arXiv subjects

Dmitri Parkhomchuk

Publications and source records attributed to Dmitri Parkhomchuk.

4 recordsLinked to original sources

arXiv2016

Genetic recombination as DNA repair

Maintenance of sexual reproduction and genetic recombination imposes physiological costs when compared to parthenogenic reproduction, most prominently: for maintaining the corresponding (molecular) machinery, for finding a mating partner, and through the decreased fraction of females in a population, which decreases the reproductive capacity. Based on principles from information theory, we have previously developed a new population genetic model, and applying it in simulations, we have recently hypothesized that all species maintain the maximum genomic complexity that is required by their niche and allowed by their mutation rate and selection intensity. Applying this idea to the complexity overhead of recombination maintenance, its costs must be more than compensated by an additional capacity for complexity in recombining populations. Here, we show a simple mechanism, where recombination helps to maintain larger biases of alleles frequencies in a population, so the advantageous alleles can have increased frequency. This allows recombining populations to maintain higher fitness and phenotypic efficiency in comparison with asexual populations with the same parameters. Random mating alone already significantly increases the ability to maintain genomic and phenotypic complexity. Sexual selection provides additional capacity for this complexity. The model can be considered as a unifying synthesis of previous hypotheses about the roles of recombination in Muller's ratchet, mutation purging and Red Queen dynamics, because the introduction of recombination both increases population frequencies of beneficial alleles and decreases detrimental ones. In addition, we suggest simple explanations for niche-dependent prevalence of transient asexuality and the exceptional asexual lineage of Bdelloid rotifers.

q-bio.PE↗

arXiv2006

Di-nucleotide Entropy as a Measure of Genomic Sequence Functionality

Considering vast amounts of genomic sequences of mostly unknown functionality, in-silico prediction of functional regions is an important enterprise. Many genomic browsers employ GC content, which was observed to be elevated in gene-rich functional regions. This report shows that the entropy of di- and tri-nucleotides distributions provides a superior measure of genomic sequence functionality, and proposes an explanation on why the GC content must be elevated (closer to 50%) in functional regions. Regions with high entropy strongly co-localize with exons and provide genome-wide evidences of purifying selection acting on non-coding regions, such as decreased SNPs density. The observations suggest that functional non-coding regions are optimised for mutation load in a way, that transition mutations have less impact on functionality than transversions, leading to the decrease in transversions to transitions ratio in functional regions.

q-bio.GN↗

arXiv2006

Genetic Variability of Splicing Sites

Splicing sites provide unique statistics in human genome due to their large number and reasonably complete annotation. Analyses of the cumulative SNPs distribution in splicing sites reveal a few interesting observations. While a degree of the nucleotide conservation reflects on the SNPs density monotonically, no detectable changes in the SNPs frequencies spectrum were found. Semi-conserved nucleotide sites harbor transition mutations predominantly. We propose that such transition preference is caused by co-evolution of a site with corresponding binding agents. Since transitions in humans and similarly in other organisms are almost twice as frequent as transversions, this adaptation significantly lowers the mutation load.

q-bio.GN↗

arXiv2004

Two Major Paths of Gene-Duplicates Evolution

Evolving genomes increase a number of their genes by gene duplications. To escape degradation in a functionless pseudogene, any gene duplicate needs to be guarded by negative (purifying) selection from otherwise inevitable fixation of degenerative mutations. In the present study we focus on the evolutionary stage at which new duplicates come under such surveillance. Our analyses of several genomes indicate that in about 10% gene pairs, selection begins to guard a new gene copy very soon after a duplication event whereas the vast majority (90%) of extra genes remain redundant and unrecognised by selection. Such duplicates accumulate all mutations (including degenerative) in neutral fashion and are actually destined to become pseudogenes. We revealed this "two-stream" evolutionary pattern by the analysis of mutations in 2nd versus 3rd codon positions but not by the routinely used ratio of amino acid replacements (R) versus silent substitutions (S), i.e. the '2nd vs. 3rd' metric proved to be more resolving than the traditional 'R vs. S' one for distinguishing neutrally evolving future pseudogenes from their functional counterparts controlled by negative selection. In gene databases for large genomes, hundreds of future pseudogenes are annotated as functional genes because they do look like intact and valuable by standard criteria, including even active transcription and translation. Apparently, these "pseudogenes-to-be" over-cloud and mimic those very infrequent gene duplicates with increased sequence evolution rates driven by positive selection.

q-bio.PE↗