reads it, and what happens to a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) once it is made.

## 19.1 From gene to protein

**Proposition 19.1 (The flow of information).**

Genetic information flows from [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) to [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) to [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide). *Transcription* copies one strand of a [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) into an [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) of the same sequence as the other strand (with U for T); *translation* reads the [messenger RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) three bases at a time and assembles the corresponding [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) into a [polypeptide](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide). Every step uses the pairing of bases: [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) with [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) in transcription, messenger with [transfer RNA](#def-b1-gene-expression-trna) in translation. The sequence of a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) is thus a transcript of the sequence of its [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene), and a change of one base can change one [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) — the link between mutation and phenotype. Information does not flow back from [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) to nucleic acid; the one reverse step, [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) copied into [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) by retroviruses, does not touch [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide).

## 19.2 Transcription

**Definition 19.2 (RNA polymerase, promoter, transcription).**

*[RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) polymerase* synthesises [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) on a [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) template, $5' \to 3'$, from the four ribonucleoside triphosphates, without a primer. It starts at a *promoter*, a sequence just upstream of the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) that it recognises and binds; in bacteria a subunit called $\sigma$ (*sigma*) does the recognising, at two conserved stretches ten and thirty-five pairs before the start. The [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) opens about fifteen pairs of the helix into a *transcription bubble*, copies the *template strand* (read $3' \to 5'$) into an [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) identical in sequence to the other, *coding* strand, and moves along at about fifty [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) a second, re-closing the helix behind it; the [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) peels off as it is made. It stops at a *terminator*: in bacteria a self-complementary sequence whose [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) folds into a hairpin that pulls the transcript free. Many polymerases can follow one another along a [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene), so a transcript can be started every second.

![Transcription. The polymerase opens a bubble, pairs ribonucleotides to the template strand and joins them 5' 3'; the RNA leaves through a channel as the enzyme advances.](https://one-course.com/images/onecourse/chapters/biology-3/b1-gene-expression/fig-ea369d4086c0.svg)

*Transcription. The polymerase opens a bubble, pairs ribonucleotides to the template strand and joins them $5' \to 3'$; the [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) [leaves](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) through a [channel](https://one-course.com/books/biology/3/en/chapter/7-membranes-and-membrane-transport#def-b1-membranes-transport-transporters) as the [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) advances.*

**Proposition 19.3 (Eukaryotic transcription and RNA processing).**

Eukaryotes have three polymerases: I for the large [ribosomal RNAs](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas), II for [messenger RNAs](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas), III for transfer and small [RNAs](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain). Polymerase II does not recognise its [promoter](#def-b1-gene-expression-transcription) alone: a set of *general transcription factors* assembles on it (at a TATA sequence about thirty pairs upstream in many [genes](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene)) and recruits the [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme), and regulatory [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) bound near or far modulate the rate ([Chapter 20](https://one-course.com/books/biology/3/en/chapter/20-control-of-gene-expression#ch-b1-expression-control)). The primary transcript is *processed* in the nucleus: a modified guanine *cap* is added to the $5'$ end, a tail of some two hundred adenines (*poly-A*) to the $3'$ end, and the [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) are removed by *splicing* — a complex of small [RNAs](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) and [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide), the *spliceosome*, recognises the GU at each [intron](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene)’s start and the AG at its end, cuts, and joins the [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene). Only then is the mature messenger exported to the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle). Many [genes](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) are spliced in more than one way (*alternative splicing*), so that one [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) yields several [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide); the twenty thousand human [genes](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) make perhaps a hundred thousand.

