Birth-and-death evolution with strong purifying selection in the histone H1 multigene family and the origin of "orphon" H1 genes

[Abstract:] Histones are small basic nuclear proteins with critical structural and functional roles in eukaryotic genomes. The H1 multigene family constitutes a very interesting histone class gathering the greatest number of isoforms, with many different arrangements in the genome, including clustered and solitary genes, and showing replication-dependent (RD) or replication-independent (RI) expression patterns. The evolution of H1 histones has been classically explained by concerted evolution through a rapid process of interlocus recombination or gene conversion. Given such intriguing features, we have analyzed the long-term evolutionary pattern of the H1 multigene family through the evaluation of the relative importance of gene conversion, point mutation, and selection in generating and maintaining the different H1 subtypes. We have found the presence of an extensive silent nucleotide divergence, both within and between species, which is always significantly greater than the nonsilent variation, indicating that purifying selection is the major factor maintaining H1 protein homogeneity. The results obtained from phylogenetic analysis reveal that different H1 subtypes are no more closely related within than between species, as they cluster by type in the topologies, and that both RD and RI H1 variants follow the same evolutionary pattern. These findings suggest that H1 histones have not been subject to any significant effect of interlocus recombination or concerted evolution. However, the diversification of the H1 isoforms seems to be enhanced primarily by mutation and selection, where genes are subject to birth-and-death evolution with strong purifying selection at the protein level. This model is able to explain not only the generation and diversification of RD H1 isoforms but also the origin and long-term persistence of orphon RI H1 subtypes in the genome, something that is still unclear, assuming concerted evolution.Xunta de Galicia; PGIDT (10PX110304

Molecular and evolutionary analysis of mussel histone genes ("Mytilus" spp.): possible evidence of an "orphon origin" for H1 histone genes

[Abstract:] Linker histones are a divergent group of histone proteins with an independent evolutionary history in which, besides somatic subtypes, tissue- and differentiation-specific subtypes are included. In the present work H1 histone coding and noncoding segments from five Mytilus mussel species (Mollusca: Bivalvia) widely distributed throughout the world have been determined and characterized. Analysis of promoter regions shows clear homologies among Mytilus H1 genes, sea urchin H1 genes, and vertebrate differentiation-specific H1 subtypes (H5 and H10), all having an H4 box motif in common. The amino acid sequence of the H1 protein central conserved domain is also closely related to that previously defined for the vertebrate divergent subtypes. A phylogenetic tree reconstructed from different H1 genes from several species strengthens the hypothesis of an “orphon” origin for the Mytilus H1 genes, as well as for the H10/H5 genes from vertebrates and the H1D gene from the sea urchin Strongylocentrotus purpuratus, is suggested. As additional data, the average copy number of the H1 genes in the species analyzed was estimated as being 100 to 110 copies per haploid genome, where FISH revealed telomeric chromosomal location for several H1 copies in M. galloprovincialis. The contribution of such proximity to heterochromatic regions over the amount of codon bias detected for H1 genes is discussed.Ministerio de Ciencia e Innovación; IFD97-129

Molecular evolutionary characterization of the mussel "Mytilus" histone multigene family: first record of a tandemly repeated unit of five histone genes containing an H1 subtype with orphon features

[Abstract] The present work represents the first characterization of a clustered histone repetitive unit containing an H1 gene in a bivalve mollusk. To complete the knowledge on the evolutionary history of the histone multigene family in invertebrates, we undertake its characterization in five mussel Mytilus species, as an extension of our previous work on the H1 gene family. We report the quintet H4–H2B–H2A–H3–H1 as the major organization unit in the genome of Mytilus galloprovincialis with two 5S rRNA genes with interspersed nontranscribed spacer segments linked to the unit, which is not justified by their cotranscription with histone genes. Surprisingly, 3′ UTR regions of histone genes show two different mRNA termination signals, a stem-loop and a polyadenylation signal, both related to the evolution of histone gene expression patterns throughout the cell cycle. The clustered H1 histones characterized share essential features with “orphon” H1 genes, suggesting a common evolutionary origin for both histone subtypes which is supported by the reconstructed phylogeny for H1 genes. The characterization of histone genes in four additional Mytilus species revealed the presence of strong purifying selection acting among the members of the family. The chromosomal location of most of the core histone genes studied was identified by FISH close to telomeric regions in M. galloprovincialis. Further analysis on nucleotide variation would be necessary to assess if H1 proteins evolve according to the birth-and-death model of evolution and if the effect of the strong purifying selection maintaining protein homogeneity could account for the homologies detected between clustered and “orphon” variants.Xunta de Galicia; 10PX110304P

