Santa Fe Institute

About: Santa Fe Institute is a nonprofit organization based out in Santa Fe, New Mexico, United States. It is known for research contribution in the topics: Population & Context (language use). The organization has 558 authors who have published 4558 publications receiving 396015 citations. The organization is also known as: SFI.

Metagenomic evidence for taxonomic dysbiosis and functional imbalance in the gastrointestinal tracts of children with cystic fibrosis.

Abstract: Cystic fibrosis (CF) results in inflammation, malabsorption of fats and other nutrients, and obstruction in the gastrointestinal (GI) tract, yet the mechanisms linking these disease manifestations to microbiome composition remain largely unexplored. Here we used metagenomic analysis to systematically characterize fecal microbiomes of children with and without CF, demonstrating marked CF-associated taxonomic dysbiosis and functional imbalance. We further showed that these taxonomic and functional shifts were especially pronounced in young children with CF and diminished with age. Importantly, the resulting dysbiotic microbiomes had significantly altered capacities for lipid metabolism, including decreased capacity for overall fatty acid biosynthesis and increased capacity for degrading anti-inflammatory short-chain fatty acids. Notably, these functional differences correlated with fecal measures of fat malabsorption and inflammation. Combined, these results suggest that enteric fat abundance selects for pro-inflammatory GI microbiota in young children with CF, offering novel strategies for improving the health of children with CF-associated fat malabsorption.

Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

Abstract: A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median=4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.

Megafauna extinction, tree species range reduction, and carbon storage in Amazonian forests

Abstract: During the Late Pleistocene and early Holocene 59 species of South American megafauna went extinct. Their extinction potentially triggered population declines of large-seeded tree species dispersed by the large-bodied frugivores with which they co-evolved, a theory first proposed by Janzen and Martin (1982). We tested this hypothesis using species range maps for 257 South American tree species, comparing 63 species thought to be primarily distributed by megafauna with 194 distributed by other animals. We found a highly significant (p 95% following disperser extinction. A numerical gap dynamic simulations suggests that over a 10 000 yr period following the disperser extinctions, the average convex hull range size of large-seeded tree species decreased by ∼ 31%, while the estimated decrease in population size was ∼ 54%, indicating a likely greater decrease in species population size than indicated by the empirical range patterns. Finally, we found a positive correlation between seed size and wood density of animal-dispersed tree species implying that the Late Pleistocene and early Holocene megafaunal extinctions reduced carbon content in the Amazon by ∼ 1.5 ± 0.7%. In conclusion, we 1) provide some empirical evidence that megafauna distributed fruit species have a smaller mean range size than wind, water or other animal-dispersed species, 2) demonstrate mathematically that such range reductions are expected from megafauna extinctions ca 12 000 yr ago, and 3) illustrate that these extinctions may have reduced the Amazon's carbon storage capacity.

The Rate and Spectrum of Spontaneous Mutations in a Plant RNA Virus

Abstract: Knowing mutation rates and the molecular spectrum of spontaneous mutations is important to understanding how the genetic composition of viral populations evolves. Previous studies have shown that the rate of spontaneous mutations for RNA viruses widely varies between 0.01 and 2 mutations per genome and generation, with plant RNA viruses always occupying the lower side of this range. However, this peculiarity of plant RNA viruses is based on a very limited number of studies. Here we analyze the spontaneous mutational spectrum and the mutation rate of Tobacco etch potyvirus, a model system of positive sense RNA viruses. Our experimental setup minimizes the action of purifying selection on the mutational spectrum, thus giving a picture of what types of mutations are produced by the viral replicase. As expected for a neutral target, we found that transitions and nonsynonymous (including a few stop codons and small deletions) mutations were the most abundant type. This spectrum was notably different from the one previously described for another plant virus. We have estimated that the spontaneous mutation rate for this virus was in the range 10−6−10−5 mutations per site and generation. Our estimates are in the same biological ballpark that previous values reported for plant RNA viruses. This finding gives further support to the idea that plant RNA viruses may have lower mutation rates than their animal counterparts.