The genomic features that affect the lengths of 5’ untranslated regions in multicellular eukaryotes

<p>Abstract</p> <p>Background</p> <p>The lengths of 5’UTRs of multicellular eukaryotes have been suggested to be subject to stochastic changes, with upstream start codons (uAUGs) as the major constraint to suppress 5’UTR elongation. However, this stochastic model cannot fully explain the variations in 5’UTR length. We hypothesize that the selection pressure on a combination of genomic features is also important for 5’UTR evolution. The ignorance of these features may have limited the explanatory power of the stochastic model. Furthermore, different selective constraints between vertebrates and invertebrates may lead to differences in the determinants of 5’UTR length, which have not been systematically analyzed.</p> <p>Methods</p> <p>Here we use a multiple linear regression model to delineate the correlation between 5’UTR length and the combination of a series of genomic features (G+C content, observed-to-expected (OE) ratios of uAUGs, upstream stop codons (uSTOPs), methylation-related CG/UG dinucleotides, and mRNA-destabilizing UU/UA dinucleotides) in six vertebrates (human, mouse, rat, chicken, African clawed frog, and zebrafish) and four invertebrates (fruit fly, mosquito, sea squirt, and nematode). The relative contributions of each feature to the variation of 5’UTR length were also evaluated.</p> <p>Results</p> <p>We found that 14%~33% of the 5’UTR length variations can be explained by a linear combination of the analyzed genomic features. The most important genomic features are the OE ratios of uSTOPs and G+C content. The surprisingly large weightings of uSTOPs highlight the importance of selection on upstream open reading frames (which include both uAUGs and uSTOPs), rather than on uAUGs <it>per se</it>. Furthermore, G+C content is the most important determinants for most invertebrates, but for vertebrates its effect is second to uSTOPs. We also found that shorter 5’UTRs are affected more by the stochastic process, whereas longer 5’UTRs are affected more by selection pressure on genomic features.</p> <p>Conclusions</p> <p>Our results suggest that upstream open reading frames may be the real target of selection, rather than uAUGs. We also show that the selective constraints on genomic features of 5’UTRs differ between vertebrates and invertebrates, and between longer and shorter 5’UTRs. A more comprehensive model that takes these findings into consideration is needed to better explain 5’UTR length evolution.</p

Asymmetric Strand Segregation: Epigenetic Costs of Genetic Fidelity?

Asymmetric strand segregation has been proposed as a mechanism to minimize effective mutation rates in epithelial tissues. Under asymmetric strand segregation, the double-stranded molecule that contains the oldest DNA strand is preferentially targeted to the somatic stem cell after each round of DNA replication. This oldest DNA strand is expected to have fewer errors than younger strands because some of the errors that arise on daughter strands during their synthesis fail to be repaired. Empirical findings suggest the possibility of asymmetric strand segregation in a subset of mammalian cell lineages, indicating that it may indeed function to increase genetic fidelity. However, the implications of asymmetric strand segregation for the fidelity of epigenetic information remain unexplored. Here, I explore the impact of strand-segregation dynamics on epigenetic fidelity using a mathematical-modelling approach that draws on the known molecular mechanisms of DNA methylation and existing rate estimates from empirical methylation data. I find that, for a wide range of starting methylation densities, asymmetric—but not symmetric—strand segregation leads to systematic increases in methylation levels if parent strands are subject to de novo methylation events. I found that epigenetic fidelity can be compromised when enhanced genetic fidelity is achieved through asymmetric strand segregation. Strand segregation dynamics could thus explain the increased DNA methylation densities that are observed in structured cellular populations during aging and in disease

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

Parent-of-origin effects (POE) are observed when there are different effects from alleles inherited from the two parents on phenotypic measures. Here, Zeng et al. study POE on DNA methylation in 5,101 individuals and identify genetic variants that associate with methylation variation via POE and their potential phenotypic consequences

Methamphetamine Causes Differential Alterations in Gene Expression and Patterns of Histone Acetylation/Hypoacetylation in the Rat Nucleus Accumbens

Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further

Disappearance of back-to-back high-p(T) hadron correlations in central Au+Au collisions at root s(NN)=200 GeV

Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudorapidity range and full azimuth in Au+Au and p+p collisions at roots(NN)=200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes previously observed in high-energy collisions. A strong back-to-back correlation exists for p+p and peripheral Au+Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium