1.2 Functional Genomics Overview

Question 1

What is information?

Answer 1

Information is the result of processing,

manipulating and organizing data.

Question 2

From 2-D DNA to 4-D phenotypes, is a DNA sequence data or information?

Answer 2

DNA is DATA, DNA is used by cells as cellular interactions demands and information is the result of processing and manipulating data

Question 3

Cells gives rise to information, this is different to the way Crick thought of it.

DNA -> RNA -> Protein

Why

Answer 3

Because the DNA doesnt MAKE anything, without regulatory mechanisms, transcription factors and RNA polymerase.

Question 4

Eukayotic promoters are made of activators and repressors, which function on…

Answer 4

Enhancers, and silencers

Question 5

Data to information in space and time.

Cellular context

Answer 5

This ‘decision’ is affected by the context the cell finds itself in.

Question 6

What is DATA?

Answer 6

A representation of facts, concepts, or instructions in a formalized manner suitable for communication, interpretation,
or processing by humans or by automated means.

Question 7

TIME

Data to information in space
and time.
Step 2. ‘Decide’ which version to decode to a mature mRNA molecule

Answer 7

Change the timing of change, will lead to a change of outcome of that cell

E.g

Phag lamda,

Lamda invades E. coli, it either integrates or lyses it - and which of these happens is the outcome of a molecular race between the repressor protein

Molecular races

Question 8

Decide’ which version to decode to a mature mRNA molecule

What happens to the version of muscle protein?

Answer 8

Version of a protein – e.g muscle protein – encoding a gene – original RNA – gets spliced depending on the context – translated into different proteins

Question 9

Where is the information for the protein? Is it in the DNA?

Answer 9

Well hardly because it give rise to several things – it is incomplete!

Question 10

One gene – one enzyme 
One gene – one polypeptide 
One gene – one RNA molecule 
One gene many RNA molecules 
???????????????????

Answer 10

This decision is affected by the context the cell finds itself in.

Question 11

What does the DNA do?
What does the protein do?
What does the cell do?

Answer 11

DATA is what the DNA does
FUNCTION is what the protein does
INFORMATION is what the cell does

Question 12

Where is the unit of inheritance?

What does DNA represent?

Answer 12

DNA is DATA it has a molecular potential, but realization of this potential is context sensitive

Question 13

RNA is a single stranded nucleic acid… it is the origins of…

Answer 13

Dimensions in biology, because you will not get a 4D system from DNA because DNA structure is too constrained

Question 14

The RNA encoded from DNA is a single strand so it can…

Answer 14

fold in different ways, realizing the potential to go from linear array into a new structure - physical structure - which is what transfer RNA is.

Question 15

RNA goes from a DIGITAL language and makes an

Answer 15

ANALOGUE language of proteins which has a subtle about them

Question 16

ANALOGUE language, protein - changing the temperature

Answer 16

leads to changes - protein felxible

Question 17

Complexity arises from modularity

Answer 17

• 4 bases
• 20 amino-acids
• 1000 protein folds

Question 18

The genes are the same –

What changes over time and space?

Answer 18

it is how they are regulated that is different

Question 19

Cellular differentiation

Answer 19

Differentiation of cells one fertilised eggs, from one single genome giving rise to complexity

Question 20

Cellular differentiation

– as it goes through we end up with different types of cells

Answer 20

Look at the outcome – its completely different – where is the information? It is not in the DNA it has arisen in space and time as they divide and have cellular memory – things that change the histones around the DNA – histones are tightly packed around it

Question 21

Mouse and Human genetic similarities

Mouse and Man

Answer 21

Man and Monkey – even more similar, the proteins are the same – its is the architecture of the protein

Question 22

BEYOND THE GENE PARADIGM

DIMENSIONAL BIOLOGICAL
INFORMATION.

Answer 22

• GENETIC INFORMATION IS NOT INHERITED!
• INFORMATION: THE MEANING
GIVEN TO DATA BY THE WAY IT IS INTERPRETED.
• INFORMATION REQUIRES A CONTEXT IN ORDER TO EXIST.

Question 23

• GENETIC DATA ARE INHERITED.

* BIOLOGICAL INFORMATION: THE MEANING GIVEN TO INHERITED DATA BY THE WAY IT IS INTERPRETED.

Answer 23

• THERE ARE DIFFERENT LEVELS OF BIOLOGICAL INFORMATION.

Question 24

LEVELS OF 4-D BIOLOGICAL
INFORMATION.

Simple biological information such as

Answer 24

SIMPLE BIOLOGICAL INFORMATION.

e.g Polypeptides.

Question 25

• HIGHER ORDER BIOLOGICAL

INFORMATION.

Answer 25

• E.g. Protein Complexes, biochemical
pathways, transposon systems,
chromosomes, cells, organisms.

Question 26

COMBINATORIAL STRATEGY

FOR CREATING DIVERSITY

Answer 26

Simple changes in the expression of one or two proteins can give you a change in expression in the end

Question 27

ENCODE: Encyclopaedia Of DNA
Elements

By the numbers

Answer 27

• 10 years.
• 442 scientists.
• 147 different types of HUMAN cells.
• 24 different types of experimental assays.

Question 28

What was ENCODE?

Answer 28

A catalogue of ANY biochemical
activity associated with each
nucleotide in the human genome

• Map RNA transcripts, binding sites for
transcription factors and chromosomal
proteins.
• Identify all protein-coding genes.
• Identify promoters and enhancers with
transfection of reporter constructs into cell
lines.

Question 29

Linear relationship between

Example

Answer 29

DNA and phenotype is exceptional

Example: Sickle cell anemia, you can look at the DNA and see the relationship - but it is an exception

Linear

most things are complex

Heart disease - cancer - are multifactorial

Question 30

ENCODE HAS ALREADY

DISCOVERED THAT…

Answer 30

Disease-associated SNPs are 60 percent of
more likely to lie within functional, noncoding
regions, especially in promoters and
enhancers.
The team found five SNPs associated with
Crohn’s disease, a type of bowel disorder.
that interacted with a specific type of
transciption factor.

Question 31

THE GENOME HAS A COMPLEX
BIOLOGICALY RELEVANT 3-D
ARCHITECTURE.

Answer 31

1,000 sequences were switches in one part
of the genome which were physically
reaching over and controlling the activity of
a distant gene.

Question 32

A WORD OF CAUTION…

• ENCODE suggests that 80% of the Human

Answer 32

Genome is functional.
• How do we define ‘function’, especially in light
of the fact that current estimates of the
fraction of the genome evolutionarily
conserved by purifying selection is 10%.

See Graur et al Genome Biol Evol 5(3): 578-
590.