Lecture 26 Jan 2001 Per Kraulis

The genomes

4. Analysing a genome

So, what does one do with a complete genome? After all, a sequenced genome consists only of so many bases in a defined order. Analysis is obviously necessary in order to obtain biologically interesting information.

The analysis of a genome covers many different aspects. Here follows a list of the most common ones, but it is clear that entirely novel ways of analysing a complete genome can be invented. The potential for interesting discoveries in the complete genomes is great; we have probably just scratched the surface so far.

• Define the location of genes (coding sequences, regulatory regions): gene prediction (identification).
  • Gene prediction ab initio using software based on rules and patterns. Find Open Reading Frames (ORFs), with additional criteria for good start sequence for a gene. This is considered reasonably easy for bacteria, but is very difficult for eukaryotes.
  • Gene identification through alignment with know proteins and EST sequences (Expressed Sequence Tags; mRNA sequences).
  • Gene prediction through similarity with proteins or ESTs in other organisms.
  • Gene prediction through comparison with other genomes; conserved regions are probably coding or regulatory regions. This is called synteny, and is very promising for analysis of higher eukaryote genomes.

• Annotation of the genes: Compare with genes/proteinsof known function in other organisms. This is essentially the same as labelling the gene.

• Functional classification. Broad groups of functional characterization, such as 'ribosomal proteins', 'nucleotide metabolism', 'signal transduction'.

• Metabolic pathways.
  • Are any common pathways missing?
  • Are there 'gaps' (missing enzymes) in some pathways?
  • Compare identified pathways with the life style of the organism.

• Evolutionary history
  • Internal genome duplications can sometimes be detected.
  • Gene decay can sometimes be characterized: genes that are on their 'way out' after duplication, or because the life style of the organism has changed.
  • Horisontal gene transfer: genes that have been acquired from another organism.