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Lecture notes MCB2020F - Eukaryotic genome organisation, Extra-nuclear inheritance and Evolutionary genetics.

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In Eukaryotic genome organisation we will cover how DNA is compacted into chromosomes and how this affects gene function. We will examine chromosomal re-arrangements and changes in chromosomal number and see how this can affects the phenotype of an organism. In Extra-nuclear inheritance we will look at genome organisation in mitochondria and chloroplasts, the origin of extra-nuclear DNA, mitochondrial DNA inheritance and mitochondrial diseases. In Evolutionary genetics we will see how mitochondrial DNA is used as a population marker and how it aided our understanding of human evolution. We will examine how the frequency of alleles changes in a population under Hardy-Weinberg equilibrium, and consider random genetic drift, inbreeding and selection.

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L1 - Chromatin Structure
Eukaryotic Gene Regulation
What is a chromosome
The chromosome is called a chromosome because it contains DNA and protein,
which together is called chromatin.

Chromatin consists of 1/3 DNA; 1/3 histone
proteins; 1/3 non-histone protein

The reason DNA is packaged, or compacted tightly into a chromosome, is
because the human genome, for example, is three times ten to the nine base
pairs, or it is three billion base pairs. Which, stretched out, would be as long as
two metres, but has to be packaged in order to fit into the nucleus. That’s one of
the reasons.


Histone Proteins
So, what are these non-DNA parts of chromatin, the protein parts?

The first part’s called the histone proteins.

Histone proteins are made up of amino acids that are mostly small, basic,
positively-charged amino acids.

These amino acids are lysine and arginine, which together make up half of the
chromatin proteins by weight.

These amino acids have a positive charge due to the presence of lysine and
arginine, which allows them to bind and neutralise DNA, which has a slightly
negative charge.

So you have a tight binding of histones to DNA. There are a number of different
kinds of histones and they have very cryptic names. There are five types of
histones.




L1 - Chromatin Structure 1

, They’re called histone H1, histone H2A, histone H2B, histone H3 and histone 4.
And these histones, these five kinds of histones, have two basic functions.

The first function is some of those histones combine together to form the core
histones, which form the nucleosome.

So the nucleosome is made up of core histones, which are all the above-
mentioned histones except H1 is not part of the core histones which form the
nucleosome.

Instead, H1 is outside the nucleosome and the two nucleosomes are joined
together by the linker histone → H1.

Very important to note is that histone proteins are highly conserved. So what we
say is, is that there’s a high level of sequence conservation of histone proteins
among diverse organisms. What that means is that the histone protein amino
acid sequence would be the same, or incredibly similar, between, let’s say for
example, a plant and an animal.

If we looked at histone H4, the amino acid sequence of histone H4 between a
pea plant and an animal like a cow, there is 102 amino acids in histone H4. And
of the 102 amino acids, all except two are the same. That is to say, there are
only two amino acids different between a plant and an animal, for histone H4.
And any sequence that has a high degree of conservation, is normally correlated
and gives us insight into the absolutely important function of that DNA or that
protein sequence. And therefore, histones are fundamental to life, because you
have to package DNA and histones to make chromosomes, and without histones
you can’t make chromosomes. And therefore histone sequences are incredibly
conserved.


Non-histone Proteins
There’s a large variety of different kinds of non-histone proteins.

There are hundreds to thousands to millions of different types of non-histone
proteins.

Given the fact that we have so many different kinds of non-histone proteins, we
have a large variety of functions performed by these proteins.

The first set of proteins are scaffolding or structural proteins that aid the
compaction of chromosomes. So packed scaffold proteins are part of the
backbone of what makes up chromosomes.




L1 - Chromatin Structure 2

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Colleen o\'ryan
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