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In a subdivided population, the interaction between natural selection and stochastic change in allele frequency is affected by the occurrence of local extinction and subsequent recolonization. The relative importance of selection can be diminished by this additional source of stochastic change in allele frequency. Results are presented for subdivided populations with extinction and recolonization where there is more than one founding allele after extinction, where these may tend to come from the same source deme, where the number of founding alleles is variable or the founders make unequal contributions, and where there is dominance for fitness or local frequency dependence. The behavior of a selected allele in a subdivided population is in all these situations approximately the same as that of an allele with different selection parameters in an unstructured population with a different size. The magnitude of the quantity [N.sub.e][s.sub.e], which determines fixation probability in the case of genic selection, is always decreased by extinction and recolonization, so that deleterious alleles are more likely to fix and advantageous alleles less likely to do so. The importance of dominance or frequency dependence is also altered by extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations.

In a subdivided population, local extinction and subsequent recolonization affect the fate of alleles. Of particular interest is the interaction of this force with natural selection. The effect of selection can be weakened by this additional source of stochastic change in allele frequency. The behavior of a selected allele in such a population is shown to be equivalent to that of an allele with a different selection coefficient in an unstructured population with a different size. This equivalence allows use of established results for panmictic populations to predict such quantities as fixation probabilities and mean times to fixation. The magnitude of the quantity [N.sub.e][s.sub.e], which determines fixation probability, is decreased by extinction and recolonization. Thus deleterious alleles are more likely to fix, and advantageous alleles less likely to do so, in the presence of extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations.

The interplay between population structure and natural selection is an area of great interest. It is known that certain types of population subdivision do not alter fixation probabilities of selected alleles under genie, frequency-independent selection. In the presence of dominance for fitness or frequency-dependent selection these same types of subdivision can have large effects on fixation probabilities. For example, the barrier to fixation of a fitter allele due to underdominance is reduced by subdivision. Analytic results presented here relate a subdivided population that conforms to a finite island model to an approximately equivalent panmictic population. The size of this equivalent population is different from (larger than) the actual size of the subdivided population. Selection parameters are also different in the hypothetical equivalent population. As expected, the degree of dominance is lower in the equivalent population. The results are not limited to dominance but cover any form of polynomial frequency dependence.

The population-genetic consequences of population structure are of great interest and have been studied extensively. An area of particular interest is the interaction among population structure, natural selection, and genetic drift. At first glance, different results in this area give very different impressions of the effect of population subdivision on effective population size ([N.sub.e]), suggesting that no single value of [N.sub.e] can completely characterize a structured population. Results presented here show that a population conforming to Wright's island model of subdivision with genie selection can be related to an idealized panmictic population (a Wright-Fisher population). This equivalent panmictic population has a larger size than the actual population; i.e., [N.sub.e] is larger than the actual population size, as expected from many results for this type of population structure. The selection coefficient in the equivalent panmictic population, referred to here as the effective selection coefficient ([s.sub.e]), is smaller than the actual selection coefficient (s). This explains how the fixation probability of a selected allele can be unaffected by population subdivision despite the fact that subdivision increases [N.sub.e], for the product [N.sub.e][s.sub.e] is not altered by subdivision.

Divergence of the hyperthermophilic Archaea, Pyrococcus furiosus and Pyrococcus horikoshii, was assessed by analysis of complete genomic sequences of both species. The average nucleotide identity between the genomic sequences is 70-75% within ORFs. The P. furiosus genome (1.908 mbp) is 170 kbp larger than the P. horikoshii genome (1.738 mbp) and the latter displays significant deletions in coding regions, including the trp, his, aro, leu-ile-val, arg, pro, cys, thr, and mal operons. P. horikoshii is auxotrophic for tryptophan and histidine and is unable to utilize maltose, unlike P. furiosus. In addition, the genomes differ considerably in gene order, displaying displacements and inversions. Six allelic intein sites are common to both Pyrococcus genomes, and two intein insertions occur in each species and not the other. The bacteria-like methylated chemotaxis proteins form a functional group in P. horikoshii, but are absent in P. furiosus. Two paralogous families of ferredoxin oxidoreductases provide evidence of gene duplication preceding the divergence of the Pyrococcus species.