**Evidence.** Sharp and Roberts (1977) hybridised a viral [messenger RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) to the [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) of its [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) and looked at the hybrids in the [electron microscope](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#prop-b1-cell-unit-of-life-microscopes): the [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) paired with the [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) in several stretches, and between them the [DNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) looped out unpaired — the [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene), present in the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) and absent from the message. Bacterial [genes](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene), treated the same way, gave no loops. The size of a [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene)’s primary transcript, measured in the nucleus, matches the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene); the size of the cytoplasmic messenger matches the [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) alone. ∎

![From gene to messenger in a eukaryote: the whole gene is transcribed, then the introns are cut out and the exons joined, a cap and a poly-A tail are added, and the mature message leaves the nucleus.](https://one-course.com/images/onecourse/chapters/biology-3/b1-gene-expression/fig-270f2f81a918.svg)

*From [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) to messenger in a eukaryote: the whole [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) is transcribed, then the [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) are cut out and the [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) joined, a cap and a [poly-A tail](#prop-b1-gene-expression-processing) are added, and the mature message [leaves](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) the nucleus.*

## 19.3 The genetic code

**Definition 19.4 (The genetic code).**

The *genetic code* maps triplets of messenger bases, *codons*, onto [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid). Of the 64 codons, 61 specify the twenty [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) and three (UAA, UAG, UGA) are *stop* signals; AUG specifies methionine and is also the *start* codon, so every new [polypeptide](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) begins with methionine. The code is *degenerate* — most [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) have several codons, differing mostly at the third position — *non-overlapping*, read without punctuation in a *reading frame* fixed by the start codon, and almost *universal*, the same in bacteria, plants and animals with minor variants in [mitochondria](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-mitochondrion): a human [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) put into a bacterium is read correctly.

*The [genetic code](#def-b1-gene-expression-code). Each [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) lists the four [codons](#def-b1-gene-expression-code) with the given first and second bases and third base U, C, A, G in order. AUG is methionine and the start signal; UAA, UAG and UGA are stops. The third base often does not matter: the code is degenerate.*

**Proposition 19.5 (How the code was read).**

The code is a non-overlapping triplet code, and each [codon](#def-b1-gene-expression-code)’s meaning can be determined by chemistry.

**Evidence.** Crick and Brenner (1961) made mutations in a phage [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) that added or removed one base: one such change destroyed the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene)’s function, as did two, but three insertions (or three deletions) close together restored it — the message is read in threes, from a fixed starting point, and an insertion shifts the frame of everything downstream. Nirenberg and Matthaei (1961) added a synthetic [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) of uracils only to a cell-free extract of *E. coli* with the twenty [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid): it made a chain of phenylalanine only, so UUU means Phe; other synthetic messengers, and then binding of single trinucleotides to [ribosomes](#def-b1-gene-expression-ribosome) with their [transfer RNAs](#def-b1-gene-expression-trna), assigned all sixty-four by 1966. ∎

**Example 19.6 (Reading a message).**

The messenger $5'$-…GCAUGGCUUUCGGAUAA…-$3'$ is read from the AUG: AUG GCU UUC GGA UAA — Met-Ala-Phe-Gly-stop: a peptide of four residues. Delete the first G after AUG and the frame shifts: AUG CUU UCG GAU AA… — Met-Leu-Ser-Asp…, a different [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of a different length. Change UUC to UUU and nothing changes: both are Phe, a *silent* mutation.

## 19.4 Translation

**Definition 19.7 (Transfer RNA and its synthetases).**

A *transfer [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain)* ([Chapter 11](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#ch-b1-nucleic-acids)) is the adaptor between [codon](#def-b1-gene-expression-code) and [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid): its *anticodon*, three bases in a loop, pairs antiparallel with a [codon](#def-b1-gene-expression-code) of the message, and its $3'$ end carries the corresponding [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid). The pairing at the third [codon](#def-b1-gene-expression-code) position is loose (*wobble*), so about forty tRNAs suffice for sixty-one [codons](#def-b1-gene-expression-code). Each tRNA is loaded by its own *aminoacyl-tRNA synthetase*, an [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) that recognises both the [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) and the tRNA and joins them in two steps at the cost of one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) (split to AMP: two high-energy bonds), proofreading the [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) as it does so. These twenty [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) are where the code is actually implemented: the [ribosome](#def-b1-gene-expression-ribosome) does not check which [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) a tRNA carries, only that its anticodon matches.

