Kiefl
Evan
Kiefl
Evan
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ArticleStructure-informed microbial population genetics elucidate selective pressures that shape protein evolution(American Association for the Advancement of Science, 2023-02-22) Kiefl, Evan ; Esen, Ozcan C. ; Miller, Samuel E. ; Kroll, Kourtney L. ; Willis, Amy D. ; Rappé, Michael S. ; Pan, Tao ; Eren, A. MuratComprehensive sampling of natural genetic diversity with metagenomics enables highly resolved insights into the interplay between ecology and evolution. However, resolving adaptive, neutral, or purifying processes of evolution from intrapopulation genomic variation remains a challenge, partly due to the sole reliance on gene sequences to interpret variants. Here, we describe an approach to analyze genetic variation in the context of predicted protein structures and apply it to a marine microbial population within the SAR11 subclade 1a.3.V, which dominates low-latitude surface oceans. Our analyses reveal a tight association between genetic variation and protein structure. In a central gene in nitrogen metabolism, we observe decreased occurrence of nonsynonymous variants from ligand-binding sites as a function of nitrate concentrations, revealing genetic targets of distinct evolutionary pressures maintained by nutrient availability. Our work yields insights into the governing principles of evolution and enables structure-aware investigations of microbial population genetics.
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ArticleA cryptic plasmid is among the most numerous genetic elements in the human gut(Elsevier, 2024-02-29) Fogarty, Emily C. ; Schechter, Matthew S. ; Lolans, Karen ; Sheahan, Madeline L. ; Veseli, Iva A. ; Moore, Ryan M. ; Kiefl, Evan ; Moody, Thomas ; Rice, Phoebe A. ; Yu, Michael K. ; Mimee, Mark ; Chang, Eugene B. ; Ruscheweyh, Hans-Joachim ; Sunagawa, Shinichi ; McLellan, Sandra L. ; Willis, Amy D. ; Comstock, Laurie E. ; Eren, A. MuratPlasmids are extrachromosomal genetic elements that often encode fitness-enhancing features. However, many bacteria carry “cryptic” plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes and is 14 times as numerous as crAssphage, currently established as the most abundant extrachromosomal genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is monoclonal in most individuals, likely due to the priority effect of the version first acquired, often from one’s mother. pBI143 can transfer between Bacteroidales, and although it does not appear to impact bacterial host fitness in vivo, it can transiently acquire additional genetic content. We identified important practical applications of pBI143, including its use in identifying human fecal contamination and its potential as an alternative approach to track human colonic inflammatory states.