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Genetics and evolution · Hereditary material

DNA and RNA

Before you start, make sure you know: Types of cells: prokaryotic and eukaryotic (1st Year, Junior Cycle)

In the nucleus of each of your cells there are about two metres of DNA divided into 46 molecules, coiled up so tightly that they fit into a space of just a few micrometres: deoxyribonucleic acid, DNA. Since Hershey and Chase's experiment in 1952 we have known for certain that it is this molecule, and not proteins, that carries hereditary information. This section studies its chemical composition, its three-dimensional geometry, how it copies itself and how it is compacted to fit inside the nucleus.

Nucleotides: the chemical unit of DNA

Chemical analysis of DNA reveals that it is made up of just three ingredients: phosphoric acid, a simple sugar and four nitrogenous substances. How do these few pieces assemble to encode all the characteristics of a living thing?

A DNA nucleotide, with its phosphate group, deoxyribose and a nitrogenous base, and a chain of three nucleotides (A, T and G) joined by phosphodiester bonds forming the sugar-phosphate backbone. Purine bases, with a double ring, can be distinguished from pyrimidine bases, with a single ring. one nucleotide P phosphate group O 5' 3' deoxyribose nitrogenous base (e.g. adenine) purines (A, G) double ring pyrimidines (T, C) single ring chain of nucleotides sugar-phosphate backbone P P P A (adenine) T (thymine) G (guanine) 5' 3' bond phosphodiester
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Explain what DNA is, what type of information it contains, and in which part of a eukaryotic cell most of this molecule is found.

Explain what DNA is, what type of information it contains, and in which part of a eukaryotic cell most of this molecule is found.

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Explain what a nucleotide is and name its three components. Which of them varies from one nucleotide to another and constitutes the "letter" of genetic information?

Explain what a nucleotide is and name its three components. Which of them varies from one nucleotide to another and constitutes the "letter" of genetic information?

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The DNA double helix resembles a spiral staircase. Explain which molecules form the "sides" of the staircase and which form the "rungs", and how the components of each…

The DNA double helix resembles a spiral staircase. Explain which molecules form the "sides" of the staircase and which form the "rungs", and how the components of each rung are joined together.

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The double helix and Chargaff's rule

The double helix was worked out in 1953 by James Watson and Francis Crick, using X-ray images taken by Rosalind Franklin. It is a good example of how scientists build on each other's evidence.

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Name the four nitrogenous bases of DNA and explain the base-pairing rule followed by the double helix.

Name the four nitrogenous bases of DNA and explain the base-pairing rule followed by the double helix.

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The diagram shows a segment of a DNA double helix. State what markers 1 and 2 represent, and complete the missing bases on the rungs marked with ?, knowing that A always…

The diagram shows a segment of a DNA double helix. State what markers 1 and 2 represent, and complete the missing bases on the rungs marked with ?, knowing that A always pairs with T and G with C.

A T G C G A T A C G C ? ? ? 1 2
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In the DNA of a species, $22\ \%$ of the bases are thymine. Calculate the percentage of adenine, guanine and cytosine, and explain your reasoning.

In the DNA of a species, $22\ \%$ of the bases are thymine. Calculate the percentage of adenine, guanine and cytosine, and explain your reasoning.

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The two strands of DNA are antiparallel: one runs along the double helix in the 5' to 3' direction and the other in the 3' to 5' direction. Explain with an analogy what…

The two strands of DNA are antiparallel: one runs along the double helix in the 5' to 3' direction and the other in the 3' to 5' direction. Explain with an analogy what it means for them to be antiparallel and what the 5' and 3' marks indicate.

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In a DNA molecule, $18\ \%$ of the bases are guanine. Calculate the percentages of cytosine, adenine and thymine, and explain each step of your reasoning.

In a DNA molecule, $18\ \%$ of the bases are guanine. Calculate the percentages of cytosine, adenine and thymine, and explain each step of your reasoning.

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A DNA strand has the sequence 5'-ATG CCG TTA-3'. Write the sequence of the complementary strand, also indicating its direction, and explain what you took into account.

A DNA strand has the sequence 5'-ATG CCG TTA-3'. Write the sequence of the complementary strand, also indicating its direction, and explain what you took into account.

