Small genome variations account for wide range of diseases, victims
Rockville, MD – Surprisingly subtle differences in gene content appear to account for the stunningly large number of diseases caused by the Chlamydiae family of bacteria in a wide range of animal hosts that the pathogens infect, a new study suggests.
The investigation by scientists at The Institute for Genomic Research (TIGR) and collaborators used new techniques to compare the newly-sequenced genome of Chlamydophila caviae (formerly classified as C. psittaci GPIC) – an obligate intracellular pathogen that causes eye infections in guinea pigs – with the complete DNA sequences of three other members of the Chlamydiae family, including two that cause serious diseases in humans.
The paper, published in the mid-April issue of Nucleic Acids Research (Vol. 31, No. 8, pp. 2134-2147), found close similarity among the DNA sequences of C. caviae and three other previously-sequenced species of Chlamydiae pathogens, which attack widely different hosts and cause human diseases ranging from infectious blindness to pneumonia and possibly heart disease.
According to the analysis, nearly 800 of the 1009 annotated genes discovered in C. caviae were also found in the genomes of the other three related chlamydial bacteria: C. trachomatis, which causes chronic genital and eye infections in humans; C. pneumoniae, which causes human pneumonia, bronchitis and pharyngitis, and may also be a factor in coronary heart disease; and C. muridarum, which infects mice.
“With four complete genome sequences now available, the Chlamydiae family has become a leading microbial system for the study of the evolution of pathogens, using techniques of comparative genomics,” says Tim Read, the TIGR scientist who is the first author of the new paper.
The research project, led by TIGR President Claire M. Fraser, was supported by the National Institute of Allergy and Infectious Diseases (NIAID). Collaborators elsewhere included scientists at the University of Maryland’s Department of Oral and Craniofacial Biological Sciences; the University of British Columbia’s Center for Disease Control; and the University of Arkansas’ Department of Microbiology and Immunology.
The Chlamydiae family includes nine known species of bacteria that infect a wide range of animal and human hosts and cause a stunning array of diseases, from the sexually-transmitted chlamydia to the major cause of infectious blindness, trachoma. Recent research has also suggested potential links of C. pneumoniae to heart ailments, Alzheimer’s disease, and various other human maladies.
A recent preliminary study by scientists in Asia also has implicated Chlamydiae as a possible co-factor in the ongoing epidemic of Severe Acute Respiratory Syndrome, known as SARS. [“Novel coronavirus and severe acute respiratory syndrome,” a commentary published online in The Lancet, April 8, 2003.] The tentative link is based on preliminary evidence suggesting that prior Chlamydiae infections appear in a number of Asians who contracted SARS.
In addition to sequencing C. caviae, TIGR scientists had previously led the projects that deciphered the genomes of C. pneumoniae and C. muridarum. TIGR and other research centers are now sequencing other chlamydial species.
“There is a great deal of interest in chlamydial species now because of their possible association with chronic diseases,” said Fraser. “Comparative genomics offers a powerful new set of tools to study whether or not there is an infectious etiology in atherosclerosis and Alzheimer’s disease, for example, and also to identify potential new avenues for diagnosis and treatment.”
TIGR staff scientist Garry Myers says that evidence for the likely horizontal transfer of genes among microbial species in the Chlamydiae family also may help scientists to better understand how genes “jump” between species. For example, genes from chlamydial species that infect birds – such as the avian Chlamydia now being sequenced at TIGR – may possibly “jump” to other Chlamydiae that mainly infect humans.
Using C. caviae as a model to scrutinize the genomes of the other three sequenced Chlamydiae, the TIGR study found 171 genes on the C. pneumoniae genome that are not present in the other three sequenced Chlamydiae genomes. Scientists speculated that the presence of such novel, “niche-specific” genes within C. pneumoniae may be part of the reason why it causes persistent and invasive infections in humans. But more comparative genomics research will be needed to pinpoint the reasons for those differences.
The Institute for Genomic Research (TIGR), which sequenced the first complete genome of a free-living organism in 1995, is a not-for-profit research institute based in Rockville, Maryland. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes.