THE CONTENT OF THE GENOME

KEY TERMS:

• The genome is the complete set of sequences in the genetic material of an organism. It includes the sequence of each chromosome plus any DNA in organelles.
• The transcriptome is the complete set of RNAs present in a cell, tissue, or organism. Its complexity is due mostly to mRNAs, but it also includes noncoding RNAs.
• The proteome is the complete set of proteins that is expressed by the entire genome. Because some genes code for multiple proteins, the size of the proteome is greater than the number of genes. Sometimes the term is used to describe complement of proteins expressed by a cell at any one time.

The key question about the genome is how many genes it contains. We can think about the total number of genes at four levels, corresponding to successive stages in gene expression:

• The genome is the complete set of genes of an organism. Ultimately it is defined by the complete DNA sequence, although as a practical matter it may not be possible to identify every gene unequivocally solely on the basis of sequence.
• The transcriptome is the complete set of genes expressed under particular conditions. It is defined in terms of the set of RNA molecules that is present, and can refer to a single cell type or to any more complex assembly of cells up to the complete organism. Because some genes generate multiple mRNAs, the transcriptome is likely to be larger than the number of genes defined directly in the genome. The transcriptome includes noncoding RNAs as well as mRNAs.
• The proteome is the complete set of proteins. It should correspond to the mRNAs in the transcriptome, although there can be differences of detail reflecting changes in the relative abundance or stabilities of mRNAs and proteins. It can be used to refer to the set of proteins coded by the whole genome or produced in any particular cell or tissue.
• Proteins may function independently or as part of multiprotein assemblies. If we could identify all protein-protein interactions, we could define the total number of independent assemblies of proteins.

The number of genes in the genome can be identified directly by defining open reading frames. Large scale mapping of this nature is complicated by the fact that interrupted genes may consist of many separated open reading frames. Since we do not necessarily have information about the functions of the protein products, or indeed proof that they are expressed at all, this approach is restricted to defining the potential of the genome. However, a strong presumption exists that any conserved open reading frame is likely to be expressed.

Another approach is to define the number of genes directly in terms of the transcriptome (by directly identifying all the mRNAs) or proteome (by directly identifying all the proteins). This gives an assurance that we are dealing with bona fide genes that are expressed under known circumstances. It allows us to ask how many genes are expressed in a particular tissue or cell type, what variation exists in the relative levels of expression, and how many of the genes expressed in one particular cell are unique to that cell or are also expressed elsewhere.

Concerning the types of genes, we may ask whether a particular gene is essential: what happens to a null mutant? If a null mutation is lethal, or the organism has a visible defect, we may conclude that the gene is essential or at least conveys a selective advantage. But some genes can be deleted without apparent effect on the phenotype. Are these genes really dispensable, or does a selective disadvantage result from the absence of the gene, perhaps in other circumstances, or over longer periods of time?