The evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected from individuals in a prospective community-based cohort, they are broadly representative of natural infections with seasonal viruses. Consistent with a neutral model of evolution, sequence data from 49 serially sampled individuals illustrated the dynamic turnover of synonymous and nonsynonymous single nucleotide variants and provided little evidence for positive selection of antigenic variants. We also identified 43 genetically-validated transmission pairs in this cohort. Maximum likelihood optimization of multiple transmission models estimated an effective transmission bottleneck of 1-2 genomes. Our data suggest that positive selection is inefficient at the level of the individual host and that stochastic processes dominate the host-level evolution of influenza viruses.
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided. All sequence reads have been deposited to NCBI's BioProject under accession number PRJNA412631.
Whole genome sequencing of Influenza isolates from a prospective household cohortPublicly available at the NCBI BioProject (accession no: PRJNA412631).
- Adam S Lauring
- Adam S Lauring
- John T McCrone
- Arnold S Monto
- Robert J Woods
- Arnold S Monto
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: This study was approved by the Institutional Review Board of the University of Michigan Medical School. Adults provided written informed consent for participation for themselves and their children; children 7-17 years provided oral assent.
- Richard A Neher, University of Basel, Switzerland
© 2018, McCrone et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The Early Cretaceous diversification of birds was a major event in the history of terrestrial ecosystems, occurring during the earliest phase of the Cretaceous Terrestrial Revolution, long before the origin of the bird crown-group. Frugivorous birds play an important role in seed dispersal today. However, evidence of fruit consumption in early birds from outside the crown-group has been lacking. Jeholornis is one of the earliest-diverging birds, only slightly more crownward than Archaeopteryx, but its cranial anatomy has been poorly understood, limiting trophic information which may be gleaned from the skull. Originally hypothesised to be granivorous based on seeds preserved as gut contents, this interpretation has become controversial. We conducted high-resolution synchrotron tomography on an exquisitely preserved new skull of Jeholornis, revealing remarkable cranial plesiomorphies combined with a specialised rostrum. We use this to provide a near-complete cranial reconstruction of Jeholornis, and exclude the possibility that Jeholornis was granivorous, based on morphometric analyses of the mandible (3D) and cranium (2D), and comparisons with the 3D alimentary contents of extant birds. We show that Jeholornis provides the earliest evidence for fruit consumption in birds, and indicates that birds may have been recruited for seed dispersal during the earliest stages of the avian radiation. As mobile seed dispersers, early frugivorous birds could have expanded the scope for biotic dispersal in plants, and might therefore explain, at least in part, the subsequent evolutionary expansion of fruits, indicating a potential role of bird–plant interactions in the Cretaceous Terrestrial Revolution.
Assembly pathways of protein complexes should be precise and efficient to minimise misfolding and unwanted interactions with other proteins in the cell. One way to achieve this efficiency is by seeding assembly pathways during translation via the cotranslational assembly of subunits. While recent evidence suggests that such cotranslational assembly is widespread, little is known about the properties of protein complexes associated with the phenomenon. Here, using a combination of proteome-specific protein complex structures and publicly available ribosome profiling data, we show that cotranslational assembly is particularly common between subunits that form large intermolecular interfaces. To test whether large interfaces have evolved to promote cotranslational assembly, as opposed to cotranslational assembly being a non-adaptive consequence of large interfaces, we compared the sizes of first and last translated interfaces of heteromeric subunits in bacterial, yeast, and human complexes. When considering all together, we observe the N-terminal interface to be larger than the C-terminal interface 54% of the time, increasing to 64% when we exclude subunits with only small interfaces, which are unlikely to cotranslationally assemble. This strongly suggests that large interfaces have evolved as a means to maximise the chance of successful cotranslational subunit binding.