Evolutionary studies of viral pathogens have, with few exceptions, tended to focus on individual species. If an attempt is made to place their evolution “in context,” this usually only relates to the different host species that a virus infects. For example, there is currently great interest in determining the viral and host determinants for the sustained transmission of H5N1 influenza A virus in birds as opposed to humans. Although such studies are an essential part of modern molecular epidemiology, an exploration of how the multiplicity of pathogens that co-circulate within a single host population might influence each other's evolution and etiology is strikingly absent. Similarly important questions include: What role does cross-protective immunity play in shaping microbial diversity? How widespread is ecological interference among pathogens?
Existing data already hint at the importance of evolutionary interactions among pathogens. For example, the HIV pandemic has resulted in an abundance of people with pronounced immune deficiency, stimulating a resurgence in opportunistic pathogens like Mycobacterium tuberculosis
. It is also possible that widespread immunodeficiency will assist the emergence of new pathogens [3
], perhaps by extending the infectious period of normally acute viral infections. Similarly, the nature of the interactions among the four serotypes of dengue virus has been a subject of much debate, particularly whether immunological responses to different serotypes are usually cross-protective [4
] or enhancing [5
]. Not only might these interactions dictate underlying patterns of genome evolution [6
], but they will evidently have a major bearing on successful vaccination.
Finally, it has long been known that influenza-associated mortality is largely due to secondary pneumonia caused by Streptococcus pneumoniae
]. However, although we now have a wealth of data on the genetic diversity of influenza virus in both time and space, there has been no attempt to tie these evolutionary patterns with those of the co-infecting bacterial population. Influenza virus is also just one of the respiratory pathogens that circulate in human populations, with other notables including parainfluenza virus, respiratory syncytial virus, and the abundant rhinoviruses. Despite the disease burden due to these viruses, little is known about how they interact at the evolutionary and epidemiological scales. The comparative analysis of their genome sequences, in which changes in genetic diversity (or phylogenetic structure) in one virus are placed in the context of the contemporaneous evolutionary patterns and processes exhibited by co-circulating pathogens, may provide a valuable way to study their interactions.