Genome reduction (Genome degradation) is the process by which a genome shrinks relative to its ancestor. Genomes fluctuate in size regularly, especially in Bacteria, but in some situations a genome has drastically lost content in some period.

The most evolutionary significant cases of genome reduction may be the eukaryotic organelles that are derived from bacteria. The mitochondrion and plastid. These organelles are descended from endosymbionts, which could only survive within the host cell and which the host cell likewise needs for survival. Many mitochondria have less than 20 genes in their entire genome, whereas a free-living bacteria generally has at least 1000 genes. Many genes have been transfered to the host nucleus, while others have simply been lost and their function replaced by host processes.

Other bacteria have become endosymbionts or obligate intracellular pathogens and experienced extensive genome reduction as a result. This process seems to be dominated by genetic drift resulting from small population size, low recombination rates, and high mutation rates, as opposed to selection for smaller genomes.

A cyanobacterium also shows signs of genome reduction, but with continued selection.