Modeling poliovirus transmission
Child in Tajikistan receiving the oral polio vaccine. Image courtesy of UNICEF/Sodiqov/2010.
Despite the success of a global eradication effort led by the World Health Organization and partners, polio outbreaks among older children and adults in some countries and reports of declining intestinal immunity after vaccination has led to proposals to include older children in vaccination campaigns, which currently target children 4 years of age and below. To determine the contribution of older children and adults to poliovirus transmission, Isobel Blake et al. (pp. 10604–10609) performed mathematical modeling with polio surveillance data from recent outbreaks among adults and found that in Tajikistan, where a 2010 outbreak led to 518 polio cases, older children and adults minimally transmitted polio, despite developing the disease, compared with children aged 0–5 years. In comparison, during a 2010 outbreak in the Republic of Congo with 442 cases, older children and adults contributed significantly to virus transmission, likely due to socioeconomic conditions that favored disease spread. The authors failed to find evidence for the role of inadequate intestinal immunity in viral spread in either outbreak but estimated that advancing immunization in Tajikistan by 2 weeks might have forestalled 130 cases. According to the authors, countries that have been polio-free might curb outbreaks by responding early rather than expanding the age range of vaccination campaigns. — P.N.
Algorithm links evolution and game theory via population genetics
Natural selection represents an extraordinarily successful mechanism that has yielded the vast complexity of organisms on the tree of life. Erick Chastain et al. (pp. 10620–10623) attempted to determine whether this complexity can be reproduced by an algorithm within reasonable time limits. The authors report that the standard equations of population genetic dynamics are comparable with repeated rounds of a game in which the players represent recombining loci, the available strategies represent alleles in those loci, and the payoff at each generation is the expected fitness of an organism across the genotypes present in the population. Assuming sexual recombination and weak selection—the condition that phenotypes have only slight advantages over one another—the authors found that loci in the game strategize by tuning the distribution of their alleles in the population according to the rules of multiplicative weight updates, a simple but powerful algorithm. The findings demonstrate a link between game theory and evolution that arises from basic population genetic dynamics and may provide insight into the maintenance of diversity in evolution, according to the authors. — T.J.
Mitochondrial heteroplasmy in healthy humans
In human cells, mitochondrial DNA can undergo mutations to form variants. This condition, known as heteroplasmy, has been implicated in diseases but its prevalence across the mitochondrial genome in healthy populations has been unclear due to small sample sizes or inadequate sequencing methods in previous studies. Kaixiong Ye et al. (pp. 10654–10659) analyzed high-quality, next-generation sequencing data of the entire mitochondrial genome for 1,085 healthy individuals from 14 global populations through the 1000 Genomes Project. The authors used algorithms that controlled for sequencing errors and technical artifacts to ensure the accurate quantification of heteroplasmy. Ninety percent of the individuals harbored at least one heteroplasmy, but the total number of heteroplasmies was low in most individuals. Moreover, 19% of all individuals carried at least one disease-associated heteroplasmy. According to the authors, the number of possibly harmful mitochondrial DNA variants in healthy individuals may increase in some cells over time and eventually reach a critical threshold to potentially cause age-related diseases. — J.W.
Lipid’s complex role in viral infection
The ATF3 transcription factor plays a key role in regulating the formation of foam cells—macrophages that contribute to the development of plaque deposits in blood vessel walls that can lead to heart attacks and strokes. Researchers previously showed that mice lacking ATF3 are more likely to develop atherosclerosis, compared with mice with ATF3, partly due to the actions of 25 hydroxycholesterol (25HC), a lipid secreted by macrophages in response to infection. Elizabeth Gold et al. (pp. 10666–10671) report that in addition to 25HC’s functions in atherosclerosis, the lipid amplifies inflammatory signaling in macrophages to mediate the antiviral response. The authors found that 25HC modulates inflammatory signaling by recruiting components of the AP-1 transcription factor, Fos and Jun, to the promoters of certain genes responsive to Toll-like receptors. The study confirms earlier findings that 25HC helps prevent influenza entry and replication in airway epithelial cells. The authors found, however, that abolishing 25HC production protects mice against influenza by preventing inflammation-induced pathology. According to the authors, the findings may help illuminate the mechanisms of highly pathogenic influenza strains and uncover strategies to protect against influenza. — A.G.
Reconstructing the population dynamics of passenger pigeons
Passenger pigeons. Image courtesy of Erin Roche (Northern Prairie Wildlife Research Center, Jamestown, ND).
Immense flocks of passenger pigeons, Ectopistes migratorius, which went extinct a century ago, once thronged the skies over eastern North America, their numbers reaching an estimated 3–5 billion in the 1800s. Chih-Ming Hung et al. (pp. 10636–10641) sequenced ancient DNA extracted from the toe pad tissues of three museum specimens of passenger pigeons collected from across the birds’ breeding range, hoping to determine whether humans, long assumed to have contributed to the pigeons’ extinction, may have exacerbated a natural decline in the pigeons’ population, precipitating their extinction in merely five decades. The authors mapped the ancient DNA sequences against the genome of a domestic pigeon and found that, given the passenger pigeons’ census population size, estimates of the birds’ genetically effective population size—a measure tied to genetic drift and variation—were much lower than expected, hinting at dramatic natural population changes, common among species such as the Australian plague locust, which undergoes rapid, outbreak-like rise and fall in numbers. Ecological modeling of climate in the pigeons’ breeding range, fossil pollen records of oak tree distribution, and estimates of acorn production and consumption bolstered the likelihood of drastic and episodic natural population changes among passenger pigeons. According to the authors, such dynamics may have rendered the birds vulnerable to human influences and tipped them toward extinction. — P.N.
Emergence of deadly flu viruses
Highly pathogenic bird flu viruses cause economic losses to the poultry industry and pose human pandemic threats. Most previous studies that have assessed pandemic risk have focused on the role of viral mutations rather than ecological factors. Paul Wikramaratna et al. (pp. 10767–10772) report that the main barriers preventing the emergence of highly pathogenic strains are imposed by the immunity of bird populations to related strains rather than the ability of viruses to acquire the necessary mutations. The authors developed a model to study the evolution of flu viruses in domestic and wild bird species with various lifespans. The model used data from a large-scale study of the prevalence of different flu viruses in European birds and focused on the competition between highly pathogenic and less pathogenic strains. The results suggest that highly pathogenic strains emerge more regularly in short-lived species than in long-lived species due to relatively higher population turnover rates. Moreover, increased contact between species with different lifespans may promote the emergence of virulent strains that were previously suppressed. According to the authors, farming practices that bring short-lived birds such as domestic ducks into close contact with longer-lived wildfowl might contribute to outbreaks of highly pathogenic strains. — J.W.