Biology subjects

Kondrashov, A. S.

Publications and source records attributed to Kondrashov, A. S..

11 recordsLinked to original sources

bioRxiv2023

Positive association between alleles at selectively neutral loci

Linkage disequilibrium (LD) is a non-independent distribution of alleles at different loci and might be defined using directional and directionless approaches. While analytical theory is available for directionless LD, analytical theory for directional LD is less developed. In this study we investigated directional LD generated by random drift between two selectively neutral loci. When the sign of LD is determined by the ancestral-derived status of these alleles, its expected value is zero. In contrast, computer simulations show that random drift leads to a tendency of rare, as well as of common, alleles to occur together. This observation is supported by a straightforward analytical argument. If only those generations where both loci are polymorphic are taken into account, the magnitude of the resulting directional LD depends only on Ne. These observations might give an opportunity to directly estimate Ne from the data on genetic variation within a single generation.

genetics↗

bioRxiv2022

Extended family with germline pathogenic variant in polymerase delta provides strong evidence for recessive effect of proofreading inactivation

Mutational processes in germline and in somatic cells are vastly different, and it remains unclear how the same genetic background affects somatic and transmissible mutations. Here, we estimate the impact of an inherited pathogenic variant in the exonuclease domain of polymerase delta (Pol{delta}) on somatic and germline mutational processes and cancer development. In germline cells and in non-cancer somatic cells, the POLD1 L474P variant increases the mutation burden only slightly, contributing [~]11.8% and [~]14.7% of mutations respectively, although it strongly distorts the mutational spectra. By contrast, tumors developed by carriers of inherited pathogenic variants in POLD1 harbor a DNA rearrangement that results in a homozygous state of the pathogenic variant, leading to an extremely high mutation rate. Thus, mutations in both alleles of POLD1 gene are required for strong increase in mutation rate suggesting recessiveness of Pold{delta} proofreading. These results show a similar role of Pol{delta} in germline and somatic replication, and, together with previous findings, illustrate the important differences between Pol{delta} and Pol{varepsilon} in the disruption of their replication fidelity.

genetics↗

bioRxiv2021

Complex fitness landscape shapes variation in a hyperpolymorphic species

It is natural to assume that patterns of genetic variation in hyperpolymorphic species can reveal large-scale properties of the fitness landscape that are hard to detect by studying species with ordinary levels of genetic variation1,2. Here, we study such patterns in a fungus Schizophyllum commune, the most polymorphic species known3. Throughout the genome, short-range linkage disequilibrium caused by attraction of rare alleles is higher between pairs of nonsynonymous than of synonymous sites. This effect is especially pronounced for pairs of sites that are located within the same gene, especially if a large fraction of the gene is covered by haploblocks, genome segments where the gene pool consists of two highly divergent haplotypes, which is a signature of balancing selection. Haploblocks are usually shorter than 1000 nucleotides, and collectively cover about 10% of the S. commune genome. LD tends to be substantially higher for pairs of nonsynonymous sites encoding amino acids that interact within the protein. There is a substantial correlation between LDs at the same pairs of nonsynonymous sites in the USA and the Russian populations. These patterns indicate that selection in S. commune involves positive epistasis due to compensatory interactions between nonsynonymous alleles. When less polymorphic species are studied, analogous patterns can be detected only through interspecific comparisons.

evolutionary biology↗

bioRxiv2019

Rapid accumulation of mutations in growing mycelia of a hypervariable fungus Schizophyllum commune

The number of mutations that occur per nucleotide per generation varies between species by several orders of magnitude. In multicellular eukaryotes, the per generation mutation rate depends both on the per cell division mutation rate and on the number of germline cell divisions per generation. In a range of species, from fungi to humans, the number of germline cell divisions is lower than that of somatic cells, reducing the mutation burden on the offspring. The basidiomycete Schizophyllum commune has the highest level of genetic polymorphism known among eukaryotes. In a previous study, it was also found to have a high per generation mutation rate, probably contributing to its high polymorphism. However, this rate has been measured only in a breeding experiment on Petri dishes, and it is unclear how this result translates to natural populations. Here, we used an experimental design that measures the rate of accumulation of de novo mutations in a linearly growing mycelium. We show that S. commune accumulates mutations at a uniform rate of 1.4{middle dot}10-7 substitutions per nucleotide per meter of growth, which is 3 orders of magnitude higher than the corresponding rates in the oak Quercus robur and the fungus Armillaria gallica. This figure is consistent with the estimate obtained before, and suggests the lack of a dedicated germline in this system. If so, even a low per cell division mutation rate can translate into a very high per generation mutation rate when the number of cell divisions between consecutive meioses is large.

