Identification of multiple independent horizontal gene transfers into poxviruses using a comparative genomics approach

<p>Abstract</p> <p>Background</p> <p>Poxviruses are important pathogens of humans, livestock and wild animals. These large dsDNA viruses have a set of core orthologs whose gene order is extremely well conserved throughout poxvirus genera. They also contain many genes with sequence and functional similarity to host genes which were probably acquired by horizontal gene transfer.</p> <p>Although phylogenetic trees can indicate the occurrence of horizontal gene transfer and even uncover multiple events, their use may be hampered by uncertainties in both the topology and the rooting of the tree. We propose to use synteny conservation around the horizontally transferred gene (HTgene) to distinguish between single and multiple events.</p> <p>Results</p> <p>Here we devise a method that incorporates comparative genomic information into the investigation of horizontal gene transfer, and we apply this method to poxvirus genomes. We examined the synteny conservation around twenty four pox genes that we identified, or which were reported in the literature, as candidate HTgenes. We found support for multiple independent transfers into poxviruses for five HTgenes. Three of these genes are known to be important for the survival of the virus in or out of the host cell and one of them increases susceptibility to some antiviral drugs.</p> <p>Conclusion</p> <p>In related genomes conserved synteny information can provide convincing evidence for multiple independent horizontal gene transfer events even in the absence of a robust phylogenetic tree for the HTgene.</p

The potential of cell cultures for the production of salt tolerant cultivars.

The progress towards the production of salt tolerant plants through selection in cell cultures is briefly reviewed. The need for a fuller understanding of the mechanisms of salt tolerance in non-halophytes is emphasised and illustrated with reference to recent investigations on the role of proline. A clear protective effect, against salt stress, of exogenously applied proline has been demonstrated suggesting elevated levels of endogenous proline synthesis, for which there is a direct selection procedure, as a basis for improved salt tolerance. Salt tolerance of proline-overproducing plants and cell cultures is currently under investigation in a Nicotiana sylvestris line with almost 100-fold increase in free proline

Parking functions, labeled trees and DCJ sorting scenarios

In genome rearrangement theory, one of the elusive questions raised in recent years is the enumeration of rearrangement scenarios between two genomes. This problem is related to the uniform generation of rearrangement scenarios, and the derivation of tests of statistical significance of the properties of these scenarios. Here we give an exact formula for the number of double-cut-and-join (DCJ) rearrangement scenarios of co-tailed genomes. We also construct effective bijections between the set of scenarios that sort a cycle and well studied combinatorial objects such as parking functions and labeled trees.Comment: 12 pages, 3 figure

Phylogenomics: Gene Duplication, Unrecognized Paralogy and Outgroup Choice

Comparative genomics has revealed the ubiquity of gene and genome duplication and subsequent gene loss. In the case of gene duplication and subsequent loss, gene trees can differ from species trees, thus frequent gene duplication poses a challenge for reconstruction of species relationships. Here I address the case of multi-gene sets of putative orthologs that include some unrecognized paralogs due to ancestral gene duplication, and ask how outgroups should best be chosen to reduce the degree of non-species tree (NST) signal. Consideration of expected internal branch lengths supports several conclusions: (i) when a single outgroup is used, the degree of NST signal arising from gene duplication is either independent of outgroup choice, or is minimized by use of a maximally closely related post-duplication (MCRPD) outgroup; (ii) when two outgroups are used, NST signal is minimized by using one MCRPD outgroup, while the position of the second outgroup is of lesser importance; and (iii) when two outgroups are used, the ability to detect gene trees that are inconsistent with known aspects of the species tree is maximized by use of one MCRPD, and is either independent of the position of the second outgroup, or is maximized for a more distantly related second outgroup. Overall, these results generalize the utility of closely-related outgroups for phylogenetic analysis

2R and remodeling of vertebrate signal transduction engine

<p>Abstract</p> <p><b>Background</b></p> <p>Whole genome duplication (WGD) is a special case of gene duplication, observed rarely in animals, whereby all genes duplicate simultaneously through polyploidisation. Two rounds of WGD (2R-WGD) occurred at the base of vertebrates, giving rise to an enormous wave of genetic novelty, but a systematic analysis of functional consequences of this event has not yet been performed.</p> <p><b>Results</b></p> <p>We show that 2R-WGD affected an overwhelming majority (74%) of signalling genes, in particular developmental pathways involving receptor tyrosine kinases, Wnt and transforming growth factor-β ligands, G protein-coupled receptors and the apoptosis pathway. 2R-retained genes, in contrast to tandem duplicates, were enriched in protein interaction domains and multifunctional signalling modules of Ras and mitogen-activated protein kinase cascades. 2R-WGD had a fundamental impact on the cell-cycle machinery, redefined molecular building blocks of the neuronal synapse, and was formative for vertebrate brains. We investigated 2R-associated nodes in the context of the human signalling network, as well as in an inferred ancestral pre-2R (AP2R) network, and found that hubs (particularly involving negative regulation) were preferentially retained, with high connectivity driving retention. Finally, microarrays and proteomics demonstrated a trend for gradual paralog expression divergence independent of the duplication mechanism, but inferred ancestral expression states suggested preferential subfunctionalisation among 2R-ohnologs (2ROs).</p> <p><b>Conclusions</b></p> <p>The 2R event left an indelible imprint on vertebrate signalling and the cell cycle. We show that 2R-WGD preferentially retained genes are associated with higher organismal complexity (for example, locomotion, nervous system, morphogenesis), while genes associated with basic cellular functions (for example, translation, replication, splicing, recombination; with the notable exception of cell cycle) tended to be excluded. 2R-WGD set the stage for the emergence of key vertebrate functional novelties (such as complex brains, circulatory system, heart, bone, cartilage, musculature and adipose tissue). A full explanation of the impact of 2R on evolution, function and the flow of information in vertebrate signalling networks is likely to have practical consequences for regenerative medicine, stem cell therapies and cancer treatment.</p

