Biology subjects

Galeota-Sprung, B.

Publications and source records attributed to Galeota-Sprung, B..

7 recordsLinked to original sources

bioRxiv2026

Diploidy alters the path of fluconazole adaptation in C. glabrata

C. glabrata (syn. Nakaseomyces glabratus) is a major fungal pathogen, typically isolated as a haploid. We isolated a spontaneous diploid variant of the type strain CBS138 and performed experimental evolution under fluconazole. At physiologically relevant concentrations of fluconazole, we found that haploids and diploids both acquired PDR1 mutations, as is commonly observed in C. glabrata; diploids additionally acquired heterozygous ERG11 and ERG25 mutations and were more likely to acquire aneuploidies. Despite an ancestral fitness advantage for haploids, after [~]200 generations the highest-fitness clones, as measured in competitive assays with and without fluconazole, were diploid double heterozygotes having nonsynonymous mutations to PDR1 and ERG11 or PDR1 and ERG25. Diploid clones also had higher MICs. These results suggest, in this particular context, an evolvability advantage for diploids. In a follow-up experiment in which we rapidly increased the fluconazole concentration to a very high concentration, haploids and diploids adapted via entirely distinct routes: haploids via co-mutation in ERG3 and CgOSH3, a previously unreported path to fluconazole resistance, and diploids via heterozygous mutation in ERG25 coupled with trisomies of chrF, chrG, and chrI in all sampled clones, and chrC in most sampled clones.

evolutionary biology↗

bioRxiv2024

Directed evolution for cell separation in budding yeast

Natural isolates of the yeast Saccharomyces cerevisiae were evolved under a transfer protocol that selected for cell separation and against clumpy growth. Whole-genome sequencing of haploid populations revealed strong selection to deactivate AMN1, a known regulator of post-mitotic cell separation, as well as multiple instances of loss-of-function mutations on the Rim101 pathway, pointing to a previously unknown role of the Rim101 pathway in regulating cell separation. In diploid populations, we observed repeated large partial deletions of chromosome III caused by fusions of the mating type loci MAT and HMR (Hawthornes deletion) or MAT and HML (Stratherns circle). We measured the spontaneous rate of Hawthornes deletion and found that it is within an order of magnitude of previously measured rates of whole-chromosome aneuploidy. A diploid population in which neither large deletion was detected instead fixed a heterozygous nonsynonymous mutation to the calcium channel CCH1, also pointing to a novel role for this gene in relation to cell separation.

evolutionary biology↗

bioRxiv2021

Changes to the mtDNA copy number during the course of yeast culture growth

We show that the mtDNA copy number in growing cultures of the yeast Saccharomyces cerevisiae increases by a factor of up to 4, being lowest ([~]10 per haploid genome) and stable during rapid fermentative growth, and highest at the end of the respiratory phase. When yeast are grown on glucose, the onset of the mtDNA copy number increase coincides with the early stages of the diauxic shift, and the increase continues through respiration. A lesser yet still substantial copy number increase occurs when yeast are grown on a nonfermentable carbon source, i.e. when there is no diauxic shift. The mtDNA copy number increase during and for some time after the diauxic shift is not driven by an increase in cell size. The copy number increase occurs in both haploid and diploid strains, but is markedly attenuated in a diploid wild isolate that is a ready sporulator. Strain-to-strain differences in mtDNA copy number are least apparent in fermentation and most apparent in late respiration or stationary phase. While changes in mitochondrial morphology and function were previously known to accompany changes in physiological state, it had not been previously shown that the mtDNA copy number changes substantially over time in a clonal growing culture. The mtDNA copy number in yeast is therefore a highly dynamic phenotype.

cell biology↗

bioRxiv2021

Natural selection promotes the evolution of recombination 2: during the selective process

