Aging and Senescence

Mapping Intimacies ◽

10.1093/oso/9780190687724.003.0004 ◽

2021 ◽

pp. 62-84

Author(s):

Gary C. Howard

Keyword(s):

Natural Selection ◽

Mutation Accumulation

Why do we age? Aging has been an important issue in biology for many decades, and many questions remain unanswered. However, any explanation of aging must agree with Darwin’s theory of natural selection. Genes that benefit fitness early on in an individual’s lifetime will be favored. Ones that hinder fitness early on will be selected against because those individuals will reproduce less successfully. Genes that have an effect later in life (after the reproductive years) are not subject to natural selection. Thus, the force of natural selection is lost later in life. Three key theories have been proposed to explain how aging might have evolved: mutation accumulation theory, antagonistic pleiotrophy, and disposable soma. These three main theories are not mutually exclusive. Finally, is aging simply another disease?

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Selection in a growing bacterial/yeast colony biases results of mutation accumulation experiments

10.1101/2021.04.12.439444 ◽

2021 ◽

Author(s):

Anjali Mahilkar ◽

Sharvari Kemkar ◽

Supreet Saini

Keyword(s):

Natural Selection ◽

Population Size ◽

Effective Population Size ◽

Colony Growth ◽

Mutation Accumulation ◽

Rate Of Change ◽

Raw Material ◽

Effective Population ◽

The Face ◽

Mean Fitness

AbstractMutations provide the raw material for natural selection to act. Therefore, understanding the variety and relative frequency of different type of mutations is critical to understanding the nature of genetic diversity in a population. Mutation accumulation (MA) experiments have been used in this context to estimate parameters defining mutation rates, distribution of fitness effects (DFE), and spectrum of mutations. MA experiments performed with organisms such asDrosophilahave an effective population size of one. However, in MA experiments with bacteria and yeast, a single founder is allowed to grow to a size of a colony (~108). The effective population size in these experiments is of the order of 10. In this scenario, while it is assumed that natural selection plays a minimal role in dictating the dynamics of colony growth and therefore, the MA experiment; this effect has not been tested explicitly. In this work, we simulate colony growth and perform an MA experiment, and demonstrate that selection ensures that, in an MA experiment, fraction of all mutations that are beneficial is over represented by a factor greater than two. The DFE of beneficial and deleterious mutations are accurately captured in an MA experiment. We show that the effect of selection in a growing colony varies non-monotonically and that, in the face of natural selection dictating an MA experiment, estimates of mutation rate of an organism is not trivial. We perform experiments with 160 MA lines ofE. coli, and demonstrate that rate of change of mean fitness is a non-monotonic function of the colony size, and that selection acts differently in different sectors of a growing colony. Overall, we demonstrate that the results of MA experiments need to be revisited taking into account the action of selection in a growing colony.

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Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations

10.1101/095182 ◽

2016 ◽

Author(s):

Zoe June Assaf ◽

Susanne Tilk ◽

Jane Park ◽

Mark L. Siegal ◽

Dmitri A. Petrov

Keyword(s):

Drosophila Melanogaster ◽

Natural Selection ◽

De Novo ◽

Natural Populations ◽

Gc Content ◽

Mutation Accumulation ◽

Sequencing Error ◽

Low Frequencies ◽

Nucleotide Mutation ◽

New Mutations

AbstractMutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on whether we have precise measurements of mutational rates and patterns. Here we explore the rates and patterns of mutations using i) de novo mutations from Drosophila melanogaster mutation accumulation lines and ii) polymorphisms segregating at extremely low frequencies. The first, mutation accumulation (MA) lines, are the product of maintaining flies in tiny populations for many generations, therefore rendering natural selection ineffective and allowing new mutations to accrue in the genome. In addition to generating a novel dataset of sequenced MA lines, we perform a meta-analysis of all published MA studies in D. melanogaster, which allows more precise estimates of mutational patterns across the genome. In the second half of this work, we identify polymorphisms segregating at extremely low frequencies using several publicly available population genomic data sets from natural populations of D. melanogaster. Extremely rare polymorphisms are difficult to detect with high confidence due to the problem of distinguishing them from sequencing error, however a dataset of true rare polymorphisms would allow the quantification of mutational patterns. This is due to the fact that rare polymorphisms, much like de novo mutations, are on average younger and also relatively unaffected by the filter of natural selection. We identify a high quality set of ~70,000 rare polymorphisms, fully validated with resequencing, and use this dataset to measure mutational patterns in the genome. This includes identifying a high rate of multi-nucleotide mutation events at both short (~5bp) and long (~1kb) genomic distances, showing that mutation drives GC content lower in already GC-poor regions, and finding that the context-dependency of the mutation spectrum predicts long-term evolutionary patterns at four-fold synonymous sites. We also show that de novo mutations from independent mutation accumulation experiments display similar patterns of single nucleotide mutation, and match well the patterns of mutation found in natural populations.

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Heterogeneous mutation rates and spectra within and between species of yeast and their hybrids

10.1101/2021.06.04.447117 ◽

2021 ◽

Author(s):

Anna Fijarczyk ◽

Mathieu Hénault ◽

Souhir Marsit ◽

Guillaume Charron ◽

Christian R Landry

Keyword(s):

Growth Rate ◽

Natural Selection ◽

Loss Of Heterozygosity ◽

Genome Sequencing ◽

Mutation Accumulation ◽

Mutation Rates ◽

Interspecific Crosses ◽

Minor Role ◽

Saccharomyces Paradoxus ◽

A Minor

Mutation rates and spectra vary between species and among populations. Hybridization can contribute to this variation but its role remains poorly understood. Estimating mutation rates requires controlled conditions where the effect of natural selection can be minimized. One way to achieve this is through mutation accumulation experiments coupled with genome sequencing. Here we investigate 400 mutation accumulation lines initiated from 11 genotypes spanning intra-lineage, inter-lineage and interspecific crosses of the yeasts Saccharomyces paradoxus and S. cerevisiae, and propagated for 770 generations. We find significant differences in mutation rates and spectra among crosses, which are not related to the level of divergence of parental strains, but are genotype specific. We find that departures from neutrality, differences in growth rate, ploidy and loss of heterozygosity only play a minor role as a source of variation and conclude that unique combinations of parental genotypes drive distinct rates and spectra in some crosses.

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