Genetic and epigenetic Muller’s ratchet as a mechanism of frailty and morbidity during aging: a demographic genetic model

2019 ◽  
Vol 139 (3) ◽  
pp. 409-420 ◽  
Author(s):  
Hideki Innan ◽  
Reiner Veitia ◽  
Diddahally R. Govindaraju
Keyword(s):  
Genetic Model ◽  
Muller's Ratchet ◽  
Muller’S Ratchet

scholarly journals Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck

PLoS Biology ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. e3001153
Author(s):  
David M. Edwards ◽  
Ellen C. Røyrvik ◽  
Joanna M. Chustecki ◽  
Konstantinos Giannakis ◽  
Robert C. Glastad ◽  
...  
Keyword(s):  
Genetic Model ◽  
Purifying Selection ◽  
Plastid Dna ◽  
Genetic Bottleneck ◽  
Muller's Ratchet ◽  
Organelle Dna ◽  
Comprehensive Theory ◽  
Muller’S Ratchet ◽  
Cell Variance ◽  
Powerful Mechanism

Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) encode vital bioenergetic apparatus, and mutations in these organelle DNA (oDNA) molecules can be devastating. In the germline of several animals, a genetic “bottleneck” increases cell-to-cell variance in mtDNA heteroplasmy, allowing purifying selection to act to maintain low proportions of mutant mtDNA. However, most eukaryotes do not sequester a germline early in development, and even the animal bottleneck remains poorly understood. How then do eukaryotic organelles avoid Muller’s ratchet—the gradual buildup of deleterious oDNA mutations? Here, we construct a comprehensive and predictive genetic model, quantitatively describing how different mechanisms segregate and decrease oDNA damage across eukaryotes. We apply this comprehensive theory to characterise the animal bottleneck with recent single-cell observations in diverse mouse models. Further, we show that gene conversion is a particularly powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the benefit of observed oDNA recombination in diverse organisms which do not sequester animal-like germlines (for example, sponges, corals, fungi, and plants). Genomic, transcriptomic, and structural datasets across eukaryotes support this mechanism for generating beneficial variance without a germline bottleneck. This framework explains puzzling oDNA differences across taxa, suggesting how Muller’s ratchet is avoided in different eukaryotes.

scholarly journals Germline Bottlenecks and the Evolutionary Maintenance of Mitochondrial Genomes

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 2135-2146 ◽  
Author(s):  
Carl T Bergstrom ◽  
Jonathan Pritchard
Keyword(s):  
Equilibrium Distribution ◽  
Genetic Model ◽  
Mutation Rates ◽  
Mitochondrial Genomes ◽  
Uniparental Inheritance ◽  
Small Populations ◽  
Deleterious Mutations ◽  
Muller's Ratchet ◽  
Large Populations ◽  
Muller’S Ratchet

Abstract Several features of the biology of mitochondria suggest that mitochondria might be susceptible to Muller's ratchet and other forms of evolutionary degradation: Mitochondria have predominantly uniparental inheritance, appear to be nonrecombining, and have high mutation rates producing significant deleterious variation. We demonstrate that the persistence of mitochondria may be explained by recent data that point to a severe “bottleneck” in the number of mitochondria passing through the germline in humans and other mammals. We present a population-genetic model in which deleterious mutations arise within individual mitochondria, while selection operates on assemblages of mitochondria at the level of their eukaryotic hosts. We show that a bottleneck increases the efficacy of selection against deleterious mutations by increasing the variance in fitness among eukaryotic hosts. We investigate both the equilibrium distribution of deleterious variation in large populations and the dynamics of Muller's ratchet in small populations. We find that in the absence of the ratchet, a bottleneck leads to improved mitochondrial performance and that, over a longer time scale, a bottleneck acts to slow the progression of the ratchet.

Muller’s ratchet of the Y chromosome with gene conversion

Genetics ◽  
2021 ◽  
Author(s):  
Takahiro Sakamoto ◽  
Hideki Innan
Keyword(s):  
Gene Duplication ◽  
Gene Conversion ◽  
Y Chromosome ◽  
Conversion Rate ◽  
Single Copy ◽  
Duplicated Genes ◽  
Fitness Effect ◽  
Muller's Ratchet ◽  
Y Chromosomes ◽  
Muller’S Ratchet

Abstract Muller’s ratchet is a process in which deleterious mutations are fixed irreversibly in the absence of recombination. The degeneration of the Y chromosome, and the gradual loss of its genes, can be explained by Muller’s ratchet. However, most theories consider single-copy genes, and may not be applicable to Y chromosomes, which have a number of duplicated genes in many species, which are probably undergoing concerted evolution by gene conversion. We developed a model of Muller’s ratchet to explore the evolution of the Y chromosome. The model assumes a non-recombining chromosome with both single-copy and duplicated genes. We used analytical and simulation approaches to obtain the rate of gene loss in this model, with special attention to the role of gene conversion. Homogenization by gene conversion makes both duplicated copies either mutated or intact. The former promotes the ratchet, and the latter retards, and we ask which of these counteracting forces dominates under which conditions. We found that the effect of gene conversion is complex, and depends upon the fitness effect of gene duplication. When duplication has no effect on fitness, gene conversion accelerates the ratchet of both single-copy and duplicated genes. If duplication has an additive fitness effect, the ratchet of single-copy genes is accelerated by gene duplication, regardless of the gene conversion rate, whereas gene conversion slows the degeneration of duplicated genes. Our results suggest that the evolution of the Y chromosome involves several parameters, including the fitness effect of gene duplication by increasing dosage and gene conversion rate.

Amazon molly and Muller's ratchet

Nature ◽  
1995 ◽  
Vol 375 (6527) ◽  
pp. 111-112 ◽  
Author(s):  
Leo W. Beukeboom ◽  
Rolf P. Weinzierl ◽  
Nico K. Michiels
Keyword(s):  
Muller's Ratchet ◽  
Amazon Molly ◽  
Muller’S Ratchet

scholarly journals Drastic Fitness Loss in Human Immunodeficiency Virus Type 1 upon Serial Bottleneck Events

1999 ◽  
Vol 73 (4) ◽  
pp. 2745-2751 ◽  
Author(s):  
Eloisa Yuste ◽  
Sonsoles Sánchez-Palomino ◽  
Concha Casado ◽  
Esteban Domingo ◽  
Cecilio López-Galíndez
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Field Isolate ◽  
Plaque Assay ◽  
Muller's Ratchet ◽  
Immunodeficiency Virus ◽  
Muller’S Ratchet ◽  
Hiv 1

ABSTRACT Muller’s ratchet predicts fitness losses in small populations of asexual organisms because of the irreversible accumulation of deleterious mutations and genetic drift. This effect should be enhanced if population bottlenecks intervene and fixation of mutations is not compensated by recombination. To study whether Muller’s ratchet could operate in a retrovirus, 10 biological clones were derived from a human immunodeficiency virus type 1 (HIV-1) field isolate by MT-4 plaque assay. Each clone was subjected to 15 plaque-to-plaque passages. Surprisingly, genetic deterioration of viral clones was very drastic, and only 4 of the 10 initial clones were able to produce viable progeny after the serial plaque transfers. Two of the initial clones stopped forming plaques at passage 7, two others stopped at passage 13, and only four of the remaining six clones yielded infectious virus. Of these four, three displayed important fitness losses. Thus, despite virions carrying two copies of genomic RNA and the system displaying frequent recombination, HIV-1 manifested a drastic fitness loss as a result of an accentuation of Muller’s ratchet effect.

scholarly journals Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet.

1992 ◽  
Vol 89 (13) ◽  
pp. 6015-6019 ◽  
Author(s):  
E. Duarte ◽  
D. Clarke ◽  
A. Moya ◽  
E. Domingo ◽  
J. Holland
Keyword(s):  
Rna Virus ◽  
Muller's Ratchet ◽  
Muller’S Ratchet

scholarly journals A stochastic model for a single click of Muller's ratchet

2010 ◽  
Vol 264 (4) ◽  
pp. 1120-1132 ◽  
Author(s):  
D. Waxman ◽  
L. Loewe
Keyword(s):  
Stochastic Model ◽  
Muller's Ratchet ◽  
Muller’S Ratchet
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