The rate of nucleotide substitution is generally believed to be a decreasing function of effective population size, at least for nonsynonymous substitutions. This view was originally based on consideration of slightly deleterious mutations with a fixed distribution of selection coefficients. A realistic model must include the occurrence and fixation of some advantageous mutations that compensate for the loss of fitness due to deleterious substitutions. Some such models, such as so-called 'fixed' models, also predict a population size effect on substitution rate. An alternative model, presented here, predicts the near absence of a population size effect on substitution rate. This model is based on concave log-fitness functions and a fixed distribution of mutational effects on the selectively important trait. Simulations of an instance of the model confirm the approximate insensitivity, of the substitution rate to population size. Although much experimental evidence has been claimed to support the existence of a population size effect, the body of evidence as a whole is equivocal, and much of the evidence that is supposed to demonstrate such an effect would also suggest that it is very small. Perhaps the proposed model applies well to some genes and not so well to others, and genes therefore vary with regard to the population size effect.

The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non-protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing of bacterial pathogens is used by public health agencies to link cases of food poisoning caused by the same source of contamination. The vast majority of these appear to be sporadic cases associated with small contamination episodes and do not trigger investigations. We analyzed clusters of sequenced clinical isolates of Salmonella , Escherichia coli , Campylobacter , and Listeria that differ by only a small number of mutations to provide a new understanding of the underlying contamination episodes. These analyses provide new evidence that the youngest age groups have greater susceptibility to infection from Salmonella , Escherichia coli , and Campylobacter than older age groups. This age bias is weaker for the common Salmonella serovar Enteritidis than Salmonella in general. Analysis of these clusters reveals significant regional variations in relative frequencies of Salmonella serovars across the United States. A large fraction of the contamination episodes causing sickness appear to have long duration. For example, 50% of the Salmonella cases are in clusters that persist for almost three years. For all four pathogen species, the majority of the cases were part of genetic clusters with illnesses in multiple states and likely to be caused by contaminated commercially distributed foods. The vast majority of Salmonella cases among infants < 6 months of age appear to be caused by cross-contamination from foods consumed by older age groups or by environmental bacteria rather than infant formula contaminated at production sites., Competing Interests: Conflict of interest The authors declare no conflict of interest.

Importance: For decades, researchers have studied the rapid evolution of influenza A viruses for vaccine design and as a useful model system for the study of host/parasite evolution. By performing an exhaustive analysis of hemagglutinin protein (HA) sequences from 49 lineages independently evolving in birds, swine, canines, equines, and humans over the last century, our work uncovers surprising features of HA evolution. In particular, the canine H3 stalk, unlike human H3 and H1 stalk domains, is not evolving slowly, suggesting that evolution in the stalk domain is not universally constrained across all host species. Therefore, a broader multi-host perspective on HA evolution may be useful during the evaluation and design of stalk-targeted vaccine candidates., Competing Interests: The authors declare no conflict of interest.

There is great variation in the rates of sequence evolution among proteins encoded by the same genome. The strongest correlate of evolutionary rate is expression level: highly expressed proteins tend to evolve slowly. This observation has led to the proposal that a major determinant of protein evolutionary rate involves the toxic effects of protein that misfolds due to transcriptional and translational errors (the mistranslation-induced misfolding [MIM] hypothesis). Here, I present a model that explains the correlation of evolutionary rate and expression level by selection for function. The basis of this model is that selection keeps expression levels near optima that reflect a trade-off between beneficial effects of the protein's function and some nonspecific cost of expression (e.g., the biochemical cost of synthesizing protein). Simulations confirm the predictions of the model. Like the MIM hypothesis, this model predicts several other relationships that are observed empirically. Although the model is based on selection for protein function, it is consistent with findings that a protein's rate of evolution is at most weakly correlated with its importance for fitness as measured by gene knockout experiments.