Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree

Abstract We describe the rate and spectrum of spontaneous mutations for the social amoeba Dictyostelium discoideum, a key model organism in molecular, cellular, evolutionary and developmental biology. Whole-genome sequencing of 37 mutation accumulation lines of D. discoideum after an average of 1,500 cell divisions yields a base-substitution mutation rate of 2.47 × 10−11 per site per generation, substantially lower than that of most eukaryotic and prokaryotic organisms, and of the same order of magnitude as in the ciliates Paramecium tetraurelia and Tetrahymena thermophila. Known for its high genomic AT content and abundance of simple sequence repeats, we observe that base-substitution mutations in D. discoideum are highly A/T biased. This bias likely contributes both to the high genomic AT content and to the formation of simple sequence repeats in the AT-rich genome of Dictyostelium discoideum. In contrast to the situation in other surveyed unicellular eukaryotes, indel rates far exceed the base-substitution mutation rate in this organism with a high proportion of 3n indels, particularly in regions without simple sequence repeats. Like ciliates, D. discoideum has a large effective population size, reducing the power of random genetic drift, magnifying the effect of selection on replication fidelity, in principle allowing D. discoideum to evolve an extremely low base-substitution mutation rate.

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Low Base-Substitution Mutation Rate in the Germline Genome of the CiliateTetrahymena thermophil

Genome Biology and Evolution ◽

10.1093/gbe/evw223 ◽

2016 ◽

pp. evw223 ◽

Cited By ~ 3

Author(s):

Hongan Long ◽

David J. Winter ◽

Allan Y.-C. Chang ◽

Way Sung ◽

Steven H. Wu ◽

...

Keyword(s):

Mutation Rate ◽

Base Substitution ◽

Substitution Mutation

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Low base-substitution mutation rate in the germline genome of the ciliate Tetrahymena thermophila

10.1101/025536 ◽

2015 ◽

Author(s):

Hongan Long ◽

David J. Winter ◽

Allan Y.-C Chang ◽

Way Sung ◽

Steven H. Wu ◽

...

Keyword(s):

Mutation Rate ◽

Tetrahymena Thermophila ◽

Mutation Rates ◽

Base Substitution ◽

Paramecium Tetraurelia ◽

Epigenetic Factors ◽

Detection Approach ◽

Evolution Experiment ◽

Substitution Mutations ◽

Substitution Mutation

AbstractMutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. thermophila has a germline base-substitution mutation rate of 7.61 × 10−12 per site, per cell division, which is consistent with the low base-substitution mutation rate in P. tetraurelia. Over the course of the evolution experiment, genomic exclusion lines derived from the MA lines experienced a fitness decline that cannot be accounted for by germline base-substitution mutations alone, suggesting that other genetic or epigenetic factors must be involved. Because selection can only operate to reduce mutation rates based upon the “visible” mutational load, asexual reproduction with a transcriptionally silent germline may allow ciliates to evolve extremely low germline mutation rates.

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