Abstract: Имеются данные высокопроизводительного секвенирования 8-ми геномов особей Ciona Savignyi и референсный геном данного вида. Путем картирования имеющихся чтений на референсный геном предполагается улучшить его качество, а также получить новые данные об однонуклеотидном полиморфизме, вставках и делециях, и структурных вариациях, которые будут использованы в анализе эволюции этого вида.

Abstract: Mutation rate varies between adjacent sites. A part of this variation isdue to well-recognized contexts, but another part is cryptic. However, the overall mutation rateprovides just the most basic description of the mutation process. We investigatedvariation in the most fundamental parameter characterizing thepattern ofmutation, the transversion/transition ratio, and detected a lot of cryptic variation.Incontrast to rate, pattern varies not only at individual sites.

Abstract: Both the mutation rate and the selective pressure are non-uniform along the non-coding DNA segments. However, the durability of this variation is poorly understood. Here, we study the tendency of pairs of neighboring substitutions in the non-coding sequence to occur in the same phylogenetic lineage. The lineage in which each substitution has occurred is revealed by maximum parsimony in comparison of human with chimp (using orangutan as an outgroup), and in comparison of D. melanogaster and D. simulans (using D. erecta as an outgroup). In both cases, the substitutions in neighboring nucleotides tend to occur in the same lineage. This effect decreases with distance between nucleotides, but is still pronounced for substitutions at ~10 nucleotides from each other. Possible mutational and selective explanations for this pattern are discussed.

Abstract: In our work we studied mode of selection acting on intron length, which can be stabilizing (preferring the optimal intron length) or directional (with no optimum on fitness landscape) in it's nature. The intron length can be affected by an insertion or a deletion event (collectively, an indel). Low-frequency alleles in population reveal action of mutational process, whereas at higher frequencies proportion of slightly deleterious alleles declines compared to neutral variants. Such decline represents the action of the negative seletion. In our work we show that mutation process smooths the peak of the intron length distribution to both sides. But selection, preferring insertions to deletions, shifts distribution to the right, with introns of length more than 60bp having tendency to lengthen independent on their current length, which implies directional selection on intron length.

Abstract: Сплайсинг - это процесс вырезания из первичного транскрипта участков (интронов) и сшивания оставшихся участков (экзонов). Границы экзонов и интронов маркированы специальными последовательностями - сайтами сплайсинга (СС). Мутации в СС ограничены действием отбора, поэтому сайты сплайсинга являются высококонсервативными последовательностями в геномах эукариот. Т.к. размер выборки сайтов сплайсинга достаточно велик (несколько тысяч), они являются удобным модельным объектом для изучения эволюции последовательностей, находящихся под действием отбора. В данной работе произведен анализ эволюции СС в геномах рода Drosophila. Для каждой позиции сайта мы восстанавливали матрицу замен и изучали её свойства. Для каждой позиции СС мы стремились понять происходит ли приближение к консенсусу или отдаление от него, а также сравнить частоты замен в позициях, находящихся под действием отбора с нейтральным контролем. В большей степени нас интересовали переходы из консенсусных (т.е. самых частых в данной позиции) нуклеотидов в неконсенсусные и обратно. Отдельно фиксировались случаи отрицательно и положительного отбора.

Abstract: Fitness landscape, the function which relates fitness to genotype, can be visualized as isolated peaks separated by valleys. One of the interesting questions in evolutionary biology is whether it is possible for evolving organisms to overpass valleys of low fitness variants to achieve high fitness. We studied this possibility for double substitutions in protein coding sequences. We used the polymorphism of 162 lines of D.melanogaster to analyze the polymorphic codons separated by two nucleotide substitutions. When these two codons encoded the same amino acid (serine), the intermediate variant was observed more rarely than it was expected, implying selection against the intermediate variant. For other pairs of nonsynonymous substitutions, we could assess how the frequency of the intermediate variant depended on the absolute differences in amino acid properties between the three variants. The intermediate variant in two-substitution codons tends to be deleterious, and functional genome regions are depleted of it. Although the two substitutions typically represent two independent mutation events, they follow each other very quickly.

Abstract: Despite decades of debate, our understanding of dominance effects remains elusive. Since the seminal works of Fisher and Wright, it has been assumed that large-effect mutations tend to be recessive, while the effects of small-effect mutations is usually additive. Nonsense mutations prevent the synthesis of the gene product, and can be safely assumed to be large-effect; nevertheless, they can reach a substantial frequency in the population. Here, we use 162 complete genome sequences of D. melanogaster to study the frequency of nonsense mutations segregating in the population. In 10.2% of genes in our D. melanogaster sample, stop codons segregate at non-trivial frequencies. Since the alleles carrying stop codons on the X chromosome are hemizygous and more visible to selection, we expected the nonsense mutations to have lower frequencies on the X chromosome. Surprisingly, the fraction of genes carrying a nonsense mutation was virtually identical between the X chromosome (10.0%) and autosomes (10.2%). The allele frequency spectra, which can reveal the action of weak selection, were also similar. The significance of these results for our understanding of dominance is discussed.