From simplicity to complexity: The size of the genomes of human pathogens

Abstract

Harold J. Morowitz; Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia. (e-mail: morowitz@gmu.edu) A substantial number of bacterial species have now been sequenced and show a surprising range of genome sizes. If we examine a recent table of human pathogens, the reported sizes range from 582,970 base pairs for the smallest genome of Mycoplasma genitalium to 7,010,000 base pairs for the versatile versaphile, Burkholderia multivorans. The ratio is about 12. To date, no pathogens appear above Burkholderia. The smallest, Mycoplasma genitalium, has been chosen by the Venter Institute to synthesize a cell. The largest of the listed taxa are distributed over the entire size range. The lower size range consists of obligate heterotrophs, difficult to culture and infecting various human organs. They may be genitally or orally transmitted or exchanged by other direct human-to-human contact. Phylogeny is usually determined by 16S RNA. Going outside of human pathogens, the largest genome reported is 13,033,779 base pairs for the Proteobacterium, Sorangium cellulosum or 22.4 times as large as the smallest genome. Sometime before the beginning of the Cambrian period, bacteria began to find niches within and upon the surface of the animalia. These evolved, along with the evolution of the host and changes in the bacterial genome leading to a large number of bacterial taxa that are animal pathogens or commensals. Today, we examine a group of 78 bacteria that are common human pathogens. For purposes of comparison, we note that fully functional autotrophs which are probably ancestral to all bacteria seem to require between 1.5 and 2 megabase pairs. If we look at taxa with smaller genomes, they appear to have lost gene function in three ways. First, they derive almost all necessary structural and functional monomers from the host. Hence, they have lost the genes for autotrophic synthesis. Second, they are a group having defective cell walls or complete loss of cell walls, thus robbing the immune system of targets. They are not very stable outside the host, and thus tend to be transmitted orally and genitally. These groups include Mycoplasma, Chlamydia, Treponema, Rickettsia, and Gardnerella. They survive by being minimalists living in ecosystems, where everything is supplied and they have few molecular signals to trigger the host defenses.