Genomics and Proteomics
Introduction
The completion of the human genome sequencing project in 2002 has created large interest in genetics as we all try to get a better understanding of what genes are and how they function. Most of us are aware that genes are the basic units of heredity and encode the information to produce proteins (see below Figure 1), which carry out most life functions and make up the majority of cellular structures.
Figure 1: From gene to protein (source: US Department of Energy)
In the past we believed that each of the many genes in an organism codes for one specific protein. We now understand that the level of complexity is greatly increased when we look at proteins: an individual gene may encode many distinct proteins. For a complex organism like a mammal, it is important to look at all genes and proteins, understand how they are controlled and interact and recognise how variants for these genes are responsible for the variability we see in populations (eg in humans - different eye, skin and hair colours).
Genomics is the study of the genome!
The genome is an organism's complete set of deoxyribonucleic acid (DNA). Each cell in a mammal (except mature red blood cells) contains a full copy of the genome. The length of the genome is measured in base pairs (bp) and differs widely between different species (Table1). Genomics looks at all the genes as a dynamic system, over time, to determine how they interact.
|
Organism |
Number of chromosomes |
Genome size in base pairs |
Number of predicted genes |
Part of the genome that encodes proteins |
|
Bacteria |
1 |
~400,000 - ~10,000,000 |
5000 |
90% |
|
Yeast |
12 |
14,000,000 |
6000 |
70% |
|
Worm |
6 |
100,000,000 |
18,000 |
27% |
|
Fly |
4 |
300,000,000 |
14,000 |
20% |
|
Weed |
5 |
125,000,000 |
25,500 |
20% |
|
Human |
23 |
3,000,000,000 |
30,000 |
< 5% |
|
Cattle |
30 |
3,000,000,000 |
30,000 |
<5% |
Table 1: The total genome size and the number of predicted proteins differ considerably in different species (source: European Bioinformatics Institute, http://www.ebi.ac.uk)
In genomics we attempt to determine all nucleotide sequences encoding and regulating the expression of genes within a species and recognise all nucleotide sequence variants responsible for genetic variation between individuals. The sequencing of mammalian genomes is occurring at an increasing rate with human, mouse and rat sequences already completed. Several economically important species like the cow are currently being sequenced.
Proteomics is the study of the proteome!
In 1994, Australian scientist Marc Wilkins invented the term 'proteomics' which he defined as the 'attempt of describing the composition of all proteins in a qualitative and quantitative manner present within one entity (cell, tissue, body fluid, organism) at specified physiological states and time points.' (pictured right: gel electrophoresis: a process used to separate proteins)This definition highlights already that the proteome might be much more complex than the genome - cells in different tissues or at different time points contain different proteomes, whereas the genome is the same in all cells of an individual. In contrast to DNA, proteins are exposed to greater modulation affecting their expression within the cellular environment.
Multiple regulatory switches control genes, the existence of alternative transcripts for most genes and post-translational modifications are some of the reasons why an individual gene may be activated at different times or in different tissues to encode many distinct proteins.
Therefore, any investigation of a proteome must not only take into account the proteins function, but also their ongoing modification and regulation and will ultimately lead to the identification of protein-protein interactions, organelle composition, protein activity patterns and protein profiles (pictured right: proteomics data from gel electrophoresis).
How do we use genomics and proteomics in the Dairy CRC?
Ultimately genomics and proteomics will help to provide an important part of the answer to a basic question in biology: Why is an organism the way it is and different from other organisms? The availability of sequence information and the understanding of why specific proteins are present in cells at specific times will greatly improve our understanding of how organisms function. This has important consequences for improving human health, and for animal productivity and welfare.
Within the Dairy CRC our main interest is the identification and detailed  characterisation of specific genes and proteins associated with lactation in the dairy cow (see Functional Genomics).
For more information on the Human Genome Project, visit the US Department of Energy Office of Science http://doegenomes.org
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