Manipulating Genomes Revision Notes for OCR A-Level Biology A

Uniqueness of DNA

DNA contains the genetic instructions for all living organisms, and whilst much of our DNA is shared with other humans and even other species, specific regions make each individual's DNA unique. This uniqueness forms the basis of DNA databases used in forensic science and identification.

DNA databases and individual identity

DNA held in forensic databases represents only a small portion of an individual's total genetic material. However, this sample is sufficient to uniquely identify a person, with the exception of identical twins who share the same DNA sequence.

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Although humans share the majority of their genome with each other and have significant DNA similarities with other species, certain regions show variation between individuals. These variable regions can be analysed to create a unique genetic profile.

This makes sense when we consider that humans use many of the same enzymes for fundamental processes such as respiration, and share developmental genes like homeobox genes with other eukaryotes.

DNA analysis techniques, combined with sophisticated data storage and retrieval systems, have transformed our ability to identify individuals and understand genetic diversity since the 1980s.

What is a genome?

The genome is the minimum quantity of genetic material that contains one complete set of all the genes of an individual, population, or species. In humans, this includes the DNA found in 22 autosomes (non-sex chromosomes), the X chromosome, the Y chromosome, and mitochondrial DNA. Plant genomes also include chloroplast DNA.

Genomics is the application of genetics and molecular biology techniques to map genes on chromosomes and determine the complete base sequence of genes or entire genomes.

Genome size and complexity

Genomes vary dramatically in size and complexity across different organisms. Since most genomes consist of double-stranded DNA, their size is measured in:

Base pairs (bp): individual paired nucleotides
Kilobase pairs (kbp): $10^3$ bp
Megabase pairs (Mbp): $10^6$ bp

Examples of genomes

Organism	Genome structure	Size	Number of genes
HIV (virus)	Single-stranded RNA	5000 bases	9
Escherichia coli (bacterium)	Single, circular double-stranded DNA	$5 \times 10^6$ bp	~4000
Mouse (Mus musculus)	Linear double-stranded DNA in 19 autosomes + X and Y chromosomes	$2.8 \times 10^9$ bp	~23000
Mouse mitochondrial genome	Circular double-stranded DNA	$16.3 \times 10^3$ bp	13 proteins + tRNA and rRNA genes
Human (Homo sapiens)	Linear double-stranded DNA in 22 autosomes + X and Y chromosomes	$3.0 \times 10^9$ bp	~21000
Human mitochondrial genome	Circular double-stranded DNA	$16.5 \times 10^3$ bp	Proteins + tRNA and rRNA genes

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This comparison reveals several key patterns:

Viral genomes are the simplest, containing minimal genetic information
Prokaryotic genomes are smaller and less complex than eukaryotic genomes
Interestingly, humans have only slightly more genes than mice (~21000 vs ~23000), despite our perceived complexity
Mitochondrial genomes are remarkably similar in size between mice and humans

Structure of eukaryotic genomes

Eukaryotic genomes contain several distinct types of DNA sequence, each with different functions.

Structural genes

Structural genes code for polypeptides by specifying the sequence of amino acids. Each structural gene contains:

Exons: coding sequences that are transcribed into mRNA and translated into protein
Introns: non-coding sequences that are transcribed but removed during mRNA processing before translation

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Worked Example: Human Haemoglobin β-polypeptide Gene

The gene coding for the β-polypeptide of human haemoglobin demonstrates the typical structure of a eukaryotic gene:

Total gene length: $1605$ bp

Exon composition:

Three exons with a combined length of $438$ bp
These code for a polypeptide of $146$ amino acids

Calculation: Since the genetic code is a triplet code:

$\text{Number of amino acids} = \frac{\text{Total exon length}}{\text{Codon size}} = \frac{438}{3} = 146 \text{ amino acids}$

Intron composition:

Remaining sequence: $1605 - 438 = 1167$ bp
This consists of two introns that are removed during mRNA processing

Regulatory genes

Regulatory genes control gene expression. Some regulatory genes code for proteins called transcription factors, which bind to DNA and influence whether a gene is transcribed. Others code for various forms of RNA that also control transcription.

Promoters

Promoters are control sequences located upstream (towards the 5' end) of genes. They serve as binding sites for RNA polymerase at the start of transcription. The presence and accessibility of promoters determines whether a gene can be transcribed.

Non-coding DNA

Long stretches of DNA separate structural and regulatory genes. Previously dismissed as "junk DNA", these regions are now understood to play roles in gene regulation and chromosome structure.

Organellar genomes

Eukaryotic genomes include DNA in organelles:

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Mitochondrial DNA (mtDNA): present in all eukaryotes, this circular double-stranded DNA resembles prokaryotic genomes with minimal non-coding sequences

Chloroplast DNA (ctDNA): present in plants and some protoctists, also circular and prokaryotic-like in structure

Both organellar genomes originated from ancient prokaryotes that were engulfed by early eukaryotic cells through endosymbiosis.

The Arabidopsis thaliana genome

Thale cress (Arabidopsis thaliana) serves as a model organism for plant genetics. It has a diploid number of $10$ chromosomes in the nucleus, plus DNA in chloroplasts and mitochondria.

The Arabidopsis genome structure demonstrates the typical organisation of a plant genome:

Genome component	Size (Mbp)	Number of genes
Nuclear chromosome I	29.1	6543
Nuclear chromosome II	19.6	4036
Nuclear chromosome III	23.2	5220
Nuclear chromosome IV	17.6	3825
Nuclear chromosome V	25.9	5874
Total nuclear genome	115.4	25498
Mitochondrion	0.37	58
Chloroplast	0.15	79

This table shows that the nuclear genome contains the vast majority of genes, whilst organellar genomes are much smaller. The variation in chromosome size reflects differences in the number of genes and amount of non-coding DNA each contains.

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Key Points to Remember:

The genome contains one complete set of all genes, including nuclear and organellar DNA in eukaryotes
Whilst humans share most DNA sequences with each other and other species, specific variable regions make each person's DNA unique (except identical twins)
Eukaryotic genomes contain structural genes (with exons and introns), regulatory genes, promoters, and non-coding DNA
Genome size is measured in base pairs (bp), kilobase pairs (kbp = $10^3$ bp), or megabase pairs (Mbp = $10^6$ bp)

Manipulating Genomes (OCR A-Level Biology A): Revision Notes