Nucleotide repeats in mitochondrial genome determine human lifespan

Direct nucleotide repeats can facilitate deletions of segments of mitochondrial genome1, leading to a wide range of neuromuscular disorders1,2 as well as aging2,3 in humans. We hypothesized that the number of the direct perfect repeats in human mitochondrial genomes influences longevity through the formation of harmful mtDNA deletions in the somatic cells. The analysis of the complete mitochondrial genomes of 762 unrelated Japanese individuals4-6 reveals a negative correlation between the abundance of the direct perfect repeats and the expected longevity. This association is largely due to the disruption of the common repeat (8470,13447) by a point mutation 8473C which occurred at the origin of the D4a haplogroup characterized by extreme longevity in Japan7. Our results provide the first evidence for correlation between the number of nucleotide repeats and the lifespan on intraspecific level

Rate of promoter class turn-over in yeast evolution

BACKGROUND: Phylogenetic conservation at the DNA level is routinely used as evidence of molecular function, under the assumption that locations and sequences of functional DNA segments remain invariant in evolution. In particular, short DNA segments participating in initiation and regulation of transcription are often conserved between related species. However, transcription of a gene can evolve, and this evolution may involve changes of even such conservative DNA segments. Genes of yeast Saccharomyces have promoters of two classes, class 1 (TATA-containing) and class 2 (non-TATA-containing). RESULTS: Comparison of upstream non-coding regions of orthologous genes from the five species of Saccharomyces sensu stricto group shows that among 212 genes which very likely have class 1 promoters in S. cerevisiae, 17 probably have class 2 promoters in one or more other species. Conversely, among 322 genes which very likely have class 2 promoters in S. cerevisiae, 44 probably have class 1 promoters in one or more other species. Also, for at least 2 genes from the set of 212 S. cerevisiae genes with class 1 promoters, the locations of the TATA consensus sequences are substantially different between the species. CONCLUSION: Our results indicate that, in the course of yeast evolution, a promoter switches its class with the probability at least ~0.1 per time required for the accumulation of one nucleotide substitution at a non-coding site. Thus, key sequences involved in initiation of transcription evolve with substantial rates in yeast

Инновационный подход к управлению педагогическим коллективом в детском саду

Table S5. Mean proportions of LoF alleles among all, core and hard-core genes for each species. (XLSX 12 kb

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

Abstract Background Natural selection is possible only because all species produce more offsprings than what is needed to maintain the population. Still, the lifetime number of offspring varies widely across species. One may expect natural selection to be stronger in high-fecundity species. Alternatively, natural selection could be stronger in species where a female invests more into an individual offspring. This issue needed to be addressed empirically. Results We analyzed the prevalence of loss-of-function alleles in 35 metazoan species and have found that the strength of negative selection does not correlate with lifetime fecundity or other life-history traits. Conclusions Higher random mortality in high-fecundity species may negate the effect of increased opportunity for selection. Perhaps, invariance of the strength of negative selection across a wide variety of species emerges because natural selection optimized the life history in each of them, leading to the strongest possible competition. Reviewers This article was reviewed by Nicolas Galtier and I. King Jordan.https://deepblue.lib.umich.edu/bitstream/2027.42/142408/1/13062_2018_Article_206.pd

Extensive parallelism in protein evolution

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The limits of normal approximation for adult height

Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait

Detecting Past Positive Selection through Ongoing Negative Selection

Detecting positive selection is a challenging task. We propose a method for detecting past positive selection through ongoing negative selection, based on comparison of the parameters of intraspecies polymorphism at functionally important and selectively neutral sites where a nucleotide substitution of the same kind occurred recently. Reduced occurrence of recently replaced ancestral alleles at functionally important sites indicates that negative selection currently acts against these alleles and, therefore, that their replacements were driven by positive selection. Application of this method to the Drosophila melanogaster lineage shows that the fraction of adaptive amino acid replacements remained approximately 0.5 for a long time. In the Homo sapiens lineage, however, this fraction drops from approximately 0.5 before the Ponginae–Homininae divergence to approximately 0 after it. The proposed method is based on essentially the same data as the McDonald–Kreitman test but is free from some of its limitations, which may open new opportunities, especially when many genotypes within a species are known

Transcriptome‐based phylogeny of endemic Lake Baikal amphipod species flock: fast speciation accompanied by frequent episodes of positive selection

Endemic species flocks inhabiting ancient lakes, oceanic islands and other long‐lived isolated habitats are often interpreted as adaptive radiations. Yet molecular evidence for directional selection during species flocks radiation is scarce. Using partial transcriptomes of 64 species of Lake Baikal (Siberia, Russia) endemic amphipods and two nonendemic outgroups, we report a revised phylogeny of this species flock and analyse evidence for positive selection within the endemic lineages. We confirm two independent invasions of amphipods into Baikal and demonstrate that several morphological features of Baikal amphipods, such as body armour and reduction in appendages and sensory organs, evolved in several lineages in parallel. Radiation of Baikal amphipods has been characterized by short phylogenetic branches and frequent episodes of positive selection which tended to be more frequent in the early phase of the second invasion of amphipods into Baikal when the most intensive diversification occurred. Notably, signatures of positive selection are frequent in genes encoding mitochondrial membrane proteins with electron transfer chain and ATP synthesis functionality. In particular, subunits of both the membrane and substrate‐level ATP synthases show evidence of positive selection in the plankton species Macrohectopus branickii, possibly indicating adaptation to active plankton lifestyle and to survival under conditions of low temperature and high hydrostatic pressures known to affect membranes functioning. Other functional categories represented among genes likely to be under positive selection include Ca‐binding muscle‐related proteins, possibly indicating adaptation to Ca‐deficient low mineralization Baikal waters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136009/1/mec13927.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136009/2/mec13927_am.pd

Prevalence of Epistasis in the Evolution of Influenza A Surface Proteins

The surface proteins of human influenza A viruses experience positive selection to escape both human immunity and, more recently, antiviral drug treatments. In bacteria and viruses, immune-escape and drug-resistant phenotypes often appear through a combination of several mutations that have epistatic effects on pathogen fitness. However, the extent and structure of epistasis in influenza viral proteins have not been systematically investigated. Here, we develop a novel statistical method to detect positive epistasis between pairs of sites in a protein, based on the observed temporal patterns of sequence evolution. The method rests on the simple idea that a substitution at one site should rapidly follow a substitution at another site if the sites are positively epistatic. We apply this method to the surface proteins hemagglutinin and neuraminidase of influenza A virus subtypes H3N2 and H1N1. Compared to a non-epistatic null distribution, we detect substantial amounts of epistasis and determine the identities of putatively epistatic pairs of sites. In particular, using sequence data alone, our method identifies epistatic interactions between specific sites in neuraminidase that have recently been demonstrated, in vitro, to confer resistance to the drug oseltamivir; these epistatic interactions are responsible for widespread drug resistance among H1N1 viruses circulating today. This experimental validation demonstrates the predictive power of our method to identify epistatic sites of importance for viral adaptation and public health. We conclude that epistasis plays a large role in shaping the molecular evolution of influenza viruses. In particular, sites with , which would normally not be identified as positively selected, can facilitate viral adaptation through epistatic interactions with their partner sites. The knowledge of specific interactions among sites in influenza proteins may help us to predict the course of antigenic evolution and, consequently, to select more appropriate vaccines and drugs