• Investigating the influence of environment on the evolution of Hsp90 using comprehensive fitness maps [preprint]

      Flynn, Julia M.; Rossouw, Ammeret; Cote-Hammarlof, Pamela A.; Fragata, Ines; Mavor, David; Hollins, Carl III; Bank, Claudia; Bolon, Daniel N. (2019-12-09)
      Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered budding yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard laboratory conditions and under five stress conditions (elevated temperature, nitrogen starvation, elevated salinity, high ethanol concentration, and oxidative stress caused by diamide). To our knowledge these are the largest comprehensive fitness maps of point mutant growth effects that have been determined. The growth effects of many variants differed between each of the conditions, indicating that environmental conditions can have a large impact on the evolution of Hsp90. Multiple variants provided growth advantages relative to wildtype Hsp90 under individual conditions, however these variants tended to exhibit growth defects in other environments. The diversity of Hsp90 sequences observed in extant eukaryotes preferentially contain amino acid variants that supported robust growth under all tested conditions. Thus, rather than favoring substitutions in individual conditions, the long-term selective pressure on Hsp90 may have been that of fluctuating environments, leading to robustness under a variety of conditions.
    • Race, Ethnicity, Income Concentration and 10-Year Change in Urban Greenness in the United States

      Casey, Joan A.; James, Peter; Cushing, Lara; Jesdale, William M.; Morello-Frosch, Rachel (2017-12-10)
      Background: Cross-sectional studies suggest urban greenness is unequally distributed by neighborhood demographics. However, the extent to which inequalities in greenness have changed over time remains unknown. Methods: We estimated 2001 and 2011 greenness using Moderate-resolution Imaging Spectroradiometer (MODIS) satellite-derived normalized difference vegetative index (NDVI) in 59,483 urban census tracts in the contiguous U.S. We fit spatial error models to estimate the association between baseline census tract demographic composition in 2000 and (1) 2001 greenness and (2) change in greenness between 2001 and 2011. Results: In models adjusted for population density, climatic factors, housing tenure, and Index of Concentration at the Extremes for income (ICE), an SD increase in percent White residents (a 30% increase) in 2000 was associated with 0.021 (95% CI: 0.018, 0.023) higher 2001 NDVI. We observed a stepwise reduction in 2001 NDVI with increased concentration of poverty. Tracts with a higher proportion of Hispanic residents in 2000 lost a small, statistically significant amount of greenness between 2001 and 2011 while tracts with higher proportions of Whites experienced a small, statistically significant increase in greenness over the same period. Conclusions: Census tracts with a higher proportion of racial/ethnic minorities, compared to a higher proportion of White residents, had less greenness in 2001 and lost more greenness between 2001 and 2011. Policies are needed to increase greenness, a health-promoting neighborhood asset, in disadvantaged communities.