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

Duplicability of self-interacting human genes

BACKGROUND There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.At the time of publication the author Pérez-Bercoff was affiliated with Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin

Evolution of vertebrate genome organisation

THESIS 6713The increasing availability of genomic sequences from different vertebrate organisms affords molecular biologists the opportunity to thoroughly investigate phenomena that were only hinted at by more sparse data. The work described in this thesis develops the use of inter-and intra-genomic sequence comparisons to examine genome evolution through changes in genome arrangement and content. The vertebrate Fugu rubrupies (puffer?sh) has a small genome with little repetitive sequence which makes it attractive as a model genome. Its genome compaction and synteny conservation relative to the human genome were studied using data from public databases. The compaction of this genome was measured by comparing lengths of orthologous Fugu and human introns. Analysis of orthologous introns showed an eight-fold average size reduction in Fugu, consistent with the ratio of total genome sizes. There was no consistent pattern relating the size reduction in individual introns or genes to gene base composition in either species. For genes that are neighbours in Fugu, 40-50% have conserved synteny with a human chromosome. Comparison of observed data to computer simulations suggests that 4,000-16,000 chromosomal rearrangements have occurred since Fugu and human shared a common ancestor, implying a faster rate of rearrangement than seen in human/mouse comparisons. Intragenomic comparisons were used to examine the draft human genome sequence for evidence of ancient genomic duplications, by a combination of a map-based and a phylogeny-based approach. Evidence was found for extensive paralogy regions situated throughout the genome. Statistical analyses of these regions indicated that they were formed by en bloc duplication events. Molecular clock analysis of 191 gene families in the human genome indicates that a burst of gene duplication activity took place approximately 333-583 Mya, spanning the estimated time of origin of vertebrates (about 500 Mya). Moreover, more gene pairs of this age are found in paralogous regions than pairs that duplicated earlier or later. These results support the contention that many vertebrate gene families were formed by extensive duplication events, perhaps polyploidy, in an early chordate, and indicate that extensive genome rearrangement may have occurred following genome duplication

The deceptive simplicity of mendelian genetics

Mendel, a genius experimentalist, meticulously uncovered the genetic basis of heredity in work that transformed the science of biology. But does the alluring simplicity of Mendel’s laws sometimes obscure the true complexity of genetics? Gregor Mendel meticulously uncovered the genetic basis of heredity in work that transformed the science of biology. But does the alluring simplicity of Mendel’s laws sometimes obscure the true complexity of genetics