29 research outputs found

    Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection

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    Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be preserved by negative selection at important sites but destroyed by mutation at sites under no selection. Thus, there may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness. We studied the impact of CpG context on the rate of human–chimpanzee divergence and on intrahuman nucleotide diversity at non-synonymous coding sites. We compared nucleotides that occupy identical positions within codons of identical amino acids and only differ by being within versus outside CpG context. Nucleotides within CpG context are under a stronger negative selection, as revealed by their lower, proportionally to the mutation rate, rate of evolution and nucleotide diversity. In particular, the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a CpG site. Thus, sites with different mutation rates are not necessarily selectively equivalent. This suggests that the mutation rate may complement sequence conservation as a characteristic predictive of functional importance of nucleotide sites

    How life changes itself: The Read–Write (RW) genome

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    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Biochemical changes in Oenothera biennis plants infected by 'Candidatus Phytoplasma solani'

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    The aim of the present paper was to study the response of Oenothera biennis L. to 'Candidatus Phytoplasma solani' (Stolbur) infection by analyzing total sugars, polyphenols, photosynthetic pigments content and the antioxidant capacity in leaves and roots of healthy and infected plants. The infection caused a significant increase in peroxidation of lipids, phenylalanine ammonia-lyase activity, total sugar, polyphenols and anthocyanins content (2.8, 2.6, 1.8, 1.4, 6.8 fold, respectively), as well as a decrease in photosynthetic pigments (2-6 fold) and total flavonoids (1.5 fold) in the leaves of Oe. biennis. Changes in these parameters were insignificant in the roots except for the total polyphenols content that was 2.7 times higher in the infected ones. Reduced gluthatione content in both tested organs was not affected by the infection (3.7 and 1.7 mu mol/g fresh weight of leaves and roots, respectively). The elevated content of total sugars, flavonoids and polyphenols, as well as the reduction of photosynthetic pigments and anthocyanins in infected plants are indicative of changes in the metabolism of Oe. biennis affected by the Stolbur phytoplasma. In addition to reduction of chlorophyll and carotenoids, the phytoplasma accelerated leaf senescence. Plants responded to the infection via enhanced superoxide anion scavenging, even though this reaction did not prevent, apparently, membrane damage in analysed leaves. This investigation presents new data on the effect of a phytoplasma infection on its host
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