The ubiquity of sex and recombination in nature has eluded unified explanation since the time of Darwin. Conditions that promote the evolution of recombination, broadly defined as any form of genetic mixing, are fairly well understood: it is favored when genomes tend to contain more selectively mismatched combinations of alleles than can be explained by chance alone. Yet, while a variety of theoretical approaches have been put forth to explain why such conditions would prevail in natural populations, each has turned out to be of limited scope and applicability. Here, we show, simply and surprisingly, that natural selection acting on standing heritable variation always creates conditions favoring the evolution of recombination, in expectation. Specifically, we find that, in expectation: 1) the mean selective advantage of recombinants is non-negative, 2) the mean selective advantage of a recombination-competent modifier is non-negative, and 3) the asymptotic frequency of a recombination-competent modifier is close to one and is independent of the strength of selection. Remarkably, these findings are independent of the distribution of genic fitnesses in the standing heritable variation upon which natural selection acts, implying that the source of this variation is immaterial. Taken together, our findings indicate that: 1) the evolution of recombination should be promoted in expectation wherever natural selection is operating, and 2) sex and recombination may have evolved more as a byproduct than as a catalyst of natural selection.

evolutionary biology↗

bioRxiv2020

Natural selection and the advantage of recombination

The ubiquity of sex and recombination in nature is widely viewed as enigmatic, despite an abundance of limited-scope explanations. Natural selection, it seems, should amplify well-matched combinations of genes. Recombination would break up these well-matched combinations and should thus be suppressed. We show, to the contrary, that on average: 1) natural selection amplifies poorly-matched gene combinations and 2) creates time-averaged negative associations in the process. Recombination breaks up these poorly-matched combinations, neutralizes the negative associations, and should thus be passively and universally favored.

evolutionary biology↗

bioRxiv2019

Mutational load and the functional fraction of the human genome

The fraction of the human genome that is functional is a question of both evolutionary and practical importance. Studies of sequence divergence have suggested that the functional fraction of the human genome is likely to be no more than [~]15%. In contrast, the ENCODE project, a systematic effort to map regions of transcription, transcription factor association, chromatin structure, and histone modification, assigned function to 80% of the human genome. In this paper we examine whether and how an analysis based on mutational load might set a limit on the functional fraction. In order to do so, we characterize the distribution of fitness of a large, finite, diploid population at mutation-selection equilibrium. In particular, if mean fitness is [~]1, the fitness of the fittest individual likely to occur cannot be unreasonably high. We find that at equilibrium, the distribution of log fitness has variance nus, where u is the per-base deleterious mutation rate, n is the number of functional sites (and hence incorporates the functional fraction f), and s is the selection coefficient of deleterious mutations. In a large (N = 109) reproducing population, the fitness of the fittest individual likely to exist is [Formula]. These results apply to both additive and recessive fitness schemes. Our approach is different from previous work that compared mean fitness at mutation-selection equilibrium to the fitness of an individual who has no deleterious mutations; we show that such an individual is exceedingly unlikely to exist. We find that the functional fraction is not very likely to be limited substantially by mutational load, and that any such limit, if it exists, depends strongly on the selection coefficients of new deleterious mutations.

evolutionary biology↗

bioRxiv2019

The fitness cost of mismatch repair mutators in Saccharomyces cerevisiae: partitioning the mutational load

Mutational load is the depression in a populations mean fitness that results from the continual influx of deleterious mutations. Here, we directly estimate the mutational load in a population of haploid Saccharomyces cerevisiae that are deficient for mismatch repair. We partition the load in haploids into two components. To estimate the load due to nonlethal mutations, we measure the competitive fitness of hundreds of randomly selected clones from both mismatch repair-deficient and - proficient populations. Computation of the mean clone fitness for the mismatch repair-deficient strain permits an estimation of the nonlethal load, and the histogram of fitness provides an interesting visualization of a loaded population. In a separate experiment, in order to estimate the load due to lethal mutations (i.e. the lethal mutation rate), we manipulate thousands of individual pairs of mother and daughter cells and track their fates. These two approaches yield point estimates for the two contributors to load, and the addition of these estimates is nearly equal to the separately measured short-term competitive fitness deficit for the mismatch repair-deficient strain. This correspondence suggests that there is no need to invoke direct fitness effects to explain the fitness difference between mismatch repair-deficient and - proficient strains. Assays in diploids are consistent with deleterious mutations in diploids tending towards recessivity. These results enhance our understanding of mutational load, a central population genetics concept, and we discuss their implications for the evolution of mutation rates.

evolutionary biology↗