Mutational Meltdown in Primary Endosymbionts: Selection Limits Muller's Ratchet

AbstractAsexual populations are expected to accumulate deleterious mutations through a process known as Muller’s Ratchet. Lynch, Gabriel, and colleagues have proposed that the Ratchet eventually results in a vicious cycle of mutation accumulation and population decline that drives populations to extinction. They called this phenomenon mutational meltdown. Here, we analyze the meltdown using a multitype branching process model where, in the presence of mutation, populations are doomed to extinction. We find that extinction occurs more quickly in small populations, experiencing a high deleterious mutation rate, and mutations with more severe deleterious effects. The effects of mutational parameters on extinction time in doomed populations differ from those on the severity of Muller’s Ratchet in populations of constant size. We also 1nd that mutational meltdown, although it does occur in our model, does not determine extinction time. Rather, extinction time is determined by the expected impact of deleterious mutations on fitness.

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Spike protein mutational landscape in India: Could Muller’s ratchet be a future game-changer for COVID-19?

10.1101/2020.08.18.255570 ◽

2020 ◽

Cited By ~ 1

Author(s):

Rachana Banerjee ◽

Kausik Basak ◽

Anamika Ghosh ◽

Vyshakh Rajachandran ◽

Kamakshi Sureka ◽

...

Keyword(s):

Mutation Rate ◽

Evolutionary Dynamics ◽

Population Genomics ◽

Spike Protein ◽

Fatality Rate ◽

Indian States ◽

Continuous Increase ◽

Muller's Ratchet ◽

Muller’S Ratchet ◽

Mutational Meltdown

AbstractThe dire need of effective preventive measures and treatment approaches against SARS-CoV-2 virus, causing COVID-19 pandemic, calls for an in-depth understanding of its evolutionary dynamics with attention to specific geographic locations, since lockdown and social distancing to prevent the virus spread could lead to distinct localized dynamics of virus evolution within and between countries owing to different environmental and host-specific selection pressures. To decipher any correlation between SARS-CoV-2 evolution and its epidemiology in India, we studied the mutational diversity of spike glycoprotein, the key player for the attachment, fusion and entry of virus to the host cell. For this, we analyzed the sequences of 630 Indian isolates as available in GISAID database till June 07, 2020, and detected the spike protein variants to emerge from two major ancestors – Wuhan-Hu-1/2019 and its D614G variant. Average stability of the docked spike protein – host receptor (S-R) complexes for these variants correlated strongly (R2=0.96) with the fatality rates across Indian states. However, while more than half of the variants were found unique to India, 67% of all variants showed lower stability of S-R complex than the respective ancestral variants, indicating a possible fitness loss in recently emerged variants, despite a continuous increase in mutation rate. These results conform to the sharply declining fatality rate countrywide (>7-fold during April 11 – June 28, 2020). Altogether, while we propose the potential of S-R complex stability to track disease severity, we urge an immediate need to explore if SARS-CoV-2 is approaching mutational meltdown in India.Author summaryEpidemiological features are intricately linked to evolutionary diversity of rapidly evolving pathogens, and SARS-CoV-2 is no exception. Our work suggests the potential of average stability of complexes formed by the circulating spike mutational variants and the human host receptor to track the severity of SARS-CoV-2 infection in a given region. In India, the stability of these complexes for recent variants tend to decrease relative to their ancestral ones, following countrywide declining fatality rate, in contrast to an increasing mutation rate. We hypothesize such a scenario as nascent footprints of Muller’s ratchet, proposing large-scale population genomics study for its validation, since this understanding could lead to therapeutic approaches for facilitating mutational meltdown of SARS-CoV-2, as experienced earlier for influenza A virus.

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The accumulation of deleterious genes in a population—Muller's Ratchet

Theoretical Population Biology ◽

10.1016/0040-5809(78)90027-8 ◽

1978 ◽

Vol 14 (2) ◽

pp. 251-267 ◽

Cited By ~ 302

Author(s):

John Haigh

Keyword(s):

Muller's Ratchet ◽

Muller’S Ratchet ◽

Deleterious Genes

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Muller’s ratchet of the Y chromosome with gene conversion

Genetics ◽

10.1093/genetics/iyab204 ◽

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.

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Muller's Ratchet

Encyclopedia of Genetics, Genomics, Proteomics and Informatics ◽

10.1007/978-1-4020-6754-9_10903 ◽

2008 ◽

pp. 1283-1284

Keyword(s):

Muller's Ratchet ◽

Muller’S Ratchet

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Amazon molly and Muller's ratchet

Nature ◽

10.1038/375111c0 ◽

1995 ◽

Vol 375 (6527) ◽

pp. 111-112 ◽

Cited By ~ 1

Author(s):

Leo W. Beukeboom ◽

Rolf P. Weinzierl ◽

Nico K. Michiels

Keyword(s):

Muller's Ratchet ◽

Amazon Molly ◽

Muller’S Ratchet

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

Journal of Virology ◽

10.1128/jvi.73.4.2745-2751.1999 ◽

1999 ◽

Vol 73 (4) ◽

pp. 2745-2751 ◽

Cited By ~ 121

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.

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