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Surviving the ratchet: Modelling deleterious mutations in asexual populations
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution. (Otto Berg)
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

One of the most unforgiving processes in nature is that of Muller's ratchet, a seemingly irreversible accumulation of deleterious mutations that all organisms have to deal with or face extinction. The most obvious way to avoid fitness collapse is recombination, though asexual populations usually do not have the luxury of recombining freely.  With the aid of computational and mathematical models, we have studied other situations where this threat is averted and the organism can survive the ratchet.

The results show that a ratchet where all mutations have the same deleterious fitness effect is very effectively stalled for large effects. However, if mutations are allowed to have a broad range of effects, the fitness-loss rate can be substantial even with the same mean effect as the one-type ratchet, but we have  identified parameter regions where even the broad-range effects are effectively stopped.

The fitness-loss from a ratchet is very sensitive to the mutation rate and a mutation that increases the mutation rate (mutator) can easily start an otherwise stalled ratchet. Large effect mutators are heavily counter-selected, but smaller mutators can spread in the population. They can be stopped by reversals (antimutators), but even if the mutation rate is equilibrated in this way, there will be large fluctuations in mutation rate and even larger in the fitness-loss rate due to the feedback amplification in their coupling.   

Another way of preventing the ratchet is by reversal of the deleterious mutations themselves through back-mutations or compensatory mutations. The rate required to stop the ratchet using only back-mutations before the fitness collapses is very large. A detailed comparison between the deleterious mutations in the ratchet and in a sexual population was made and the difference was found to be greatest for large populations with large genomes.

There are obviously many ways to survive the ratchet, but even more ways to drive a species to extinction by enhancing and speeding up the ratchet. By modelling and testing the ratchet for numerous different situations, we show the effects of some of these threats and benefits.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 38 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 846
Keyword [en]
Theoretical biology, Population genetics, Stochastic modelling, Genome evolution, Muller's Ratchet
National Category
Genetics Microbiology Biological Sciences
Research subject
Biology with specialization in Molecular Evolution
Identifiers
URN: urn:nbn:se:uu:diva-157897ISBN: 978-91-554-8137-7 (print)OAI: oai:DiVA.org:uu-157897DiVA: diva2:436989
Public defence
2011-10-07, Ekmansalen, Evolutionsbiologiskt centrum, EBC Norbyvägen 14, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2011-09-15 Created: 2011-08-26 Last updated: 2011-11-03Bibliographically approved
List of papers
1. Mutational interference and the progression of Muller's ratchet when mutations have a broad range of deleterious effects
Open this publication in new window or tab >>Mutational interference and the progression of Muller's ratchet when mutations have a broad range of deleterious effects
2007 (English)In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 177, no 2, 971-986 p.Article in journal (Refereed) Published
Abstract [en]

Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet. This process has been described in the literature mostly for the case where all mutations are assumed to have the same effect on fitness. In the more realistic situation, deleterious mutations will affect fitness with a wide range of effects, from almost neutral to lethal. To elucidate the behavior of the ratchet in this more realistic case, simulations were carried out in a number of models, one where all mutations have the same effect on selection [one-dimensional (1D) model], one where the deleterious mutations can be divided into two groups with different selective effects [two-dimensional (2D) model], and finally one where the deleterious effects are distributed. The behavior of these models suggests that deleterious mutations can be classified into three different categories, such that the behavior of each can be described in a straightforward way. This makes it possible to predict the ratchet rate for an arbitrary distribution of fitness effects using the results for the well-studied 1D model with a single selection coefficient. The description was tested and shown to work well in simulations where selection coefficients are derived from an exponential distribution.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-14378 (URN)10.1534/genetics.107.073791 (DOI)000250657800027 ()17720933 (PubMedID)
Available from: 2008-01-30 Created: 2008-01-30 Last updated: 2017-12-11Bibliographically approved
2. Kick-Starting the Ratchet: The Fate of Mutators in an Asexual Population
Open this publication in new window or tab >>Kick-Starting the Ratchet: The Fate of Mutators in an Asexual Population
2011 (English)In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 187, no 4, 1129-1137 p.Article in journal (Refereed) Published
Abstract [en]

Muller's ratchet operates in asexual populations without intergenomic recombination. In this case, deleterious mutations will accumulate and population fitness will decline over time, possibly endangering the survival of the species. Mutator mutations, i.e., mutations that lead to an increased mutation rate, will play a special role for the behavior of the ratchet. First, they are part of the ratchet and can come to dominance through accumulation in the ratchet. Second, the fitness-loss rate of the ratchet is very sensitive to changes in the mutation rate and even a modest increase can easily set the ratchet in motion. In this article we simulate the interplay between fitness loss from Muller's ratchet and the evolution of the mutation rate from the fixation of mutator mutations. As long as the mutation rate is increased in sufficiently small steps, an accelerating ratchet and eventual extinction are inevitable. If this can be countered by antimutators, i.e., mutations that reduce the mutation rate, an equilibrium can be established for the mutation rate at some level that may allow survival. However, the presence of the ratchet amplifies fluctuations in the mutation rate and, even at equilibrium, these fluctuations can lead to dangerous bursts in the ratchet. We investigate the timescales of these processes and discuss the results with reference to the genome degradation of the aphid endosymbiont Buchnera aphidicola.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-152903 (URN)10.1534/genetics.110.124818 (DOI)000289277300017 ()21288878 (PubMedID)
Available from: 2011-05-03 Created: 2011-05-03 Last updated: 2017-12-11Bibliographically approved
3. Mutation load in sexual and asexual populations: Effects of distributed selection coefficients on stationary fitness and rate of fitness loss
Open this publication in new window or tab >>Mutation load in sexual and asexual populations: Effects of distributed selection coefficients on stationary fitness and rate of fitness loss
(English)Manuscript (preprint) (Other academic)
Identifiers
urn:nbn:se:uu:diva-157896 (URN)
Available from: 2011-08-26 Created: 2011-08-26 Last updated: 2011-11-03

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