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An astrobiology team analyzes the genetic material of an extraterrestrial microorganism. They discover that it consists of two facing strands, but they observe two…

An astrobiology team analyzes the genetic material of an extraterrestrial microorganism. They discover that it consists of two facing strands, but they observe two anomalies compared to terrestrial DNA: 1) the diameter of the double helix is not constant, but instead shows continuous widenings and narrowings; 2) both strands run in the same direction (both in the $5' \to 3'$ direction). Using the principles of purine/pyrimidine base complementarity and antiparallelism proposed by Watson and Crick, reason what type of chemical pairings would be causing these thickness irregularities and predict what physical or enzymatic difficulty a parallel double helix would present during cellular replication.

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A laboratory analyzes the nitrogenous base composition of the genetic material extracted from three different viruses, obtaining the following results: Virus 1: $30\ \%$…

A laboratory analyzes the nitrogenous base composition of the genetic material extracted from three different viruses, obtaining the following results:

  • Virus 1: $30\ \%$ adenine, $30\ \%$ thymine, $20\ \%$ guanine, $20\ \%$ cytosine.

  • Virus 2: $30\ \%$ adenine, $20\ \%$ thymine, $22\ \%$ guanine, $28\ \%$ cytosine.

  • Virus 3: $30\ \%$ adenine, $30\ \%$ uracil, $20\ \%$ guanine, $20\ \%$ cytosine.

Determine with reasoning for each virus: what type of nucleic acid it possesses (DNA or RNA) and whether its strand is single-stranded or double-stranded. Furthermore, justify why virus 2 does not contradict the laws of chemistry even though its percentages of adenine and thymine do not match.

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The double-stranded DNA of two bacterial species is analyzed: species A comes from a deep-sea hydrothermal vent at $85\ ^\circ\text{C}$ and species B comes from soil at…

The double-stranded DNA of two bacterial species is analyzed: species A comes from a deep-sea hydrothermal vent at $85\ ^\circ\text{C}$ and species B comes from soil at $20\ ^\circ\text{C}$. The analyses show that one of the samples contains $38\ \%$ cytosine and the other contains $19\ \%$ cytosine.

  1. a) Deduce and justify which percentage corresponds to each bacterium, based on the molecular stability of the bonds between base pairs.
  2. b) Calculate the percentage of all the other nitrogenous bases (adenine, thymine, and guanine) present in the DNA of the thermophilic bacterium in the sample.
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Certain cancer chemotherapy drugs (crosslinking agents) can covalently link the two strands of DNA. Imagine a hypothetical drug that acts by forming permanent covalent…

Certain cancer chemotherapy drugs (crosslinking agents) can covalently link the two strands of DNA. Imagine a hypothetical drug that acts by forming permanent covalent bonds between opposing nitrogenous bases of the double helix, replacing the usual hydrogen bonds.

  1. a) Predict why this drug suddenly halts the division of tumor cells, explaining which enzymes and processes of replication or transcription are physically prevented.
  2. b) Based on the case above, justify why biological selection maintained weak bonds (hydrogen bonds) between the two strands and strong bonds (covalent phosphodiester bonds) along each strand throughout evolution, instead of using only strong bonds or only weak bonds.
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In the historic Hershey and Chase experiment (1952) with bacteriophages: a) Predict what results would have been obtained in the bacterial pellet and in the supernatant…

In the historic Hershey and Chase experiment (1952) with bacteriophages:

  1. a) Predict what results would have been obtained in the bacterial pellet and in the supernatant liquid if the prevailing hypothesis of the time (that proteins constituted the hereditary material) had been correct.
  2. b) Imagine that a student proposes repeating the experiment by labeling the viruses with nitrogen-15 ($^{15}\text{N}$, a stable isotope) instead of using phosphorus ($^{32}\text{P}$) and sulfur ($^{35}\text{S}$). Justify why this experimental design would be completely useless for determining whether the genetic material is DNA or protein.
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Semi-conservative replication

Animation of the semi-conservative replication of DNA: the two original strands separate and a new green strand grows from left to right alongside each one, so that each daughter molecule has one old and one new strand original DNA (2 strands) copy 1: 1 old + 1 new copy 2: 1 old + 1 new
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Before dividing, the cell copies all of its DNA through replication. Explain what this process consists of and why it is said to be semi-conservative: which strands form…

Before dividing, the cell copies all of its DNA through replication. Explain what this process consists of and why it is said to be semi-conservative: which strands form each daughter DNA molecule and what role complementary base pairing plays in making an exact copy.

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DNA replication occurs before the cell divides by mitosis. Explain why it is essential that it happens in that order and what would happen to the genetic information of…

DNA replication occurs before the cell divides by mitosis. Explain why it is essential that it happens in that order and what would happen to the genetic information of the daughter cells if a cell divided without having copied its DNA first.

