Yersinia pestis: microevolution and origin Alexandre Yersin is credited with isolating the causative agent for plague (his namesake, Yersinia pestis) in 1894 (Perry and Fetherston 1997). As the announcement of the discovery was being made, the third pandemic of plague, this time originating in China and spreading along shipping routes that intersected Hong Kong, was underway (Achtman et al. 1999). The death toll from plague, at least during recorded history, has been estimated at approx. 200 million (Perry and Fetherston 1997). A large proportion of these fatalities occurred during the three pandemics that swept through different portions of the known world: (i) the Justinian plague from 541 to 544 ad in the Mediterranean basin, Mediterranean Europe, and the Middle East;

(ii) the European Black Death from 1347 to 1351 ad (followed by epidemic cycles until the nineteenth century); and (iii) the pandemic begun in the Yunnan province of China around 1855 that subsequently spread via steamship routes to Africa, Australia, Europe, Hawaii, India, Japan, the Middle East, the Philippines, North America, and South America (Perry and Fetherston 1997). Significantly, Y. pestis is now well defined as a derivative of the rarely lethal, enteric bacterial species Yersinia pseudotuberculosis (Achtman et al. 1999, 2004; Parkhill et al. 2001; Chain et al. 2004). In the context of this book, the question we need to ask is, did genetic transfer play a role in the evolution of this pathogen? More specifically, did genetic transfer result in the origin of adaptations necessary for the ecological shift from a gastrointestinal bacterial species, transferred through contaminated food and water, into a 'systemic invasive infectious' disease-causing pathogen (Parkhill et al. 2001) transferred either sub-cutaneously by an insect intermediate or through the air by infected humans? These questions are now answerable using data from studies of both the population genetic structure and genomic constitution of Y. pestis and its congeners (Achtman et al. 1999, 2004; Parkhill et al. 2001; Chain et al. 2004).

Achtman and his colleagues carried out two genetic surveys (Achtman et al. 1999, 2004) to define microevolutionary patterns within Y. pestis. In the first of these they estimated the population genetic structure of three Yersinia species (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica) by collecting (i) partial sequence data from six genes (dmsA, glnA, manB, thrA, tmk, trpE) and (ii) RFLP data using the insertion element IS100 as a probe. The gene sequence information was collected for worldwide samples of Y. pestis (36 strains), Y. pseudotuberculosis (12 strains), and Y. enterocolitica (13 strains). The RFLP data were collected from 49 strains, representing three biotypes (i.e. biovars) of Y. pestis. Though no differences were detected in their virulence or pathology in humans or other animal hosts, these biovars had been defined previously by their ability to convert nitrate to nitrite and to ferment glycerol (Perry and Fetherston 1997). The RFLP data allowed an assessment of microevolu-tionary patterns, independent of phenotype, within Y. pestis (Achtman et al. 1999). The conclusions from this first analysis were summarized by the title of the paper containing these data, 'Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis' (Achtman et al. 1999). It was thus found that the plague bacteria differed little in sequence variation from either of its congeners and, in particular, was highly similar to Y. pseudotuberculosis. This study did however detect molecular variation that clustered the three biovars into separate clades.

The second analysis of Y. pestis population genetic structure also defined microevolution-ary/population genetic structure within and among the strains sampled (Achtman et al. 2004). However, this analysis did not find reciprocal monophyly for the various biovars. Instead geographic origin of the samples was a better predictor of phylogenetic patterning. This study did define the time of origin for the Y. pestis lineage as being c.10 000-13 000 years before present (YBP), with a cladogenetic event occurring some 6500 YBP giving rise to strains more commonly associated with human populations (Achtman et al. 2004).

Yersinia pestis: lateral transfer, gene loss, and the evolution of virulence

Two analyses, both using a genomic approach, illustrate the diverse array of genetic processes that have contributed to the evolution of Y. pestis. Conclusions from the first of these, a study by Parkhill et al. (2001), emphasized the role of genetic exchange in giving rise to the evolutionary trajectory resulting in plague. First, these authors detected sequence footprints (i.e. insertion sequence element perfect repeats and anomalous GC base-composition biases) in the genome of Y. pestis indicating numerous recombination events (Parkhill et al. 2001). Second, they discovered evidence for widespread gene inactivation in the Y. pestis genome, relative to its sister taxon Y. pseudotuberculosis. The large-scale gene inactivation was indicated by the presence of approx. 150 pseudogenes. Specifically, they detected numerous genes thought to be associated with the ancestral, enteric-bacterial habitat that had been preferentially silenced (Parkhill et al. 2001). Third, these authors argued that Y. pestis acted as the recipient of DNA from multiple donors, including bacteria and viruses (Parkhill et al. 2001). The data assembled in this analysis suggested that Y. pestis had developed adaptations as a result of both lateral exchange and gene silencing.

In contrast to Parkhill et al. (2001), the conclusions drawn from a more recent study (Chain et al. 2004) emphasized the role of gene loss and modification in the evolutionary pathway leading to the plague bacterium. These latter authors thus concluded that 'Extensive insertion sequence-mediated genome rearrangements and reductive evolution through massive gene loss . . . appear to be more important than acquisition of genes in the evolution of Y. pestis' (Chain et al. 2004). Yet, even with this emphasis, these authors detected a role for lateral transfer in producing 32 Y. pestis-specific chromosomal genes as well as two Y. pestis-specific plasmids. Significantly, one of these unique plasmids carries a gene that encodes phospholipase D (Hinnebusch et al. 2002; Hinchliffe et al. 2003). This gene product has been shown to be necessary for the viability of the plague bacteria in the midgut of its vector, the rat flea Xenopsylla cheopsis (Hinnebusch et al. 2002). Its function is believed to involve protection of the bacterium from digestion by a blood plasma cytotoxic digestion product found in the gut of X. cheopsis. Put into context, the plague bacterium has, since the divergence of the Y. pestis and Y. pseudotuberculosis lineages c.10 000-13 000 YBP,

(i) acquired 32 chromosomal genes and two plas-mids containing genes of key function for the bacterium's life history and (ii) lost, through deletion or silencing, approx. 470 genes present in Y. pseudotuberculosis (Parkhill et al. 2001; Chain et al. 2004).

Taken together, the results of the various studies involving Y. pestis may be best reflected by the following quote: 'The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve' (Parkhill et al. 2001). A multitude of genetic events, including extensive genetic exchange, followed by natural selection, have molded the evolutionary trajectory of this organism.

This same conclusion has also been drawn from over three decades of studies involving a very different species group, the Darwin's finches (genus Geospiza). Obviously, like the Louisiana irises, the genetic exchange among species of Geospiza results from sexual reproduction and introgres-sion, rather than lateral gene transfer. Yet, like the plague bacterium and Louisiana irises, studies into this group of organisms did not begin with an assumption of genetic exchange-derived evolution. Instead, the realization that a web-of-life metaphor described better the pattern of evolutionary diversification in this model system developed as data were collected from observations of natural populations and through experiments. As such, the evolutionary analyses into Darwin's finch species reflect another excellent example of how studies of genetic exchange have evolved as more and more data came to light.

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