The Age of Bacteria
(September 22nd, 2016) How long have humans and animals been plagued by pathogenic bacteria? In some cases, bacterial-human evolution is closely coupled.
Everybody knows the feeling of an upcoming cold, stomach infection or serious flu. We are surrounded by pathogenic bacteria and regard it as normal that they can infect us. But if we look back at human evolution, might there once have been a glorious time when humans lived happily without any of these unpleasant infections? This question is difficult to address without getting into a time machine and travelling back to the dawn of mankind. However, in the absence of time machines, researchers have come up with another idea: To model the evolution of bacteria as they have historically infected humans.
In a recent article, Mark Achtman at the University of Warwick, summarises his knowledge on the ages of Yersinia pestis, Mycobacterium tuberculosis and Helicobacter pylori. And his knowledge is wide, indeed. Achtman is one of principal researchers in the population genetics of pathogenic bacteria with almost 50 years experience in this field. In his recent publication, he combined studies on extant bacteria with genomic data from ancient species. Samples of ancient DNA (aDNA) come from archaeological sites - whenever archaeologists find a well-preserved human body, or better a mummy, they isolate the pathogenic bacteria on it. In this way, they obtain bacterial aDNA as well as an estimation of its occurrence in human history.
This can be done by looking at mutations. When did a certain mutation occur? Studies on E. coli and S. enterica, which are thought to have separated 160 million years ago, gave researchers a constant molecular clock rate of 4x10-9 substitutions per nucleotide per year. Using this estimation, the age of other bacterial taxa can be calculated. But since different taxa mutate at different rates, the clock rates slow down with time. Therefore, each taxon needs its own molecular clock – only then can a genetic tree be planted. Achtman now combined these trees with historical data, such as outbreaks of the plague in Alpine villages.
One of his favourite pathogens is Mycobacterium tuberculosis, the causative agent of tuberculosis. However, the hunt for ancient DNA turned out to be very difficult. Achtman found only two studies in which ancient M. tuberculosis DNA had been sequenced. The older one is from Peruvian Indians who died about 1,000 years ago. The more recent one is from a crypt in Hungary, containing bodies from the eighteenth and early-nineteenth century. Both studies revealed a similar clock rate for M. tuberculosis, which leads Achtman to estimate that the bacterium has been infecting humans for at least 5,000 years.
Mark Achtman, together with various colleagues from Germany, Ireland and the UK, also looked at one of the most infamous disease-causing bacteria: Yersinia pestis. Y. pestis can cause three types of infections, i.e. pneumonic, septicemic, and bubonic plagues. Luckily, medical and historical records on plagues are fairly good. After digging through all these records and genetic trees, Achtman concludes that Y. pestis was responsible for the last three pandemics in Europe and Asia. “Y. pestis has swept across Asia on multiple occasions over the last 5,000 years or longer”, he writes.
For 20 years or so, Achtman has also been intrigued by the large genetic diversity of Helicobacter pylori. H. pylori finds its only natural host in humans and causes chronic gastritis all over the planet. So the population geneticist and his co-workers collected samples from different human populations at different locations – ending up with over 2,000 different H. pylori strains. They genotyped these bacterial strains and found astonishingly similar patterns in genetic diversity to the human hosts. Thus, Achtman believes that humans already carried H. pylori when they migrated out of Africa, some 60,000 years ago. The bacterium then diverged parallel to the humans.
Having now shed some light on the evolutionary biology of gastritis, tuberculosis and plague, Achtman sees his work preparing the way towards a better future. He believes that “we will soon gain even more biological insights into these diseases, and hopefully also into other invasive diseases, especially if biologists and historians collaborate even more strongly.”
Picure: Steven Lokwan/Biology Reports, 2006