Prehistory of Potyviruses Table 5. Estimates of the date of the major radiation of potyviruses. Virus1 PPV Australian potyviruses American CAbMVs American PRSVs Mean of viruses #2-4 1.40 1.173 1.397 1.25 1.273 0.6354 0.7452 0.778 0.747 0.7567 4532 6353 5565 5976 5965 100 75 500 300 - 453 847 111 198 - Rate of evolution (61024 ns/s/yr) Length of branch from Estimate2 of radiation radiation (ns/s) date (YBP) Calibration node date3 (YBP) Accuracy4: radiation years per node decade. 1See text for name abbreviations and descriptions of viruses. 2See text for details of estimates. 3The date (YBP) of the node used to calibrate each evolutionary rate estimate. 4The number of years that the estimated date of the major radiation would change for every decade that the assumed date of the node is changed. doi:10.1371/journal.pone.0002523.t005 over-exploit the resources that had supported them in the Pleistocene. In seeking new resources to support themselves, humans progressively selected and domesticated species that provided food and other materials. Successive rounds of selection and dependence provided the ‘selective ratchet’ leading to domestication of suitable species, but this was only possible because the predictable climate allowed the lengthy selective process of adaptation and domestication to proceed. Thus agriculture appeared more or less contemporaneously, but independently, in nine regions of the world linked only by the climatic predictability and stability of the Holocene. The ‘emergence’ and spread of viruses also depends crucially on climate [70,71]. We therefore suggest that the stable Holocene climate also fostered viruses with particular ecological life styles that preadapted them to a world increasingly dominated by agriculture. Potyviruses are spread by migrating aphids. More than 200 species of aphids spread potyviruses [2,72], and most are from the subfamily Aphidinae (Myzus, Macrosiphum and Myzus species) [73]; each potyvirus may be spread by many different aphid species and each aphid species may transmit many potyviruses. Aphids originated in the late Cretaceous about 100 million years ago, but the Aphidinae which comprises about half of the 4700 described species and genera of aphids alive today come from their most recent radiation which occurred in the late Tertiary less than ten million years ago [74,75]. The aphidines are unusual among phytophagous insects in that many alternate between woody winter hosts, and herbaceous summer host species on which they reproduce parthenogenetically [75]. Aphids locate their preferred hosts by flying from plant to plant, briefly probing all the plants on which they alight along the way until they find those hosts. This behaviour is one of the factors that enables them to be efficient vectors of viruses, such as potyviruses. Thus it is likely that agricultural crops provide aphidines with a predictable succession of suitable summer herbaceous hosts on which they can reproduce rapidly and produce very large migrant populations. Potyviruses have been shown experimentally to adapt to novel host species when serially passaged in them [76,77], and thus large populations of aphids, repeatedly passaging potyviruses as they migrate through genetically uniform crops, probably provide the conditions that specifically drive potyvirus speciation. Since the mid-Holocene, agriculture has spread around the world, on foot at first, enabling aphids and potyviruses to spread, speciate and attain their current dominance. The major radiation revealed by the phylogeny of extant potyviruses may not necessarily have coincided with the event that produced the first potyvirus, for while the progenitor potyvirus was constrained as a single population, recombination and successive selective ‘sweeps’ within that population would have ensured that its origin could not be revealed by phylogenetic analysis. However when, as a result of host specialization and geographical separation, discrete lineages were able to persist as separate diverging populations, then evidence of the divergence could be detected by comparing gene sequences from the separate populations. Diamond [41] has linked the emergence and spread of human ‘crowd diseases’, such as ‘flu, measles and smallpox, with the rise of agriculture. He suggested that increases in the populations of human beings and the animals they domesticated, and the close interaction between those populations, led to the emergence of zoonotic diseases and their eventual specialization and restriction to the human population. In this paper we have reported our conclusion that, for basically the same reasons, agriculture also stimulated the emergence of the potyviruses.and their dominance in crops. Supporting Information List S1 Found at: doi:10.1371/journal.pone.0002523.s001 (0.03 MB DOC) List S2 Found at: doi:10.1371/journal.pone.0002523.s002 (0.03 MB DOC) List S3 Found at: doi:10.1371/journal.pone.0002523.s003 (0.03 MB DOC) List S4 Found at: doi:10.1371/journal.pone.0002523.s004 (0.02 MB DOC) List S5 Found at: doi:10.1371/journal.pone.0002523.s005 (0.03 MB DOC) List S6 Found at: doi:10.1371/journal.pone.0002523.s006 (0.02 MB DOC) List S7 Found at: doi:10.1371/journal.pone.0002523.s007 (0.03 MB DOC) Acknowledgments We thank Dr Vic Eastop for information about aphids, and with Dr Lute Bos and Professor Bryan Harrison for reading an early draft of this paper. We thank Dr Denis Fargette and the other unnamed referee for their very helpful comments. Author Contributions Conceived and designed the experiments: MG AG KO. Analyzed the data: MG AG MP KO. Wrote the paper: MG AG MP KO. PLoS ONE | www.plosone.org 9 June 2008 | Volume 3 | Issue 6 | e2523