Proteome and Genome
Genes are the blueprints for proteins. Roughly speaking, genes (DNA) make RNA, and RNA makes proteins.
The Human Genome Project mapped the human genome, and now genomes for many other species have been mapped.
To a first approximation, each gene makes one protein. If you know the genome for a species, then, you know all its proteins. That is, you can predict the amino acid sequence of each protein.
Only about one-third of the human proteins predicted by genomics have been isolated and studied. Proteomics is not limited to these well-studied proteins, but also deals with the predicted but as-yet-unstudied proteins.
Proteome Over Time
The genome of an organism — its DNA — never changes. In contrast, the proteome changes all the time. The amount of each individual protein varies constantly.
Protein levels present problems similar to the word problems of grade school arithmetic. Imagine two bathtubs that are filling and draining at the same time:
The upper tub is RNA. It fills when the gene is turned on so that its DNA makes RNA. It drains as the RNA makes proteins.
The lower tub is the protein, which is filled when the RNA makes protein. This tub is drained as the protein degrades.
The amount of protein therefore depends on how open each of the three faucets is. To make things more interesting, within living cells these faucets are continuously and independently adjusted.
Also, as the diagram below shows, neither the existence of a DNA gene, nor the measured levels of RNA corresponds to measured levels of the protein it makes. The gene is turned on at time zero, and RNA builds up. Later, the protein level starts to rise. It may stay high long after the RNA levels fall.
- The study of DNA, the genome, is genomics. DNA in a cell stays constant over time.
- The study of RNA is functional genomics (or transcriptomics), often referred to by its principle tool - microarrays. RNA levels rise and fall as genes are turned on an off.
- The study of proteins, the proteome, is proteomics. Protein levels rise and fall but lag RNA levels.
Proteome and Proteins
How many proteins are in the proteome? Because the human geneome has about 20,000 genes, you might guess that the human proteome has about 20,000 proteins. But this number is both too big and too small.
Why too small? The classic dogma of genetics is: one gene equals one protein. This is oversimplified; in fact, there are more proteins than genes.
Why too big? We usually consider the proteome at the level of only one specific organ or body fluid. A human brain cell and a human liver cell each have the same genome of 20,000 genes, but they have very different proteomes, each with only a subset of all possible human proteins.
Each of these points is discussed in more detail below.
Too Small
- Genes are made in sections called exons, which can be spliced together in different ways. About half of all human genes have an alternative splicing, with each splice variant corresponding to a different protein.
- Proteins are modified after they are made. Frequently, the proto-protein made from the gene is cut into sections to form many proteins with different properties. For example, the gene CO3_HUMAN can be spliced to form the proteins C3 beta, anaphylatoxin, C3c, C3d, C3f, and C3g — each with different properties and functions.
Too Big
Each tissue or bodily fluid has its own proteome. The human body has many proteomes - those for the blood, liver, brain, and so on. Furthermore, each organ has many types of cells: the brain has various types of neurons and glial cells as well as blood vessels and blood cells. Each cell type has its own proteome. Each of these proteomes have only a small fraction of all the possible proteins.
Let's look at one proteome — that of blood plasma.
Plasma Proteome
Plasma is blood without the red and white blood cells. One of the best studied proteomes is that of human blood plasma.
The plasma proteome has about 1,000 proteins, not 20,000. What's more, almost all the protein by weight is in the most abundant twenty proteins. All other proteins are present in only trace amounts - roughly a billion times less abundant than the common ones. Also, some proteins appear in several splice forms.
Cellular proteomes have more proteins than plasma, but share these features:
- Not every protein is in each proteome.
- Many proteins in the proteome have several forms.
- A small number of proteins make up the bulk of the proteome.
