Quantifying microbial fitness in high-throughput experiments DOI Open Access
Justus Wilhelm Fink, Michael Manhart

Опубликована: Дек. 9, 2024

Few concepts are as central to evolution is fitness, and yet the quantification of fitness often ambiguous. In particular, high-throughput experiments measure mutant in microbes increasingly common but vary widely their definitions which makes results difficult compare. What consequences these different statistics, there a best way quantify given context? Here we systematize set possible statistics according following three choices: 1) encoding relative abundance (e.g., transforming by log or logit function), 2) time scale over change abundance, 3) choice reference subpopulation for calculating bulk competition experiments, such those using DNA-barcoded mutants. We show that choices can lead significantly interpretations affecting magnitude effects, presence epistasis, even ranking across This confound predictions evolutionary dynamics gene functions. Altogether our demonstrate importance consistent reproducible experiments.

Язык: Английский

Epistasis-mediated compensatory evolution in a fitness landscape with adaptational tradeoffs DOI Creative Commons
Suman G. Das, Muhittin Mungan, Joachim Krug

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(15)

Опубликована: Апрель 11, 2025

The evolutionary adaptation of an organism to a stressful environment often comes at the cost reduced fitness. For example, resistance antimicrobial drugs frequently reduces growth rate in drug-free environment. This can be compensated without loss by mutations secondary sites when evolves again stress-free Here, we analytically and numerically study evolution on simple model fitness landscape show that compensatory occur even presence stress need for sites. Fitness depends two phenotypes—the null-fitness defined as absence stress, level stress. Mutations universally exhibit antagonistic pleiotropy between phenotypes, is they increase while decreasing null-fitness. Initial this occurs smooth region with rapid accumulation concurrent decrease followed second, slower phase exhibiting partial recovery second rugged part involves exchange high-cost low-cost ones. process, which call compensation, result changing epistatic interactions genotype progresses. provides general lessons about tempo mode under universal specific implications drug evolution.

Язык: Английский

Процитировано

0
Quantifying microbial fitness in high-throughput experiments DOI Open Access
Justus Wilhelm Fink, Michael Manhart

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 20, 2024

Few concepts are as central to evolution is fitness, and yet the quantification of fitness often ambiguous. In particular, high-throughput experiments measure mutant in microbes increasingly common but vary widely their definitions which makes results difficult compare. What consequences these different statistics, there a best way quantify given context? Here we systematize set possible statistics according following three choices: 1) encoding relative abundance (e.g., transforming by log or logit function), 2) time scale over change abundance, 3) choice reference subpopulation for calculating bulk competition experiments, such those using DNA-barcoded mutants. We show that choices can lead significantly interpretations affecting magnitude effects, presence epistasis, even ranking across This confound predictions evolutionary dynamics gene functions. Altogether our demonstrate importance consistent reproducible experiments.

Язык: Английский

Процитировано

1
Quantifying microbial fitness in high-throughput experiments DOI Open Access
Justus Wilhelm Fink, Michael Manhart

Опубликована: Дек. 9, 2024

Few concepts are as central to evolution is fitness, and yet the quantification of fitness often ambiguous. In particular, high-throughput experiments measure mutant in microbes increasingly common but vary widely their definitions which makes results difficult compare. What consequences these different statistics, there a best way quantify given context? Here we systematize set possible statistics according following three choices: 1) encoding relative abundance (e.g., transforming by log or logit function), 2) time scale over change abundance, 3) choice reference subpopulation for calculating bulk competition experiments, such those using DNA-barcoded mutants. We show that choices can lead significantly interpretations affecting magnitude effects, presence epistasis, even ranking across This confound predictions evolutionary dynamics gene functions. Altogether our demonstrate importance consistent reproducible experiments.

Язык: Английский

Процитировано

1
Massively parallel experimental interrogation of natural variants in ancient signaling pathways reveals both purifying selection and local adaptation DOI Creative Commons
José Aguilar-Rodríguez, Jean C. C. Vila,

Shi-An A. Chen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 31, 2024

Abstract The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are mostly neutral or have functional effects. We address this question by directly mapping the fitness effects over 9,000 natural Ras/PKA and TOR/Sch9 pathways—key regulators cell proliferation eukaryotes—across four conditions Saccharomyces cerevisiae . While many our assay, order 3,500 exhibited significant These non-neutral tend to be missense affect conserved, more densely packed, less solvent-exposed protein regions. They also typically younger, occur at lower frequencies, often found heterozygous states, suggesting they subject purifying selection. A substantial fraction showing strong experiments, however, is present high frequencies population. show signs local adaptation as specifically domesticated strains adapted human-made environments. Our findings support view that while neutral, proportion adaptive consequences driven into positive This study highlights potential explore genome scale quantitative measurements laboratory, bridging gap between genetics genomics understand evolutionary dynamics wild.

Язык: Английский

Процитировано

0
Quantifying microbial fitness in high-throughput experiments DOI Open Access
Justus Wilhelm Fink, Michael Manhart

Опубликована: Дек. 9, 2024

Few concepts are as central to evolution is fitness, and yet the quantification of fitness often ambiguous. In particular, high-throughput experiments measure mutant in microbes increasingly common but vary widely their definitions which makes results difficult compare. What consequences these different statistics, there a best way quantify given context? Here we systematize set possible statistics according following three choices: 1) encoding relative abundance (e.g., transforming by log or logit function), 2) time scale over change abundance, 3) choice reference subpopulation for calculating bulk competition experiments, such those using DNA-barcoded mutants. We show that choices can lead significantly interpretations affecting magnitude effects, presence epistasis, even ranking across This confound predictions evolutionary dynamics gene functions. Altogether our demonstrate importance consistent reproducible experiments.

Язык: Английский

Процитировано

0