Common evolutionary origin and birth-and-death process in the replication-independent histone H1 isoforms from vertebrate and invertebrate genomes

[Abstract]The H1 histone multigene family shows the greatest diversity of isoforms among the five histone gene families, including replication-dependent (RD) and replication-independent (RI) genes, according to their expression patterns along the cell cycle and their genomic organization. Although the molecular characterization of the RI isoforms has been well documented in vertebrates, similar information is lacking in invertebrates. In this work we provide evidence for a polyadenylation signature in the Mytilus “orphon” H1 genes similar to the polyadenylation characteristic of RI H1 genes. These mussel genes, together with the sea urchin H1δ genes, are part of a lineage of invertebrate “orphon” H1 genes that share several control elements with vertebrate RI H1 genes. These control elements include the UCE element, H1-box and H4-box. We provide evidence for a functional evolution of vertebrate and invertebrate RI H1 genes, which exhibit a clustering pattern by type instead of by species, with a marked difference from the somatic variants. In addition, these genes display an extensive silent divergence at the nucleotide level which is always significantly larger than the nonsilent. It thus appears that RI and RD H1 isoforms display similar long-term evolutionary patterns, best described by the birth-and-death model of evolution. Notably, this observation is in contrast with the theoretical belief that clustered RD H1 genes evolve in a concerted manner. The split of the RI group from the main RD group must therefore have occurred before the divergence between vertebrates and invertebrates about 815 million years ago. This was the result of the transposition of H1 genes to solitary locations in the genome.Xunta de Galicia; 10PX110304Canadá. Canadian Institutes of Health Research; MOP-5771

Wind-aided flame spread under oblique forced flow

he wind-aided flame spread process along a solid fuel rod under oblique forced flow is analyzed in absence of gravity or when the forced flow dominates the gravity-induced flow. The transverse velocity is large enough to ensure that mixing of the fuel vapors and air occurs in a thin boundary layer surrounding the fuel rod and we can use the boundary layer approximation to describe the gas-phase chemical reaction and downwind flame spread process. A global, second-order, Arrhenius expression is employed to describe the gas-phase reaction, while the solid surface gasification reaction is modeled in terms of a constant pyrolysis temperature. The solid is heated by the hot gases convected from the flame by the axial component of the velocity in the direction of the flame spread. The solid will be considered thermally thick, assuming the thickness of the heated layer in the solid to be small compared with the rod radius. The analysis determines the flame spread velocity and the flow structure in the flame front region. The analysis also shows that flame spread is not possible at large flow velocities due to finite rate effects, while at low velocities the gas-phase reaction is diffusion-controlled. By including radiation losses from the surface a flame spread limit, at low velocities, is also found in the present analysis. The wind-aided flame spread process along a solid fuel rod under oblique forced flow is analyzed in absence of gravity or when the forced flow dominates the gravity-induced flow. The transverse velocity is large enough to ensure that mixing of the fuel vapors and air occurs in a thin boundary layer surrounding the fuel rod and we can use the boundary layer approximation to describe the gas-phase chemical reaction and downwind flame spread process. A global, second-order, Arrhenius expression is employed to describe the gas-phase reaction, while the solid surface gasification reaction is modeled in terms of a constant pyrolysis temperature. The solid is heated by the hot gases convected from the flame by the axial component of the velocity in the direction of the flame spread. The solid will be considered thermally thick, assuming the thickness of the heated layer in the solid to be small compared with the rod radius. The analysis determines the flame spread velocity and the flow structure in the flame front region. The analysis also shows that flame spread is not possible at large flow velocities due to finite rate effects, while at low velocities the gas-phase reaction is diffusion-controlled. By including radiation losses from the surface a flame spread limit, at low velocities, is also found in the present analysis

Tetrahydrobenzothiophene derivatives: conformationally restricted inhibitors of type II dehydroquinase

Restriction is good for inhibition! Tetrahydrobenzothiophene-derived rigid mimics of the type II dehydroquinase (DHQ2)-catalyzed reaction intermediate are reported. These derivatives fix the interaction with the tyrosine, the base that initiates the enzymatic reaction, in an inappropriate orientation for catalysis. Two competitive inhibitors in the series, 2-propenyl derivative 5 e and 2-cyclopropylethyl compound 5 i (shown), were crystallized in complex with DHQ2 from <i>Helicobacter pylori</i>, and the X-ray structures were determined at 1.95Å and 1.85Å, respectively