evolutionary biology↗

bioRxiv2018

Recombination in a natural population of the bdelloid rotifer Adineta vaga

Sexual reproduction which involves alternation of meiosis and syngamy is the ancestral condition of extant eukaryotes. Transitions to asexual reproduction were numerous, but most of the resulting eukaryotic lineages are rather short-lived. Still, there are several exceptions to this rule including darwinulid ostracods1,2 and timema stick insects3. The most striking of them is bdelloid rotifers4-6, microscopic freshwater invertebrates which underwent an extensive adaptive radiation after apparently losing meiosis over 10 Mya. Indeed, both the lack of males in numerous bdelloid species and the lack of proper homology between chromosomes6 rule out ordinary sex. However, this does not exclude the possibility of some other mode of interindividual genetic exchange and recombination in their populations7. Recent analyses based on a few loci suggested genetic exchanges in this group8,9, although this has been controversial10. Here, we compare complete genomes of 11 individuals from the wild population of the bdelloid rotifer Adineta vaga, and show that its genetic structure, which involves Hardy-Weinberg proportions of genotypes within loci and lack of linkage disequilibrium between distant loci, is incompatible with strictly clonal reproduction. Instead, it can emerge only under ongoing recombination between different individuals within this species, possibly through transformation. Such a genetic structure makes the population immune to negative long-term consequences of the loss of conventional meiosis11, although this does not necessarily imply that interindividual genetic exchanges in A. vaga are directly maintained by natural selection.

evolutionary biology↗

bioRxiv2018

Genetics of adaptation of the ascomycetous fungus Podospora anserina to submerged cultivation

Podospora anserina is a model ascomycetous fungus which shows pronounced phenotypic senescence when grown on solid medium but possesses unlimited lifespan under submerged cultivation. In order to study the genetic aspects of adaptation of P. anserina to submerged cultivation, we initiated a long-term evolution experiment. In the course of the first four years of the experiment, 125 single-nucleotide substitutions and 23 short indels were fixed in eight independently evolving populations. Six proteins that affect fungal growth and development evolved in more than one population; in particular, the G-protein alpha subunit FadA evolved in seven out of eight experimental populations. Parallel evolution at the level of genes and pathways, an excess of nonsense and missense substitutions, and an elevated conservation of proteins and their sites where the changes occurred suggest that many of the observed allele replacements were adaptive and driven by positive selection.\n\nAuthor summaryLiving beings adapt to novel conditions that are far from their original environments in different ways. Studying mechanisms of adaptation is crucial for our understanding of evolution. The object of our interest is a multicellular fungus Podospora anserina. This fungus is known for its pronounced senescence and a definite lifespan, but it demonstrates an unlimited lifespan and no signs of senescence when grown under submerged conditions. Soon after transition to submerged cultivation, the rate of growth of P. anserina increases and its pigmentation changes. We wanted to find out whether there are any genetic changes that contribute to adaptation of P. anserina to these novel conditions and initiated a long-term evolutionary experiment on eight independent populations. Over the first four years of the experiment, 148 mutations were fixed in these populations. Many of these mutations lead to inactivation of the part of the developmental pathway in P. anserina, probably reallocating resources to vegetative proliferation in liquid medium. Our observations imply that strong positive selection drives changes in at least some of the affected protein-coding genes.\n\nData AvailabilityGenome sequence data have been deposited at DDBJ/ENA/GenBank under accessions QHKV00000000 (founder genotype A; version QHKV01000000) and QHKU00000000 (founder genotype B; version QHKU01000000), with the respective BioSample accessions SAMN09270751 and SAMN09270757, under BioProject PRJNA473312. Sequencing data have been deposited at the SRA with accession numbers SRR7233712-SRR7233727, under the same BioProject.\n\nFundingExperimental work and sequencing were supported by the Russian Foundation for Basic Research (grants no. 16-04-01845a and 18-04-01349a). Bioinformatic analysis was supported by the Russian Science Foundation (grant no. 16-14-10173). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

evolutionary biology↗

bioRxiv2018

Two linked loci under mutation-selection balance and Muller’s ratchet

We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Mullers ratchet is governed by natural selection, instead of random drift.

