Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor.

Rhinoviruses are the most common causes of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino acid substitutions at exposed sites in the capsid proteins VP2, VP3, and VP1 tend to be elevated in minor-group relative to major-group viruses, while rates at buried sites show no consistent differences. A reanalysis of historical virus watch data also indicates a higher immunogenicity of minor-group viruses, consistent with our findings about evolutionary rates at amino acid positions most directly exposed to immune surveillance. The increased immunogenicity and speed of evolution in minor-group lineages may contribute to the very large numbers of rhinovirus serotypes that coexist while differing in virulence.IMPORTANCE Most colds are caused by rhinoviruses (RVs). Those caused by a subset known as the minor-group members of rhinovirus species A (RV-A) are correlated with the inception and aggravation of asthma in at-risk populations. Genetically, minor-group viruses are similar to major-group RV-A, from which they were derived, although they tend to elicit stronger immune responses. Differences in their rates and patterns of molecular evolution should be highly relevant to their epidemiology. All RV-A strains show high rates of amino acid substitutions in the capsid proteins at exposed sites not previously identified as being immunogenic, and this increase is significantly greater in minor-group viruses. These findings will inform future studies of the recently discovered RV-C, which also appears to exacerbate asthma in adults and children. In addition, these findings draw attention to the difficult problem of explaining the long-term coexistence of many serotypes of major- and minor-group RVs.

A new species of big-eared climbing rat, genus Ototylomys (Cricetidae: Tylomyinae), from Chiapas, Mexico.

An allopatric population of big-eared climbing rats (Ototylomys) from the Northern Highlands of Chiapas, Mexico, is described as a new species. The new taxon is part of a unique montane rainforest community that includes several other endemic species in the limited geographic range between the Río Grijalva and the Central Depression of Chiapas. Several cranial, external, and molecular characters distinguish this new species of big-eared climbing rat from its more widely distributed congener, Ototylomys phyllotis. We performed principal component and discriminate function analyses of cranial measurements, and found that specimens of the new species consistently could be distinguished from other Ototylomys with strong statistical support. Compared with exemplars of Ototylomys from elsewhere in their range, the new species possesses a karyotype that differs by 3 additional biarmed chromosome pairs, is fixed or nearly fixed for distinct electromorphs at 12 allozyme loci, and the mean genetic distance exceeds 14%, based on comparisons of the mitochondrial cytochrome b gene between the new species of Ototylomys and representatives of O. phyllotis. The restricted distribution in montane karst rainforest suggests that the species and its habitat may be a matter of conservation concern.

Una población alopátrica de rata orejuda trepadora (Ototylomys) de las Tierras Altas del Norte de Chiapas, México se describe como una nueva especie. El nuevo taxón es parte de una comunidad única de bosque lluvioso montano que incluye varias especies endémicas en el área de distribución geográfica limitada entre el Río Grijalva y la Depresión Central de Chiapas. Varios caracteres craneales, externos, y moleculares distinguen la nueva rata orejuda trepadora de su congénere más ampliamente distribuido, Ototylomys phyllotis. Se realizaron análisis de componentes principales y de función discriminante de los caracteres craneales, y se encontró que los especímenes de La Pera fueron consistentemente distinguidos de otros Ototylomys con un fuerte soporte estadístico. En comparación con ejemplares de Ototylomys del rango, la nueva especie posee un cariotipo que difiere por 3 pares adicionales de cromosomas biarmados, está fijo o casi fijo por distintos electromorfos en 12 loci alozímicos. Adicionalmente, la media de la distancia genética comparada del gen mitochondrial citocromo b entre la nueva especie de Ototylomys y representantes de O. phyllotis, excede el 14%. La distribución restringida en el bosque lluvioso montano kárstico sugiere que la especie y su hábitat pueden ser de importancia para la conservación.

Evolution of Picornaviridae: an examination of phylogenetic relationships and cophylogeny.

