Cluster J Mycobacteriophages: Intron Splicing in Capsid and Tail Genes

Bacteriophages isolated on Mycobacterium smegmatis mc2155 represent many distinct genomes sharing little or no DNA sequence similarity. The genomes are architecturally mosaic and are replete with genes of unknown function. A new group of genomes sharing substantial nucleotide sequences constitute Cluster J. The six mycobacteriophages forming Cluster J are morphologically members of the Siphoviridae, but have unusually long genomes ranging from 106.3 to 117 kbp. Reconstruction of the capsid by cryo-electron microscopy of mycobacteriophage BAKA reveals an icosahedral structure with a triangulation number of 13. All six phages are temperate and homoimmune, and prophage establishment involves integration into a tRNA-Leu gene not previously identified as a mycobacterial attB site for phage integration. The Cluster J genomes provide two examples of intron splicing within the virion structural genes, one in a major capsid subunit gene, and one in a tail gene. These genomes also contain numerous free-standing HNH homing endonuclease, and comparative analysis reveals how these could contribute to genome mosaicism. The unusual Cluster J genomes provide new insights into phage genome architecture, gene function, capsid structure, gene mobility, intron splicing, and evolution. © 2013 Pope et al

The self-organization of genomes

Menzerath-Altmann law is a general law of human language stating, for instance, that the longer a word, the shorter its syllables. With the metaphor that genomes are words and chromosomes are syllables, we examine if genomes also obey the law. We find that longer genomes tend to be made of smaller chromosomes in organisms from three different kingdoms: fungi, plants, and animals. Our findings suggest that genomes self-organize under principles similar to those of human language.Peer ReviewedPostprint (author's final draft

Estimating translational selection in Eukaryotic Genomes

Natural selection on codon usage is a pervasive force that acts on a large variety of prokaryotic and eukaryotic genomes. Despite this, obtaining reliable estimates of selection on codon usage has proved complicated, perhaps due to the fact that the selection coefficients involved are very small. In this work, a population genetics model is used to measure the strength of selected codon usage bias, S, in 10 eukaryotic genomes. It is shown that the strength of selection is closely linked to expression and that reliable estimates of selection coefficients can only be obtained for genes with very similar expression levels. We compare the strength of selected codon usage for orthologous genes across all 10 genomes classified according to expression categories. Fungi genomes present the largest S values (2.24–2.56), whereas multicellular invertebrate and plant genomes present more moderate values (0.61–1.91). The large mammalian genomes (human and mouse) show low S values (0.22–0.51) for the most highly expressed genes. This might not be evidence for selection in these organisms as the technique used here to estimate S does not properly account for nucleotide composition heterogeneity along such genomes. The relationship between estimated S values and empirical estimates of population size is presented here for the first time. It is shown, as theoretically expected, that population size has an important role in the operativity of translational selection

Toward 959 nematode genomes

The sequencing of the complete genome of the nematode Caenorhabditis elegans was a landmark achievement and ushered in a new era of whole-organism, systems analyses of the biology of this powerful model organism. The success of the C. elegans genome sequencing project also inspired communities working on other organisms to approach genome sequencing of their species. The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla

The Mathematics of Phylogenomics

The grand challenges in biology today are being shaped by powerful high-throughput technologies that have revealed the genomes of many organisms, global expression patterns of genes and detailed information about variation within populations. We are therefore able to ask, for the first time, fundamental questions about the evolution of genomes, the structure of genes and their regulation, and the connections between genotypes and phenotypes of individuals. The answers to these questions are all predicated on progress in a variety of computational, statistical, and mathematical fields. The rapid growth in the characterization of genomes has led to the advancement of a new discipline called Phylogenomics. This discipline results from the combination of two major fields in the life sciences: Genomics, i.e., the study of the function and structure of genes and genomes; and Molecular Phylogenetics, i.e., the study of the hierarchical evolutionary relationships among organisms and their genomes. The objective of this article is to offer mathematicians a first introduction to this emerging field, and to discuss specific mathematical problems and developments arising from phylogenomics.Comment: 41 pages, 4 figure