1.2 Functional Genomics Overview Flashcards
What is information?
Information is the result of processing,
manipulating and organizing data.
From 2-D DNA to 4-D phenotypes, is a DNA sequence data or information?
DNA is DATA, DNA is used by cells as cellular interactions demands and information is the result of processing and manipulating data
Cells gives rise to information, this is different to the way Crick thought of it.
DNA -> RNA -> Protein
Why
Because the DNA doesnt MAKE anything, without regulatory mechanisms, transcription factors and RNA polymerase.
Eukayotic promoters are made of activators and repressors, which function on…
Enhancers, and silencers
Data to information in space and time.
Cellular context
This ‘decision’ is affected by the context the cell finds itself in.
What is DATA?
A representation of facts, concepts, or instructions in a formalized manner suitable for communication, interpretation,
or processing by humans or by automated means.
TIME
Data to information in space
and time.
Step 2. ‘Decide’ which version to decode to a mature mRNA molecule
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
Decide’ which version to decode to a mature mRNA molecule
What happens to the version of muscle protein?
Version of a protein – e.g muscle protein – encoding a gene – original RNA – gets spliced depending on the context – translated into different proteins
Where is the information for the protein? Is it in the DNA?
Well hardly because it give rise to several things – it is incomplete!
One gene – one enzyme One gene – one polypeptide One gene – one RNA molecule One gene many RNA molecules ???????????????????
This decision is affected by the context the cell finds itself in.
What does the DNA do?
What does the protein do?
What does the cell do?
DATA is what the DNA does
FUNCTION is what the protein does
INFORMATION is what the cell does
Where is the unit of inheritance?
What does DNA represent?
DNA is DATA it has a molecular potential, but realization of this potential is context sensitive
RNA is a single stranded nucleic acid… it is the origins of…
Dimensions in biology, because you will not get a 4D system from DNA because DNA structure is too constrained
The RNA encoded from DNA is a single strand so it can…
fold in different ways, realizing the potential to go from linear array into a new structure - physical structure - which is what transfer RNA is.
RNA goes from a DIGITAL language and makes an
ANALOGUE language of proteins which has a subtle about them
ANALOGUE language, protein - changing the temperature
leads to changes - protein felxible
Complexity arises from modularity
- 4 bases
- 20 amino-acids
- 1000 protein folds
The genes are the same –
What changes over time and space?
it is how they are regulated that is different
Cellular differentiation
Differentiation of cells one fertilised eggs, from one single genome giving rise to complexity
Cellular differentiation
– as it goes through we end up with different types of cells
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
Mouse and Human genetic similarities
Mouse and Man
Man and Monkey – even more similar, the proteins are the same – its is the architecture of the protein
BEYOND THE GENE PARADIGM
DIMENSIONAL BIOLOGICAL
INFORMATION.
• 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.
- GENETIC DATA ARE INHERITED.
* BIOLOGICAL INFORMATION: THE MEANING GIVEN TO INHERITED DATA BY THE WAY IT IS INTERPRETED.
• THERE ARE DIFFERENT LEVELS OF BIOLOGICAL INFORMATION.
LEVELS OF 4-D BIOLOGICAL
INFORMATION.
Simple biological information such as
SIMPLE BIOLOGICAL INFORMATION.
e.g Polypeptides.
• HIGHER ORDER BIOLOGICAL
INFORMATION.
• E.g. Protein Complexes, biochemical
pathways, transposon systems,
chromosomes, cells, organisms.
COMBINATORIAL STRATEGY
FOR CREATING DIVERSITY
Simple changes in the expression of one or two proteins can give you a change in expression in the end
ENCODE: Encyclopaedia Of DNA
Elements
By the numbers
- 10 years.
- 442 scientists.
- 147 different types of HUMAN cells.
- 24 different types of experimental assays.
What was ENCODE?
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.
Linear relationship between
Example
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
ENCODE HAS ALREADY
DISCOVERED THAT…
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.
THE GENOME HAS A COMPLEX
BIOLOGICALY RELEVANT 3-D
ARCHITECTURE.
1,000 sequences were switches in one part
of the genome which were physically
reaching over and controlling the activity of
a distant gene.
A WORD OF CAUTION…
• ENCODE suggests that 80% of the Human
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.