**Definition 19.8 (The ribosome).**

The *ribosome* is a particle of two subunits, each of [ribosomal RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) and [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) (in bacteria: a small 30S subunit and a large 50S subunit, together 70S, $2.5\,\mathrm{MDa}$; eukaryotic ribosomes are larger, 80S). The small subunit binds the messenger and decodes it; the large subunit holds the tRNAs and forms the [peptide bond](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) — the catalyst is the [ribosomal RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) itself. Three tRNA sites span both subunits: A (aminoacyl, where the next charged tRNA enters), P (peptidyl, holding the growing chain), E (exit).

![The ribosome: two subunits clamped on the messenger, two transfer RNAs in the cleft, the growing chain leaving through a tunnel in the large subunit.](https://one-course.com/images/onecourse/chapters/biology-3/b1-gene-expression/fig-a1fd8fe6355d.svg)

*The [ribosome](#def-b1-gene-expression-ribosome): two subunits clamped on the messenger, two [transfer RNAs](#def-b1-gene-expression-trna) in the cleft, the growing chain leaving through a tunnel in the large subunit.*

**Proposition 19.9 (The cycle of elongation).**

Translation starts when the small subunit finds the start [codon](#def-b1-gene-expression-code) — in bacteria by pairing a [ribosomal RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) sequence with a site just upstream of the AUG, in eukaryotes by binding the cap and scanning to the first AUG — and the initiator tRNA (methionine) settles in the P site; the large subunit then joins. Each round of *elongation* adds one residue: a charged tRNA whose [anticodon](#def-b1-gene-expression-trna) matches the A-site [codon](#def-b1-gene-expression-code) is delivered by an elongation factor and checked (one GTP); the [ribosomal RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) of the large subunit transfers the growing chain from the P-site tRNA onto the [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) of the A-site tRNA, forming the [peptide bond](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide); the [ribosome](#def-b1-gene-expression-ribosome) moves one [codon](#def-b1-gene-expression-code) along (a second GTP), shifting the tRNAs to P and E, and the empty one [leaves](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs). At a stop [codon](#def-b1-gene-expression-code) a *release factor* enters the A site and the chain is hydrolysed free. Bacterial [ribosomes](#def-b1-gene-expression-ribosome) add fifteen to twenty residues a second, eukaryotic ones two to five; several [ribosomes](#def-b1-gene-expression-ribosome) read one message at once, forming a *polysome*.

![One round of elongation. A charged tRNA is admitted to the A site when its anticodon matches; the ribosomal RNA joins the chain to its amino acid; the ribosome moves on by one codon, and the empty tRNA leaves. Two GTP per residue, plus the two high-energy bonds spent in charging the tRNA.](https://one-course.com/images/onecourse/chapters/biology-3/b1-gene-expression/fig-12d70c182dc7.svg)

*One round of elongation. A charged tRNA is admitted to the A site when its [anticodon](#def-b1-gene-expression-trna) matches; the [ribosomal RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-rnas) joins the chain to its [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid); the [ribosome](#def-b1-gene-expression-ribosome) moves on by one [codon](#def-b1-gene-expression-code), and the empty tRNA [leaves](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs). Two GTP per residue, plus the two high-energy bonds spent in charging the tRNA.*

![Polysomes under the electron microscope: ribosomes strung along a messenger, each making its own copy of the protein.](https://one-course.com/images/onecourse/chapters/biology-3/b1-gene-expression/img-88785778b81b.jpg)

*Polysomes under the [electron microscope](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#prop-b1-cell-unit-of-life-microscopes): [ribosomes](#def-b1-gene-expression-ribosome) strung along a messenger, each making its own copy of the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide).*

**Method 19.10 (Reckoning a protein’s synthesis).**

1. Length: a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of $n$ residues needs a coding sequence of $3n + 3$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) (the stop [codon](#def-b1-gene-expression-code) included), inside a messenger longer by its untranslated ends and, in the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) , by its [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) .
2. Time: divide $n$ by the elongation rate ( $15\text{ to }20\,$ per second in bacteria, $2\text{ to }5\,$ in eukaryotes); the message is being read by one [ribosome](#def-b1-gene-expression-ribosome) every $80\text{ to }100\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) , so the output per message is one chain every (spacing / rate) seconds.
3. Energy: four high-energy phosphate bonds per residue (two to charge the tRNA, two GTP on the [ribosome](#def-b1-gene-expression-ribosome) ), plus the transcription of the message at two per [nucleotide](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) , shared among all the chains that message yields.
4. Fidelity: about one wrong [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) in $10^4$ [codons](#def-b1-gene-expression-code) ; a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of $500\,$ residues is wrong somewhere in one copy out of twenty — tolerable because [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) are replaceable and errors are not inherited.

