Molecular Genetics: One Mark Questions, Book Back Answers and Notes

About Molecular Genetics

Medium ~120 min study

Classical genetics worked out the patterns in which traits are inherited by watching visible characters. Molecular genetics explains what is actually happening inside the cell: which molecule carries the information, how it is copied and how it is read. This chapter first shows how scientists proved that DNA, not protein, is the genetic material, and then looks at the molecule itself.

The chapter is built around the central dogma: information flows from DNA to RNA to protein. Along the way you study the chemistry of nucleotides, how the double helix is copied semi-conservatively, how mRNA is made in transcription and how ribosomes use it to build proteins in translation. The lac operon then shows how a bacterium switches genes on only when it needs them.

Exam questions often ask for the steps of protein synthesis, the properties of the genetic code, the role of each part of the lac operon, and the name of the scientist behind each experiment. The applications at the end, the Human Genome Project and DNA fingerprinting, also carry direct questions, so do not leave them for last.

What you'll learn

• Describe the experiments that established DNA as the genetic material.
• Explain the chemical composition and structure of DNA and RNA, including base pairing.
• Describe the enzymes and steps of semi-conservative DNA replication.
• Explain transcription and compare RNA processing in prokaryotes and eukaryotes.
• Use the genetic code to translate an mRNA sequence into a chain of amino acids.
• Explain how the lac operon is switched off and on in bacteria.
• Describe the method and uses of DNA fingerprinting and the aims of the Human Genome Project.

Before you start

• Cell structure, cell division and how chromosomes behave in mitosis and meiosis.
• Mendelian inheritance and basic genetic terms such as gene, allele and genotype.
• Biomolecules, particularly proteins, lipids and simple carbohydrates.

Molecular Genetics explained

From DNA to Protein

The Search for Genetic Material

For a long time many scientists believed proteins carried hereditary information, because proteins are so varied. Two lines of experiment settled the question. Bacterial transformation experiments showed that a chemical from dead bacteria could permanently change living bacteria, and that this chemical was DNA. Hershey and Chase's work with bacteriophages showed that it is the viral DNA, not the protein coat, that enters the bacterium and directs the making of new viruses. After this, research turned to the structure and chemistry of nucleic acids.

Structure and Chemistry of Nucleic Acids

Nucleic acids are long chains of nucleotides. Each nucleotide has a nitrogenous base, a pentose sugar and a phosphate group. In the double helix model of DNA, the two strands run antiparallel and are held together by complementary base pairing: adenine with thymine, and guanine with cytosine. DNA is chemically stable, which suits long-term storage of information. RNA is more reactive, can act as a catalyst and is thought to have been the first genetic material; in cells today it works mainly as a messenger and in protein synthesis.

Semi-Conservative Replication

Before a cell divides, its DNA must be copied accurately. Replication is semi-conservative: the two parent strands separate and each serves as a template for a new complementary strand, so every daughter molecule has one old and one new strand. Helicase unwinds the helix, primase lays down a short RNA primer, and DNA polymerase adds nucleotides to build the leading strand continuously and the lagging strand in short pieces.

Transcription and the Genetic Code

In transcription, RNA polymerase copies the information in the template strand of DNA into a single-stranded mRNA. In eukaryotes this first copy is processed: introns are removed by splicing, a cap is added at the 5' end and a poly-A tail at the 3' end. The mRNA is read three bases at a time, and each group of three is a codon. The genetic code is triplet, universal, non-overlapping, comma-less, unambiguous and degenerate. It works as the dictionary that converts a base sequence into an amino acid sequence.

Translation and Protein Assembly

Translation is the making of a protein on the ribosome, using the codons of mRNA as instructions. Transfer RNA is the adapter: each tRNA carries a specific amino acid and has an anticodon that pairs with the matching codon on the mRNA. The ribosome joins neighbouring amino acids by peptide bonds, and the growing polypeptide chain is released when a stop codon is reached, after which it folds into a working protein.

Gene Regulation and Genome Technologies

Cells do not keep every gene switched on all the time. In the lac operon of E. coli, the genes for digesting lactose are transcribed only when lactose, the inducer, is present; otherwise a repressor blocks them. On a much larger scale, scientists can now sequence entire genomes. The Human Genome Project mapped and sequenced human DNA, and DNA fingerprinting compares repeated DNA sequences to identify individuals, settle disputes over parentage and help in forensic work.

Common mistakes to avoid

• Mixing up the template strand and the coding strand. The template strand (3' to 5') is the one copied; the coding strand (5' to 3') has the same sequence as the mRNA, except that mRNA has uracil in place of thymine.
• Thinking DNA polymerase can start a new strand on its own. It can only add nucleotides to an existing 3'-OH end, so a short RNA primer is needed first.
• Assuming all 64 codons code for amino acids. Three of them, UAA, UAG and UGA, are stop codons and code for no amino acid.
• Assuming eukaryotic genes are continuous. They contain non-coding introns, which must be spliced out before the mRNA is used.
• Mixing up transcription and translation. Transcription copies DNA into RNA (in the nucleus in eukaryotes); translation uses mRNA to make protein on ribosomes in the cytoplasm. In bacteria, which have no nucleus, both happen in the cytoplasm.

Test yourself on these with the practice test, then check the worked reasoning in the solved MCQs.

Frequently asked questions

What is the difference between DNA and RNA?

DNA has deoxyribose sugar and the base thymine, and is usually double-stranded, which makes it stable and suited to long-term storage of genetic information. RNA has ribose sugar, which carries an extra hydroxyl group, and uracil in place of thymine. It is usually single-stranded, more reactive, and can act as a messenger or even a catalyst.

How did Hershey and Chase prove DNA is the genetic material?

They grew bacteriophages in two ways: one batch with radioactive phosphorus (32P), which labels DNA, and another with radioactive sulphur (35S), which labels protein. After infection, radioactive phosphorus was found inside the bacteria, while radioactive sulphur stayed outside with the empty coats. So DNA is what enters and carries the instructions.

What is semi-conservative replication?

When DNA replicates, its two strands separate and each acts as a template for a new complementary strand. Each of the two daughter molecules therefore keeps one original strand and gains one new strand. Meselson and Stahl confirmed this experimentally using heavy nitrogen (15N).

Why is the genetic code called degenerate?

There are 61 codons that code for amino acids but only 20 amino acids, so most amino acids have more than one codon. For example, several codons all specify leucine. Such codons usually differ in the third base, and the wobble in pairing at that position lets one tRNA read more than one codon.

What does transfer RNA do in translation?

tRNA is the adapter between the mRNA and the amino acids. One end, the amino acid acceptor end, carries a specific amino acid. The anticodon loop has three bases that pair with the matching codon on mRNA. This makes sure the right amino acid is added at each position in the chain.

How does the lac operon work?

When there is no lactose, the regulator gene makes a repressor protein that binds to the operator and stops RNA polymerase from transcribing the structural genes. When lactose is present, it acts as the inducer: it binds the repressor and changes its shape so it can no longer bind the operator. The genes are then transcribed and the enzymes for using lactose are made.

What is DNA fingerprinting used for?

DNA fingerprinting compares short DNA sequences repeated many times, called variable number tandem repeats (VNTRs). The number of repeats differs from person to person, so the band pattern is almost unique to each individual. It is used in forensic investigations, to settle paternity disputes, in wildlife conservation and in studying evolutionary relationships.