Biology subjects

Bazykin, G. A.

Publications and source records attributed to Bazykin, G. A..

7 recordsLinked to original sources

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↗

bioRxiv2018

The Evolutionary Moulding in plant-microbial symbiosis: matching population diversity of rhizobial nodA and legume NFR5 genes

We propose the Evolutionary Moulding hypothesis that population diversities of partners in nitrogen-fixing rhizobium-legume symbiosis are matched, and tested it in nucleotide polymorphism of symbiotic genes encoding two components of the plant-bacteria signalling system. The first component is the rhizobial nodA acyltransferase involved in the fatty acid tail decoration of Nod factor (rhizobia signalling molecule). The second component is the plant NFR5 receptor, putatively required for Nod-factor binding.\n\nWe collected three wild growing legume species together with soil samples adjacent to the roots (soil pool) from one large 25-year fallow: Vicia sativa, Lathyrus pratensis and Trifolium hybridum nodulated by one of the two Rhizobium leguminosarum biovars (viciae and trifolii). For each plant species we prepared three pools for DNA extraction: the plant pool (30 plant indiv.), the nodule pool (90 nodules) and the soil pool (30 samples). NFR5 gene libraries from the plant pool and nodA gene libraries from nodule and soil pools were sequenced by Sanger technology and High-throughput pyrosequencing, respectively. Analysis of the data demonstrated concordance in population diversities of one symbiotic partner (rhizobia) the second partner (legume host), in line with the Evolutionary Moulding hypothesis. This effect was evinced by the following observations for each plant species: (1) significantly increased diversity in the nodule nodA popset (set of gene sequences derived from the nodule population) compared to the soil popset; (2) a monotonic relationship between the diversity in the plant NFR5 gene popset and the nodule rhizobial nodA gene popset; and (3) higher topological similarity of the NFR5 gene tree with the nodA gene tree of the nodule popset, than with the nodA gene tree of the soil popset. Both nonsynonymous diversity and Tajimas D were increased in the nodule popsets compared to the soil popsets, consistent with relaxation of negative selection and/or admixture of balancing selection underlying the Evolutionary Moulding effect. We propose that the observed genetic concordance arises from the selection of particular characteristics of the nodule nodA genes by the host plant.

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↗

bioRxiv2017

Error-prone bypass of DNA lesions during lagging strand replication is a common source of germline and cancer mutations

Spontaneously occurring mutations are of great relevance in diverse fields including biochemistry, oncology, evolutionary biology, and human genetics. Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity as well as many forms of DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutations remain completely unknown. Here, based on the mutational asymmetry with respect to the direction of replication and transcription, we suggest that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Asymmetry with respect to transcription is believed to be mediated by the action of transcription-coupled DNA repair (TC-NER). TC-NER selectively repairs DNA lesions on the transcribed strand; as a result, lesions on the non-transcribed strand are preferentially converted into mutations. In human polymorphism we detect a striking similarity between transcriptional asymmetry and asymmetry with respect to replication fork direction. This parallels the observation that damage-induced mutations in human cancers accumulate asymmetrically with respect to the direction of replication, suggesting that DNA lesions are asymmetrically resolved during replication. Re-analysis of XR-seq data, Damage-seq data and cancers with defective NER corroborate the preferential error-prone bypass of DNA lesions on the lagging strand. We experimentally demonstrate that replication delay greatly attenuates the mutagenic effect of UV-irradiation, in line with the key role of replication in conversion of DNA damage to mutations. We conservatively estimate that at least 10% of human germline mutations arise due to DNA damage rather than replication infidelity. The number of these damage-induced mutations is expected to scale with the number of replications and, consequently, paternal age.

biochemistry↗

bioRxiv2017

POLD replicates both strands of small kilobase-long replication bubbles initiated at a majority of human replication origins

Error-prone mutants of polymerase epsilon (POLE*) or polymerase delta (POLD1*) induce a mutator phenotype in human cancers. Here we show that the rate of mutations introduced by POLD1* is elevated by 50%, while the rate of POLE*-induced mutations is decreased twofold, within one kilobase from replication origins. These results support a model in which POLD1 replicates both the leading and the lagging strands within a kilobase from an origin. The magnitude of the mutational bias suggests that the probability of an individual origin to initiate replication exceeds 50%, which is much higher than previous estimates. Using additional data from nascent DNA sequencing and Okazaki fragments sequencing (OK-seq) experiments, we showed that a majority of origins are firing at each replication round, but the initiated replication fork does not propagate further than 1Kb in both directions. Analyses based on mutational data and on OK-seq data concordantly suggest that only approximately a quarter of fired origins result in a processive replication fork. Taken together, our results provide a new model of replication initiation.

molecular biology↗

bioRxiv2017

Pathogenic Amino Acid Variants In Mitochondrial Proteins More Frequently Arise In Lineages Closely Related To Human Than In Distantly Related Lineages

Propensities for different amino acids within a protein site change in the course of evolution, so that an amino acid deleterious in a particular species may be acceptable at the same site in a different species. Here, we study the amino acid-changing variants in human mitochondrial genes, and analyze their occurrence in non-human species. We show that substitutions giving rise to the human amino acid variant tend to occur in lineages closely related to human more frequently than in more distantly related lineages, indicating that a human variant is more likely to be deleterious in more distant species. Unexpectedly, amino acids corresponding to pathogenic alleles in humans also more frequently originate at more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable in human mitochondria than a variant that may only be fit after a substantial perturbation of the protein structure.\n\nSignificanceHomologous proteins can carry different amino acids at the same position in different species. These changes can be neutral, or can reflect differences in the pressure of selection on these sites. We hypothesized that amino acids observable in human population appear on average more frequently in close than in distant human relatives. For mitochondrial proteins, we observe this for both frequent and rare human alleles. Unexpectedly, substitutions that would be pathogenic in humans also more frequently appear in species more closely related to humans than in distantly related ones. Therefore, despite their pathogenicity, these variants are on average more acceptable in humans than other amino acids that were observed at this site in distantly related species.

evolutionary biology↗