## 19.5 After translation

**Proposition 19.11 (What happens to a new polypeptide).**

The chain folds as it emerges, helped by [chaperones](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#prop-b1-proteins-denaturation) ([Chapter 12](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#ch-b1-proteins)). Its destination is written in its sequence: a *[signal peptide](#prop-b1-gene-expression-after)* at the N-terminus binds a *signal recognition particle* that halts translation, docks the [ribosome](#def-b1-gene-expression-ribosome) on the [endoplasmic reticulum](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-endomembrane), and threads the chain into its lumen ([Chapter 6](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#ch-b1-eukaryotic-cell)); other sequences direct [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) into [mitochondria](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-mitochondrion), [chloroplasts](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-plastid), the nucleus or [peroxisomes](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-peroxisome) after synthesis; a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) with no signal stays in the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle). Many [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) are *modified*: the initial methionine removed, sugars attached in the ER and [Golgi](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-endomembrane), phosphates added and removed by kinases and phosphatases, [lipids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) attached, pieces cut out (insulin is made as one chain and cut into two; zymogens are cut to activate them). And every [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) is eventually *degraded*: tagged with the small [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) *ubiquitin* and unfolded and digested by the *proteasome*, after a life of minutes (regulatory [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide)) to months (haemoglobin) — so that the [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) present are those the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) is currently making.

**Example 19.12 (The numbers of a cell).**

A growing *E. coli* holds some $20\,000$ [ribosomes](#def-b1-gene-expression-ribosome), each adding twenty residues a second: $4 \times 10^{5}$ residues a second, a million [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of $300\,$ residues in an hour — its own content, which is what doubling every hour requires. Half its energy goes to [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) synthesis. A liver [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) holds ten million [ribosomes](#def-b1-gene-expression-ribosome) and makes [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) for weeks of use rather than for division; a plasma [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell), secreting antibody, devotes nearly all of them to one [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) and pours out two thousand molecules a second.

## 19.6 Exercises

**Exercise 19.1 ★.**

Give the [RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) transcribed from the template strand $3'$-TACGGATTC-$5'$, and the coding strand.

**Solution of Exercise 19.1.**

[RNA](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-chain) $5'$-AUGCCUAAG-$3'$; coding strand $5'$-ATGCCTAAG-$3'$.

**Exercise 19.2 ★.**

List the three modifications a eukaryotic primary transcript undergoes before it [leaves](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) the nucleus.

**Solution of Exercise 19.2.**

A $5'$ cap (modified guanine), a $3'$ [poly-A tail](#prop-b1-gene-expression-processing), and the removal of the [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) by splicing.

**Exercise 19.3 ★.**

Using the code table, translate $5'$-AUGCCGAAAGUUUGA-$3'$.

**Solution of Exercise 19.3.**

AUG CCG AAA GUU UGA: Met-Pro-Lys-Val, then stop.

**Exercise 19.4 ★.**

Name the three tRNA sites of the [ribosome](#def-b1-gene-expression-ribosome) and what happens in each.

**Solution of Exercise 19.4.**

A: the incoming charged tRNA is admitted and checked. P: the tRNA carrying the growing chain; the bond forms between its chain and the A-site [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid). E: the emptied tRNA on its way out.

**Exercise 19.5 ★★.**

A messenger of $2400\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) has $150\,$ of $5'$ untranslated region and $450\,$ of $3'$ untranslated region and poly-A. How many residues has the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide)? How long does one [ribosome](#def-b1-gene-expression-ribosome) take to make it at four residues a second, and how many [ribosomes](#def-b1-gene-expression-ribosome) can read the message at once at one per $90\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide)?

