Serial evolutionary networks of within-patient HIV-1 sequences reveal patterns of evolution of X4 strains

Background The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation of the mutational pathways of a viral population in a within-host environment. The longitudinal representation of the evolutionary networks was complemented with charts of clinical markers to facilitate correlation analysis between pertinent clinical information and the evolutionary relationships. Results Analysis based on the predicted networks suggests the following:: significantly stronger recombination signals (p = 0.003) for the inferred ancestors of the X4 strains, recombination events between different lineages and recombination events between putative reservoir virus and those from a later population, an early star-like topology observed for four of the patients who died of AIDS. A significantly higher number of recombinants were predicted at sampling points that corresponded to peaks in the viral load levels (p = 0.0042). Conclusion Our results indicate that serial evolutionary networks of HIV sequences enable systematic statistical analysis of the implicit relations embedded in the topology of the structure and can greatly facilitate identification of patterns of evolution that can lead to specific hypotheses and new insights. The conclusions of applying our method to empirical HIV data support the conventional wisdom of the new generation HIV treatments, that in order to keep the virus in check, viral loads need to be suppressed to almost undetectable levels.

Atlantic Ais in the Sixteenth and Seventeenth Centuries: Maritime Adaptation, Indigenous Wrecking, and Buccaneer Raids on Florida’s Central East Coast

The Ais were a Native American group who lived along the Atlantic shoreline of Florida south of Cape Canaveral. This coastal population’s position adjacent to a major shipping route afforded them numerous encounters with the Atlantic world that linked Europe, Africa, the Caribbean, and the Americas. Through their exploitation of the goods and peoples from the European shipwrecks thrown ashore, coupled with their careful manipulation of other Atlantic contacts, the Ais polity established an influential domain in central east Florida during the sixteenth and seventeenth centuries. The pre-contact peoples of Florida’s east coast, including the ancestors of the Ais, practiced a maritime adaptation concentrated on the exploitation of their bountiful riverine, estuarine, and marine environments. The Ais then modified their maritime skills to cope with the opportunities and challenges that accompanied European contact. Using their existing aquatic abilities, they ably salvaged goods and castaways from the Spanish, French, English, and Dutch vessels dashed on the rocks and reefs of Florida’s coast. The Ais’ strategic redistribution of these materials and peoples to other Florida Native Americans, the Spaniards of St. Augustine, and other passing Europeans gained them greater influence. This process, which I call indigenous wrecking, enabled the Ais to expand their domain on the peninsula. Coastal Florida Native Americans’ maritime abilities also attracted the attention of Europeans. In the late seventeenth century, English buccaneers and salvagers raided Florida’s east coast to capture indigenous divers, whom they sent to work the wreck of a sunken Spanish treasure ship located in the Bahamas. The English subsequently sold the surviving Native American captives to other Caribbean slave markets. Despite population losses to such raids, the Ais and other peoples of the east coast thrived on Atlantic exchange and used their existing maritime adaptation to resist colonial intrusions until the start of the eighteenth century. This dissertation thus offers a narrative about Native Americans and the Atlantic that is unlike most Southeastern Indian stories. The Ais used their maritime adaptation and the process of indigenous wrecking to engage and exploit the arriving Atlantic world. In the contact era, the Ais truly became Atlantic Ais.