I've written before about ancient diseases of the ice age, but this time I'm going even further back in time, to diseases that were present in the first human-like hominids. Although many human infections only developed after human settlements and animal domistication, early human ancestors would still have been fighting off bacteria and other nasty diseases. Some of these diseases are still around today.

So how do you start exploring the age of bacteria, and trying to discover when they developed as a human-infecting species? One way to look for the age and relatedness of strains is by looking at the bacterial DNA and examining the rate of mutations that cause very small differences between bacterial strains (single nucleotide polymorphism - shown in the image below). It is also possible to identify "pseudogenes" within the bacteria - little bits of viral DNA or bacterial genes that became redundant due to a change in the bacterial lifestyle (for example genes for extracellular lifestyle that started decaying and mutating once the bacteria became fully intracellular). These can be dated using the 'molecular clock' - which assumes a steady rate of background mutation and can provide approximations of the age of genes.

The disease leprosy, caused by Mycobacteria leprae, has recently undergone this analysis and raised some interesting questions about its origins and spread. Although first recorded in humans around 600BC in India, the molecular evidence point to it being far older, possibly originating in Africa during the Paleolithic period. The lack of genetic variation between leprosy strains also points to a genetic bottleneck in the past. This is likely to have been caused by the bacteria's low rate of infection. Despite the huge amount of social stigma associated with it leprosy is not highly infectious and could easily have been almost completely lost among early human societies.

Another bacteria to have gone through the genetic analysis is Bordetella pertussis, the bacteria responsible for whooping cough. Originally thought to have passed to humans via a similar species found in domestic animals, the molecular evidence once again suggests that it has been around since before animals were first domesticated. Instead it may have evolved from the bacteria B. bronchiseptica which was present around 2.5 million years ago with a preference for infecting hominids. This makes a rather neat little story of a bacteria adapting to fit the changing hominids as they became human and evolving specifically to fit the human niche (image below by Nathan Reading)

Although this research produces some exciting outcomes, it shouldn't be taken as the last word on bacterial origins as it does sometimes come up with some questionable results. Trying to combine SNP analysis results with the molecular clock dating of pseudogenes creates some interesting paradoxes, such as pseudogenes within M. leprae that arose over 9 million years ago [EDIT This was originally incorrectly written as 'billion'], when modern humans have only existed since approximately 250,000 years ago! What is clear however is that not all diseases can be blamed on cities and animal domestication, and that some bacteria were infecting humans back when Homo sapiens was still an exciting new species to be. Deeper genome sequencing analysis and further work on dating the pseudogenes could give a fascinating look into the development of human diseases from the times of our earliest ancestors.

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Ref 1: Trueba G, & Dunthorn M (2012). Many neglected tropical diseases may have originated in the Paleolithic or before: new insights from genetics. PLoS neglected tropical diseases, 6 (3) PMID: 22479653

Ref 2: Monot, M., Honoré, N., Garnier, T., Zidane, N., Sherafi, D., Paniz-Mondolfi, A., Matsuoka, M., Taylor, G., Donoghue, H., Bouwman, A., Mays, S., Watson, C., Lockwood, D., Khamispour, A., Dowlati, Y., Jianping, S., Rea, T., Vera-Cabrera, L., Stefani, M., Banu, S., Macdonald, M., Sapkota, B., Spencer, J., Thomas, J., Harshman, K., Singh, P., Busso, P., Gattiker, A., Rougemont, J., Brennan, P., & Cole, S. (2009). Comparative genomic and phylogeographic analysis of Mycobacterium leprae Nature Genetics, 41 (12), 1282-1289 DOI: 10.1038/ng.477

Ref 3: Diavatopoulos DA, Cummings CA, Schouls LM, Brinig MM, Relman DA, & Mooi FR (2005). Bordetella pertussis, the causative agent of whooping cough, evolved from a distinct, human-associated lineage of B. bronchiseptica. PLoS pathogens, 1 (4) PMID: 16389302