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The uninterrupted coding region of a eukaryotic gene consists of exactly $900$ base pairs (including the final stop codon). a) Calculate how many amino acids will make…

The uninterrupted coding region of a eukaryotic gene consists of exactly $900$ base pairs (including the final stop codon).

  1. a) Calculate how many amino acids will make up the protein translated from this gene.
  2. b) Suppose an insertion mutation of a single nucleotide occurs at position number $301$. Predict what consequences this mutation will have on the final length of the amino acid chain and on its biological function, compared to a point substitution mutation at that same position $301$. Justify your prediction using the concepts of reading frame and premature stop codon.
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DNA packaging: chromatin and chromosomes

If you unwind the DNA of a single human cell it measures about two metres, yet it has to fit inside a nucleus that is barely $6\ \mu\text{m}$ in diameter. How does the cell manage to fold that thread without it breaking or forming knots that are impossible to undo?

Levels of DNA packaging from top to bottom: the double helix coils around histones forming nucleosomes, these fold and supercoil into the chromatin fibre, and in cell division the chromatin condenses into a chromosome double helix of DNA coils around histones histones DNA nucleosomes (DNA + histones) fold and supercoil chromatin folded nucleosomes and supercoiled condenses to the maximum chromosome condensed (cell division)
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Order these structures from smallest to largest and explain in one sentence what each one is: chromosome, cell, gene, nucleotide, nucleus.

Order these structures from smallest to largest and explain in one sentence what each one is: chromosome, cell, gene, nucleotide, nucleus.

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Compare how DNA is organised in a bacterium and in a eukaryotic cell: where it is found, how many chromosomes there usually are and what shape they have.

Compare how DNA is organised in a bacterium and in a eukaryotic cell: where it is found, how many chromosomes there usually are and what shape they have.

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In a laboratory, an experimental drug is tested on a cell culture. The compound binds irreversibly to histones, preventing the DNA from unwinding from the nucleosomes.…

In a laboratory, an experimental drug is tested on a cell culture. The compound binds irreversibly to histones, preventing the DNA from unwinding from the nucleosomes.

  1. a) Predict which two molecular processes essential for the cell will be immediately blocked and justify why at the molecular level.
  2. b) If an already replicated cell enters mitosis and manages to condense its chromosomes, but the drug prevents it from decondensing them at the end of telophase, what consequences will this have for the viability of the daughter cells during interphase?
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A human metaphase chromosome measures about $5\ \mu\text{m}$, but the DNA strand it houses would measure about $5\ \text{cm}$ when stretched out (a $10\,000$-fold…

A human metaphase chromosome measures about $5\ \mu\text{m}$, but the DNA strand it houses would measure about $5\ \text{cm}$ when stretched out (a $10\,000$-fold packaging).

  1. a) If you apply an inhibitor of the enzyme RNA polymerase (responsible for transcription) to a cell in metaphase, you will see that it has barely any effect because RNA synthesis is already halted naturally. Justify this fact by relating it to the degree of chromatin compaction.
  2. b) Explain why it is essential for the cell to achieve such a level of packaging during mitosis, and why it would be lethal for it to maintain that same degree of condensation permanently during interphase.
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RNA, the helper of DNA

Comparison between DNA, a double helix of two strands with deoxyribose and bases A, T, G and C, and RNA, a single chain of nucleotides with ribose and bases A, U, G and C DNA Double-stranded (2 strands) Sugar: deoxyribose Bases: A, T, G, C nucleotide RNA Single-stranded (1 strand) Sugar: ribose Bases: A, U, G, C A adenine T thymine G guanine C cytosine U uracil Thymine (T) appears only in DNA; uracil (U) only in RNA.
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State three differences between DNA and RNA: the sugar they contain, the number of strands and one of their nitrogenous bases.

State three differences between DNA and RNA: the sugar they contain, the number of strands and one of their nitrogenous bases.

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Explain what a gene is and describe its relationship with DNA, chromosomes and proteins.

Explain what a gene is and describe its relationship with DNA, chromosomes and proteins.

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For decades, the hereditary material was thought to be proteins rather than DNA. Reason which three properties any molecule must fulfil in order to be the hereditary…

For decades, the hereditary material was thought to be proteins rather than DNA. Reason which three properties any molecule must fulfil in order to be the hereditary material and explain why DNA fulfils them.

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Back to the beginning: Think of a very long thread wound onto a tiny bobbin: the two metres of DNA fit inside a microscopic nucleus thanks to their progressive coiling and folding into chromatin, and during cell division they condense into chromosomes about $10{,}000$ times shorter than the stretched DNA.

Summary

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