Picornaviruses are responsible for some of the most common and debilitating illnesses affecting humans and animals worldwide. To extend our knowledge of the evolution of picornaviruses and their molecular epidemiology, phylogenetic relationships among 11 genera and the unassigned seal picornavirus type 1 were estimated from the conserved proteins 2C, 3C(pro), and 3D(pol). Each gene was analyzed separately and as a combined dataset. Different tree topologies were recovered from each gene. However, their sequences were determined to be combinable based on our finding of no recombination among genera and failing to reject the hypothesis of homogeneity among datasets using ILD tests. The combined data tree topology was identical to the 3D(pol) gene tree; a topology largely consistent with previous phylogenetic hypotheses based on 3D(pol) and the coding genome. Phylogenetic trees estimated from six phenotypic characters were not congruent with those recovered from molecular datasets; further supporting the hypothesis that viral phenotypes are highly plastic. Finally, we tested the hypothesis of host-virus cophylogeny. Both global and individual tests of the relationships between host and virus trees failed to detect a significant association. These results emphasize the importance of horizontal transmission among host species for picornavirus diversification rather than vertical transmission accompanying speciation.

Phylogenetic relationships and molecular adaptation dynamics of human rhinoviruses.

Human rhinoviruses (HRVs) are responsible for nearly 50% of all common cold infections. Ordinarily, HRV infections are mild and self-limiting; nonetheless, every year they result in significant loss of economic productivity and substantial inappropriate antibiotic use. Development of effective vaccine and antiviral prophylaxis against HRV has been hampered by the extensive antigenic diversity present among the nearly 100 serotypes. To gain new insights into the evolutionary processes that create the genetic diversity present among HRVs, we tested for recombination and selection for individual genes and the coding genome for 45 HRV serotypes using estimated phylogenetic relationships. Although the structural capsid genes and nonstructural genes recovered incongruent tree topologies, no recombination was detected using substitution methods. Therefore, the coding genome was determined to be appropriate for phylogenetic tests. Results of the Shimodaira-Hasegawa (SH) test support the hypothesis that the capsid genes recover a different evolutionary history than the nonstructural genes. Our best phylogenetic estimate based on the coding genome suggests that HRV-B is more closely related to enterovirus than to HRV-A; however, several alternative phylogenetic hypotheses were not rejected by the SH test. Positive selection was examined by using two different approaches; d(N)/d(S) rate ratio and the physicochemical phenotypes for 31 amino acid properties. Analyses using d(N)/d(S) failed to detect positive selection. However, protein phenotypic expression appears to be a more sensitive approach. There was extensive stabilizing and destabilizing positive selection in HRV-A major and HRV-B serotypes for all proteins, except in 3A in HRV-B, which overlapped with functional, structural, and to a greater extent in uncharacterized genomic regions. In contrast, the evolution of HRV-A minor serotypes appears to be driven primarily by destabilizing selection. Our results demonstrate that HRV-A major, HRV-A minor, and HRV-B serotypes have not been similarly influenced by purifying selection.

The evolution of foot-and-mouth disease virus: impacts of recombination and selection.

Foot-and-mouth disease virus is an economically important animal virus that exhibits extensive genetic and antigenic heterogeneity. To examine the evolutionary forces that have influenced the population dynamics of foot-and-mouth disease virus, individual genes and the coding genomes for the Eurasian (Asia1, A, C, and O) serotypes were examined for phylogenetic relationships, recombination, genetic diversity and selection. Our analyses demonstrate that paraphyletic relationships among serotypes are not as prevalent as previously proposed and suggest that convergent evolution might be obscuring phylogenetic relationships. We provide evidence that identification of recombinant sequences and recombination breakpoint patterns among and within serotypes are heavily dependent on the level of genetic diversity and convergent characters present in a particular data set as well as the methods used to detect recombination. Here, we also investigate the impact of adaptive positive selection on the capsid proteins and the non-structural genes 2B, 2C, 3A, and 3Cpro to identify genome regions involved in genetic diversity and antigenic variation. Two different categories of positive selection at the amino acid level were examined; conservative (stabilizing) selection that maintains particular phenotypic properties of an amino acid residue and radical (destabilizing), and selection that dramatically alters the phenotype and potentially the functional and/or structural features of the protein. Approximately, 29% of residues in the capsid proteins were under positive selection. Of those, 64% were under the influence of destabilizing selection, 80% were under the influence of stabilizing selection, and 44% had phenotypic properties influenced by both selection types. The majority of residues under selection (74%) were located outside of known antigenic sites; suggestive of additional uncharacterized epitopes and genomic regions involved in antigenic drift.