**Solution of Exercise 19.5.**

Coding $2400 - 600 = 1800$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide): 599 residues (600 [codons](#def-b1-gene-expression-code), one a stop). Time $599/4 = 150\,\mathrm{s}$. [Ribosomes](#def-b1-gene-expression-ribosome) $1800/90 = 20$ at once.

**Exercise 19.6 ★★.**

Explain why three insertions restore a [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene)’s [reading frame](#def-b1-gene-expression-code) while one or two do not, and what the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) made from the triple insertion looks like.

**Solution of Exercise 19.6.**

The message is read in threes from a fixed start; one or two extra bases shift every [codon](#def-b1-gene-expression-code) downstream and the rest of the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) is gibberish, usually ending at a premature stop. Three extra bases add one [codon](#def-b1-gene-expression-code) and restore the frame: the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) has one extra residue and a few wrong ones between the insertions, and often still works.

**Exercise 19.7 ★★.**

A mutation changes the [codon](#def-b1-gene-expression-code) CAG to UAG in the middle of a [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) of $300\,$ [codons](#def-b1-gene-expression-code); another changes CAG to CAA; a third changes it to CGG. Give the effect of each on the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide).

**Solution of Exercise 19.7.**

CAG (Gln) to UAG (stop): the chain ends at residue 150, a truncated, almost certainly inactive [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) (nonsense mutation). CAG to CAA: still Gln, silent. CAG to CGG: Arg for Gln, a substitution (missense) whose effect depends on the position.

**Exercise 19.8 ★★.**

Explain why the fidelity of translation rests on the [aminoacyl-tRNA synthetases](#def-b1-gene-expression-trna) rather than on the [ribosome](#def-b1-gene-expression-ribosome), and describe an experiment that showed it (a cysteine attached to its tRNA is chemically converted to alanine; where does the alanine end up?).

**Solution of Exercise 19.8.**

The [ribosome](#def-b1-gene-expression-ribosome) checks only the codon–anticodon pairing; it cannot see the [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid). If cysteine on its tRNA is converted chemically to alanine, the [ribosome](#def-b1-gene-expression-ribosome) inserts alanine wherever the message says cysteine: the tRNA, not the [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid), is read. Hence the synthetase, which pairs each [amino acid](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) with the right tRNA, is the true translator.

**Exercise 19.9 ★★.**

Compute the energy cost, in high-energy bonds, of a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of $400\,$ residues, and the fraction of it spent on the [ribosome](#def-b1-gene-expression-ribosome).

**Solution of Exercise 19.9.**

$400\times 4 = 1600$ bonds; the [ribosome](#def-b1-gene-expression-ribosome)’s two GTP per residue are half of it, the synthetases’ two the other half.

**Exercise 19.10 ★★★.**

In bacteria [ribosomes](#def-b1-gene-expression-ribosome) begin translating a message while it is still being transcribed; in eukaryotes they cannot. Explain why (two reasons), and what this difference makes possible in eukaryotes.

**Solution of Exercise 19.10.**

In eukaryotes the transcript is made in the nucleus and the [ribosomes](#def-b1-gene-expression-ribosome) are in the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle), separated by the envelope; and the transcript is not a messenger until it has been spliced and capped. The separation makes possible the processing itself — alternative splicing, the control of export, and a check that the message is complete before it is read.

**Exercise 19.11 ★★★.**

A [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) of five [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) can be spliced to include or skip [exon](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) 3 ($90\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide)) and [exon](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) 4 ($100\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide)). List the possible messengers and say which ones keep the [reading frame](#def-b1-gene-expression-code) of [exon](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) 5. What does this show about alternative splicing?

**Solution of Exercise 19.11.**

Four messengers: with both [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) (190 [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) added), with 3 only (90), with 4 only (100), with neither (0). A frame is kept if the added length is a multiple of 3: 0 and 90 keep it; 100 and 190 shift it, so the messengers with [exon](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) 4 alone or both [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) read [exon](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) 5 out of frame and truncate the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide). Alternative splicing must respect the frame, and [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) are often multiples of three for that reason.

**Exercise 19.12 ★★★.**

“The code is a frozen accident: arbitrary, but too costly to change.” Discuss in a paragraph: what in the code looks arbitrary, what looks optimised (the third position, similar [codons](#def-b1-gene-expression-code) for similar [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid)), and why a mutation changing a synthetase’s specificity is almost always lethal.

**Solution of Exercise 19.12.**

Arbitrary: nothing in chemistry says that UUU must mean Phe; the assignments are conventions held by the synthetases. Optimised: the third position is the most degenerate, so the errors and mutations that fall there are often silent, and [codons](#def-b1-gene-expression-code) that differ by one base tend to encode similar [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid), so a substitution is often mild — the code minimises the damage of error. Frozen: a synthetase that changed its specificity would alter every [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) at once, thousands of them, in the same instant; almost no [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) survives that, so the code cannot drift and has been fixed since the common ancestor of all living things.

## 19.7 Problem: From a Gene to a Protein

**Problem 19.1.**

Weekend problem — a thirty-kilobase gene followed into a five-hundred-residue protein: transcription timed, splicing weighed, ribosomes counted, energy and errors reckoned, ending on the cost of one protein in ATP

A human [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) spans $30\,\mathrm{kb}$ with eight [exons](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) totalling $2000\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) of mature messenger, of which $1503\,$ code (500 residues plus the stop). Polymerase II transcribes at $30\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) per second; [ribosomes](#def-b1-gene-expression-ribosome) elongate at $4\,$ residues per second and space themselves one per $80\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide); the messenger’s half-life is $2\,\mathrm{h}$. Costs: two high-energy bonds per [nucleotide](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) transcribed, four per residue translated; take one high-energy bond as one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp). Error rates: $10^{-5}$ per [nucleotide](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) transcribed, $10^{-4}$ per [codon](#def-b1-gene-expression-code) translated.

**Part I — Transcription and splicing.**

1. How long does one polymerase take to transcribe the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) ?
2. What fraction of the primary transcript is removed by splicing?
3. How many [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) are transcribed for every [nucleotide](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) of mature messenger?
4. Compute the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) spent transcribing one primary transcript.
5. If a polymerase starts every $10\,\mathrm{s}$ , how many polymerases are on the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) at once, and how many messengers does the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) produce per hour?
6. Compute the number of [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) and their mean length.
7. The spliceosome removes each [intron](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) in about a minute, in parallel. Does splicing or transcription set the time from [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) to messenger?
8. Compute the physical length of the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) and of the mature messenger ( $0.34\,\mathrm{nm}$ per [nucleotide](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) ).

**Part II — Translation.**

9. How long does one [ribosome](#def-b1-gene-expression-ribosome) take to translate the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) ?
10. How many [ribosomes](#def-b1-gene-expression-ribosome) read one messenger at once?
11. How many [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) molecules does one messenger yield per hour?
12. Over its $2\,\mathrm{h}$ half-life, how many does it yield in all (a message with half-life $t_{1/2}$ yields, on average, $t_{1/2}/\ln 2$ hours of full production)?
13. Compute the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) spent translating one [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) .
14. Compute the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) spent on transcription per [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) , sharing the transcript’s cost among the [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) of question 12.
15. Compute the total cost of one [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) and the fraction due to translation.

**Part III — Errors.**

16. Compute the probability that a given messenger carries at least one transcription error in its $1503\,$ coding [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) .
17. Compute the probability that a given [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) molecule carries at least one translation error.
18. About a quarter of [nucleotide](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) changes are silent and a third of amino-acid substitutions are harmless. What fraction of the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) molecules made are defective?
19. A defective messenger yields defective [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) for two hours; a defective [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) is one molecule. Explain why the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) can afford a translation error rate ten times the transcription rate, and both far above the replication rate.

