Calcitonin: characterisation and expression in a teleost fish, Fugu rubripes

The present report describes the structure and expression of the calcitonin gene in Fugu rubripes. It is composed of 4 exons and 3 introns. Splicing of exons 1, 2 and 3 generates the calcitonin pre-proprotein, while splicing of exons 1, 2 and 4 generates calcitonin gene-related protein (CGRP). Exons 1 and 2 encoding the signal sequence and the N-terminal peptide are common in both the gene products and this gene organisation has been conserved in human, rat, chicken and salmon. The gene environment around calcitonin in Fugu has been poorly conserved when compared with human, apart from a small gene cluster. The calcitonin gene in Fugu has a widespread tissue distribution but it is most highly expressed in the brain. The abundance of gene expression in the ultimobranchial gland and the pituitary indicates that these are important sites of production and that the peptide is probably secreted into the circulation and/or acts as a paracrine or autocrine controlling factor. Whilst the function of calcitonin in fish is still largely unknown, the distribution described here suggests that one of the potential functions may be as a neuropeptide.info:eu-repo/semantics/publishedVersio

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Upper limits on neutrino masses from the 2dFGRS and WMAP: the role of priors

Solar, atmospheric, and reactor neutrino experiments have confirmed neutrino oscillations, implying that neutrinos have non-zero mass, but without pinning down their absolute masses. While it is established that the effect of neutrinos on the evolution of cosmic structure is small, the upper limits derived from large-scale structure data could help significantly to constrain the absolute scale of the neutrino masses. In a recent paper the 2dF Galaxy Redshift Survey (2dFGRS) team provided an upper limit m_nu,tot < 2.2 eV, i.e. approximately 0.7 eV for each of the three neutrino flavours, or phrased in terms of their contributioin to the matter density, Omega_nu/Omega_m < 0.16. Here we discuss this analysis in greater detail, considering issues of assumed 'priors' like the matter density Omega_m and the bias of the galaxy distribution with respect the dark matter distribution. As the suppression of the power spectrum depends on the ratio Omega_nu/Omega_m, we find that the out-of- fashion Mixed Dark Matter Model, with Omega_nu=0.2, Omega_m=1 and no cosmological constant, fits the 2dFGRS power spectrum and the CMB data reasonably well, but only for a Hubble constant H_0<50 km/s/Mpc. As a consequence, excluding low values of the Hubble constant, e.g. with the HST Key Project is important in order to get a strong constraint on the neutrino masses. We also comment on the improved limit by the WMAP team, and point out that the main neutrino signature comes from the 2dFGRS and the Lyman alpha forest.Comment: 24 pages, 12 figures Minor changes to matched version published in JCA