LECTURE 1 - GENOMES ORGANISATION

A genome is a collection of DNA molecules characteristic of an organism.

All organisms have evolved from a common ancestor and therefore have genomic
aspects in common. C-value is the quantity of unique genetic material in an organism.
- There is generally a rough correlation between a c-value and the complexity of
an organism.
- The number of genes roughly parallels complexity
- There are numerous exceptions to this c-value paradox.
We have discovered a lot about genomes by studying model organisms, we know that
essentially all genomes are very similarly. Aspects of genome organization may differ
between organisms.
The genome in prokaryotes is in the genetic material (nucleoid) and the DNA in
eukaryotes is in the nucleolus and in the mitochondrial genome.
Eukaryotic chromosomes are made of equal amounts of protein and DNA.
Chromosomes are highly condensed during mitosis (Heterochromatic) but must be
relaxed to be expressed in the inter-phase (Euchromatic).
The chromosome structure has two fundamental roles:
- To ensure appropriate, tissue specific gene-expression
- To ensure accurate transmission of genetic material between generations.

Chromosomal Variety:
- Ploidy: number of sets of chromosomes in a cell
- Diploid: two copies of each chromosome, homologous, 2n (somatic cells)
- Haploid: a single copy of each chromosome (germ cells)
Many eukaryotes also may have more than two copies of each chromosome and are
polyploidy. This is commonly found in plants.
DNA is not just found in the nucleus in eukaryotes.
Eukaryotic genomes are not restricted to the nucleus. Mitochondria and Chloroplast
genomes:
- Mitochondria convert organic molecules into energy by aerobic metabolism.
- Chloroplasts use energy from sunlight to sythesises organic material from water
and carbon dioxide (photosynthesis)
à Both are likely derived from prokaryotic cells that established symbiotic relationship
with lost cells. Mitochondria and chloroplasts contain their own genomes.
à Both mitochondria and chloroplast DNA are circular. The number of mitochondria
contained with a cell can be important in certain diseases. There are known mutations
in mitochondria.
- Cells can contain multiple copies of these organelles.

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 o Organelle number varies between cells and tissues of different
eukaryotes.
- Each organelle also contains multiple circular DNA molecules.
- Most mitochondrial genes function solely within the mitochondria.
o Nuclear gene products may be imported to augment or facilitate
function.
- Development of a functional chloroplast depends on expression of both nuclear
and cpDNA.

What makes a genome:

Genomes are made of DNA, RNA, repetitive sequence and intronic sequences.
Organisation also varies within and between chromosomes. The human genome has on
average of 1 gene every 100kb (in practice, range is 0-64 genes per 100kb).

Genome Organisation
Protein coding genes vary between and within species; they show an enormous
variation in size and internal organisation.
- In simple organisms such as bacteria, genes are usually very short (∼1kb)
- In complex eukaryotes, genes show a huge variation in size.
Organisation of protein coding genesis is often linked to function.
- Operons: in prokaryotic genomes, genes with related functions may be located
close together in the order in which encoded proteins are required for particular
metabolic reactions.
o LAC Operon à set of genes required to regulate lactose utilisation in E.
coli.
It is a set of contiguous structural genes that transports lactose into cells
where it is cleaved to glucose and galactose.
Regulated by two controlling elements – repressor gene (I) encodes a
repressor which binds to operator (O) under appropriate conditions and
stops transcription.
If there is no lactose or allolactose, the inducer mRNA is transcribed,
which binds to the repressor and prevents transcription of the LAC
operon.

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 If there is lactose, the lactose binds to the repressor, which means it can’t
bind to the operator; and there is a transcription and translation of lac
structural genes.

- Gene Cluster (for example, globin genes): occurs in both prokaryotes and
eukaryotes. Some protein coding genes and other chromosomal elements
exhibit a level of organisation.
o Eukaryotic coding gene organisation – Globin genes: on an evolutionary
timescale gene duplication has led to multiple copies of some genes.
There is such number variation that has led to the existence of gene
families. There are other clustered gene families such as growth hormone
gene cluster, HOX genes, Histone gene family, etc.
Human globin genes are arranged in two clusters on two separate
chromosomes: alpha globin and beta globin.
Beta globin genes/proteins are involved in binding or transporting oxygen.

Humans have less genes than expected. 10-20% non-coding genome has a functional
role.
Repetitive DNA:
- There is not much repetitive DNA in prokaryotic genomes
o ∼11% of the E. coli genome consists of non-transcribed regions.
- Repetitive DNA contributes significantly to the large genome sizes of eukaryotes
(particularly to large genomes of certain plants and amphibians)
- 30% repetitive DNA in the yeast genome
- 50% in the human genome
Tandem repeats:
o There are three classes of tandem repeats, named depending on their
size.

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 o Satellite DNA repeats are often associated with centromeric regions of
the genome. One of the biggest satellites (up to 100kb)
o Minisatellite DNA repeats primarily associated with telomeric locations
(up to 20kb)
o Microsatellite DNA repeats are widely distributed in euchromatin
(<100bp)
*foto*

Transposons derived repeats:

o Transposons derived repeats are organised in an interspersed fashion
throughout the genome
o Vast majority of transposons and transposon-derived sequences can no
longer transpose.
o Two classes of transposons – depending on how the transposon moves
(transposes)
§ DNA transposons
§ Retrotransposons (includes LINEs and SINEs)