**Part IV — The [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell)’s budget.** The [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) makes $3000$ copies of this [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) per hour, and in all $3 \times 10^{9}$ residues of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) per day.

20. How many messengers of this [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) must be present at once (each yielding the number of question 11)?
21. How many [ribosomes](#def-b1-gene-expression-ribosome) are occupied by this [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) ?
22. Compute the daily [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) spends on all its [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) synthesis (four per residue) and, at $50\,\mathrm{kJ}/\mathrm{mol}$ , the power in watts for a [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) of $2000\,\text{µ}\mathrm{m}^{3}$ .
23. Compare with the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) ’s total power if it consumes $1 \times 10^{9}\,$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per second.
24. A drug blocks the spliceosome. Predict its effect on this [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) and on a bacterial [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) .
25. State the result: the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) cost of one molecule of the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) , split between translation and transcription, and the time from the start of transcription to the first finished [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) .

**Solution of Problem 19.1.**

**1.** $30\,000/30 = 1000\,\mathrm{s}$, about $17\,\mathrm{min}$. **2.** $28\,000/30\,000 = 93\,\%$. **3.** $30\,000/2000 = 15$. **4.** $2\times 30\,000 = 60\,000$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp). **5.** $1000/10 = 100$ polymerases on the [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene); 360 messengers per hour. **6.** Seven [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene), mean $28\,000/7 = 4000\,$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide). **7.** Transcription ($17\,\mathrm{min}$); the [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) are spliced as they are made, and the last one adds only a minute. **8.** [Gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) $30\,000\times 0.34\,\mathrm{nm} = 10\,\text{µ}\mathrm{m}$; messenger $0.68\,\text{µ}\mathrm{m}$. **9.** $500/4 = 125\,\mathrm{s}$. **10.** $2000/80 = 25$. **11.** One chain finishes every $80/4 = 20\,\mathrm{s}$: 180 per hour. **12.** $2/\ln 2 = 2.9\,\mathrm{h}$ of full production: about 520 [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide). **13.** $4\times 500 = 2000$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp). **14.** $60\,000/520 = 115$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide). **15.** About 2100 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp), $95\,\%$ of it in translation. **16.** $1 - (1 - 10^{-5})^{1503} \approx 1503\times 10^{-5} =
1.5\,\%$. **17.** $1 - (1 - 10^{-4})^{500} \approx 5\,\%$. **18.** Transcription: $1.5\%\times 0.75\times 0.67 \approx
0.75\%$ of messengers defective, hence of [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide); translation: $5\%\times 0.67 = 3.3\%$; about $4\,\%$ of the molecules. **19.** A [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) error is confined to one molecule, which is soon degraded; a messenger error is copied into hundreds of [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide); a replication error is inherited by every descendant for ever. The cost of an error, and hence the accuracy worth paying for, rises at each step back. **20.** $3000/180 = 17$ messengers present. **21.** $17\times 25 = 420$ [ribosomes](#def-b1-gene-expression-ribosome). **22.** $3 \times 10^{9}\times 4 = 1.2 \times 10^{10}$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per day $= 2 \times 10^{-14}\,\mathrm{mol}$, $1 \times 10^{-9}\,\mathrm{J}$ per day, i.e. $1.2 \times 10^{-14}\,\mathrm{W}$ — $6\,\mathrm{fW}$ per cubic micrometre. **23.** $10^9$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per second is $8.6 \times 10^{13}$ per day: [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) synthesis is a hundredth of it in this slowly renewing [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) (in a dividing bacterium it is half). **24.** No mature messenger: the primary transcripts accumulate in the nucleus and the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) disappears as its messengers decay, within hours. The bacterial [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide), whose [gene](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene) has no [introns](https://one-course.com/books/biology/3/en/chapter/17-genomes-of-cells-and-viruses#def-b1-genomes-gene), is unaffected. **25.** About 2100 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per molecule — 2000 for translation, a hundred for its share of the transcript; first [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) after $1000\,\mathrm{s}$ of transcription, a minute of processing and export, and $125\,\mathrm{s}$ of translation: about twenty minutes.