Complete Genome Viral Phylogenies Suggests the Concerted Evolution of Regulatory Cores and Accessory Satellites

We consider the concerted evolution of viral genomes in four families of DNA viruses. Given the high rate of horizontal gene transfer among viruses and their hosts, it is an open question as to how representative particular genes are of the evolutionary history of the complete genome. To address the concerted evolution of viral genes, we compared genomic evolution across four distinct, extant viral families. For all four viral families we constructed DNA-dependent DNA polymerase-based (DdDp) phylogenies and in addition, whole genome sequence, as quantitative descriptions of inter-genome relationships. We found that the history of the polymerase gene was highly predictive of the history of the genome as a whole, which we explain in terms of repeated, co-divergence events of the core DdDp gene accompanied by a number of satellite, accessory genetic loci. We also found that the rate of gene gain in baculovirus and poxviruses proceeds significantly more quickly than the rate of gene loss and that there is convergent acquisition of satellite functions promoting contextual adaptation when distinct viral families infect related hosts. The congruence of the genome and polymerase trees suggests that a large set of viral genes, including polymerase, derive from a phylogenetically conserved core of genes of host origin, secondarily reinforced by gene acquisition from common hosts or co-infecting viruses within the host. A single viral genome can be thought of as a mutualistic network, with the core genes acting as an effective host and the satellite genes as effective symbionts. Larger virus genomes show a greater departure from linkage equilibrium between core and satellites functions

Representativeness of microsatellite distributions in genomes, as revealed by 454 GS-FLX Titanium pyrosequencing

<p>Abstract</p> <p>Background</p> <p>Microsatellites are markers of choice in population genetics and genomics, as they provide useful insight into patterns and processes as diverse as genome evolutionary dynamics and demographic processes. The acquisition of microsatellites through multiplex-enriched libraries and 454 GS-FLX Titanium pyrosequencing is a promising new tool for the isolation of new markers in unknown genomes. This approach can also be used to evaluate the extent to which microsatellite-enriched libraries are representative of the genome from which they were isolated. In this study, we deciphered potential discrepancies in microsatellite content recovery for two reference genomes (<it>Apis mellifera </it>and <it>Danio rerio</it>), selected on the basis of their extreme heterogeneity in terms of the proportions and distributions of microsatellites on chromosomes.</p> <p>Results</p> <p>The <it>A. mellifera </it>genome, in particular, was found to be highly heterogeneous, due to extremely high rates of recombination, with hotspots, but the only bias consistently introduced into pyrosequenced multiplex-enriched libraries concerned sequence length, with the overrepresentation of sequences 160 to 320 bp in length. Other deviations from expected proportions or distributions of motifs on chromosomes were observed, but the significance and intensity of these deviations was mostly limited. Furthermore, no consistent adverse competition between multiplexed probes was observed during the motif enrichment phase.</p> <p>Conclusions</p> <p>This approach therefore appears to be a promising strategy for improving the development of microsatellites, as it introduces no major bias in terms of the proportions and distribution of microsatellites.</p

Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?

BACKGROUND: Medical and pre-professional health students ask questions about human health that can be answered in two ways, by giving proximate and evolutionary explanations. Proximate explanations, most common in textbooks and classes, describe the immediate scientifically known biological mechanisms of anatomical characteristics or physiological processes. These explanations are necessary but insufficient. They can be complemented with evolutionary explanations that describe the evolutionary processes and principles that have resulted in human biology we study today. The main goal of the science of Darwinian Medicine is to investigate human disease, disorders, and medical complications from an evolutionary perspective. DISCUSSION: This paper contrasts the differences between these two types of explanations by describing principles of natural selection that underlie medical questions. Thus, why is human birth complicated? Why does sickle cell anemia exist? Why do we show symptoms like fever, diarrhea, and coughing when we have infection? Why do we suffer from ubiquitous age-related diseases like arteriosclerosis, Alzheimer's and others? Why are chronic diseases like type II diabetes and obesity so prevalent in modern society? Why hasn't natural selection eliminated the genes that cause common genetic diseases like hemochromatosis, cystic fibrosis, Tay sachs, PKU and others? SUMMARY: In giving students evolutionary explanations professors should underscore principles of natural selection, since these can be generalized for the analysis of many medical questions. From a research perspective, natural selection seems central to leading hypotheses of obesity and type II diabetes and might very well explain the occurrence of certain common genetic diseases like cystic fibrosis, hemochromatosis, Tay sachs, Fragile X syndrome, G6PD and others because of their compensating advantages. Furthermore, armed with evolutionary explanations, health care professionals can bring practical benefits to patients by treating their symptoms of infection more specifically and judiciously. They might also help curtail the evolutionary arms race between pathogens and antibiotic defenses