Limits of neutral drift: lessons from the in vitro evolution of two ribozymes
Open accessAbstract
The relative contributions of adaptive selection and neutral drift to genetic change are unknown but likely depend on the inherent abundance of functional genotypes in sequence space and how accessible those genotypes are to one another. To better understand the relative roles of selection and drift in evolution, local fitness landscapes for two different RNA ligase ribozymes were examined using a continuous in vitro evolution system under conditions that foster the capacity for neutral drift to mediate genetic change. The exploration of sequence space was accelerated by increasing the mutation rate using mutagenic nucleotide analogs. Drift was encouraged by carrying out evolution within millions of separate compartments to exploit the founder effect. Deep sequencing of individuals from the evolved populations revealed that the distribution of genotypes did not escape the starting local fitness peak, remaining clustered around the sequence used to initiate evolution. This is consistent with a fitness landscape where high-fitness genotypes are sparse and well isolated, and suggests, at least in this context, that neutral drift alone is not a primary driver of genetic change. Neutral drift does, however, provide a repository of genetic variation upon which adaptive selection can act.
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Extensive studies of the fitness landscapes of various functional RNAs have shown mostly isolated, sharp peaks with distinct structural motifs linked by generally unfavorable paths of mutation.
“extensive studies of the fitness landscapes of various functional RNAs have shown mostly isolated, sharp peaks with distinct structural motifs linked by generally unfavorable paths of mutation [140–142].”
From The RNA world as a model system to study the origin of life (2015) · cites this paper as [142]
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- Authors
- Petrie, K. L., & Joyce, G. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Joyce, Gerald F.
- Venue
- Journal of Molecular Evolution
- Published
- 2014-08-26
- Volume
- 79
- Issue
- 3-4
- Pages
- 75-90
- ISSN
- 0022-2844 (ISSN-L)
- 1432-1432
- PMC
- PMC4185262
- OpenAlex
- W1964634283
- Cited by
- 27
- References
- 50
- Citations by year
- 2026: 2 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 8 · 2016: 3 · 2015: 4
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Evolution (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM065130, T32GM080209)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Keywords
- neutral drift, positive selection, in vitro evolution, fitness landscape, sequence space exploration, founder effect, genetic variation, RNA evolution
- MeSH terms
- Base Sequence, Genotype, Models, Genetic, Molecular Sequence Data, Nucleic Acid Conformation, RNA, Catalytic, Sequence Analysis, DNA, Founder Effect, Evolution, Molecular, Genetic Drift, Genetic Fitness, Mutation Rate
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