evolutionary biology↗

bioRxiv2018

The comparative and genetic methods for East European Unionidae taxonomy

Taxonomy of freshwater mussels from family Unionidae has been ambiguous for a long time. A number of methods used for their identification, including the so-called comparative method, are based on shell morphology. However, this morphology turned out to have a high level of within-species variation, and the shape of the shell of a specimen depends strongly on its environment and conditions of growth. For these reasons, the number of species recognized by the comparative method kept increasing. We applied both the comparative morphological method and methods of molecular genetics to address the taxonomy of Unionidae. We performed the comprehensive study of 70 specimens of Unionidae mussels collected from the River Ivitza, Volga basin. The specimens represented 14 comparative species, belonging to 4 comparative genera of Unionidae: Colletopterum, Pseudanodonta, Unio and Crassiana. Sequencing of the nuclear (ITS1) and mitochondrial (COI, 16S rDNA) genetic regions revealed 5 groups with high within-group genetic homogeneity separated from each other by long genetic distances. According to the comparison with the available sequences, these groups correspond to 3 Eastern European genera and 5 species: Anodonta anatina, Pseudanodonta complanata, Unio pictorum, Unio tumidus and Unio crassus. The results obtained indicate that the comparative method is inappropriate for the taxonomic analysis of East European Unionidae.

zoology↗

bioRxiv2018

Architecture of parallel adaptation to freshwater in multiple populations of threespine stickleback

Threespine sticklebacks adapted to freshwater environments all over the Northern Hemisphere. This adaptation involved parallel recruitment of freshwater alleles in clusters of closely linked sites, or divergence islands (DIs). However, it is unclear to what extent the DIs involved in adaptation and the alleles within them coincide between populations adapting to similar environments. Here, we examine 10 freshwater populations of similar ages from the White Sea basin, and study the repeatability of patterns of adaptation in them. Overall, the 65 detected DIs tend to reside in regions of low recombination, underlining the role of reduced recombination in their establishment. Moreover, the DIs are clustered in the genome to the extent that is not explainable by the recombination rate alone, consistent with the divergence hitchhiking model. 21 out of the 65 DIs are universal; i.e., the frequency of freshwater alleles in them is increased in all analyzed populations. Universal DIs tend to have longer core region shared between populations, and the divergence between the marine and the freshwater haplotypes in them is higher, implying that they are older, also consistently with divergence hitchhiking. Within most DIs, the same set of sites distinguished the marine and the freshwater haplotypes in all populations; however, in some of the DIs, the genetic architecture of the freshwater haplotype differed between populations, suggesting that they could have been established by soft selective sweeps.

evolutionary biology↗

bioRxiv2017

Prevalence of loss-of-function alleles does not correlate with lifetime fecundity and other life-history traits in metazoans

Natural selection is possible only because all species produce more offspring than what is needed to maintain the population. Still, the lifetime number of offspring varies widely across species. One can expect natural selection to be stronger in high-fecundity species. We analyzed the prevalence of loss-of-function alleles in 32 metazoan species and have found that, in contrast to this expectation, the strength of negative selection does not correlate with lifetime fecundity, as well as with other life-history traits. Perhaps, higher random mortality in high-fecundity species negates the effect of increased opportunity for selection.

evolutionary biology↗

bioRxiv2017

Bursts of amino acid replacements in protein evolution

Evolution can occur both gradually and through alternating episodes of stasis and rapid changes. However, the prevalence and magnitude of fluctuations of the rate of evolution remains obscure. Detecting a rapid burst of changes requires a detailed record of past evolution, so that events that occurred within a short time interval can be identified. Here, we use the phylogenies of the Baikal Lake amphipods and of Catarrhini, which contain very short internal edges facilitating this task. We detect 6 radical bursts of evolution of individual proteins during such short time periods, each involving between 6 and 38 amino acid substitutions. These bursts were extremely unlikely to have occurred neutrally, and were apparently caused by positive selection. On average, in the course of a time interval required for one synonymous substitution per site, a protein undergoes a strong burst of rapid evolution with probability at least ~0.01.

evolutionary biology↗