Fusion and Fission of Genes Define a Metric between Fungal Genomes

Gene fusion and fission events are key mechanisms in the evolution of gene architecture, whose effects are visible in protein architecture when they occur in coding sequences. Until now, the detection of fusion and fission events has been performed at the level of protein sequences with a post facto removal of supernumerary links due to paralogy, and often did not include looking for events defined only in single genomes. We propose a method for the detection of these events, defined on groups of paralogs to compensate for the gene redundancy of eukaryotic genomes, and apply it to the proteomes of 12 fungal species. We collected an inventory of 1,680 elementary fusion and fission events. In half the cases, both composite and element genes are found in the same species. Per-species counts of events correlate with the species genome size, suggesting a random mechanism of occurrence. Some biological functions of the genes involved in fusion and fission events are slightly over- or under-represented. As already noted in previous studies, the genes involved in an event tend to belong to the same functional category. We inferred the position of each event in the evolution tree of the 12 fungal species. The event localization counts for all the segments of the tree provide a metric that depicts the “recombinational” phylogeny among fungi. A possible interpretation of this metric as distance in adaptation space is proposed

Multiple Horizontal Gene Transfer Events and Domain Fusions Have Created Novel Regulatory and Metabolic Networks in the Oomycete Genome

Complex enzymes with multiple catalytic activities are hypothesized to have evolved from more primitive precursors. Global analysis of the Phytophthora sojae genome using conservative criteria for evaluation of complex proteins identified 273 novel multifunctional proteins that were also conserved in P. ramorum. Each of these proteins contains combinations of protein motifs that are not present in bacterial, plant, animal, or fungal genomes. A subset of these proteins were also identified in the two diatom genomes, but the majority of these proteins have formed after the split between diatoms and oomycetes. Documentation of multiple cases of domain fusions that are common to both oomycetes and diatom genomes lends additional support for the hypothesis that oomycetes and diatoms are monophyletic. Bifunctional proteins that catalyze two steps in a metabolic pathway can be used to infer the interaction of orthologous proteins that exist as separate entities in other genomes. We postulated that the novel multifunctional proteins of oomycetes could function as potential Rosetta Stones to identify interacting proteins of conserved metabolic and regulatory networks in other eukaryotic genomes. However ortholog analysis of each domain within our set of 273 multifunctional proteins against 39 sequenced bacterial and eukaryotic genomes, identified only 18 candidate Rosetta Stone proteins. Thus the majority of multifunctional proteins are not Rosetta Stones, but they may nonetheless be useful in identifying novel metabolic and regulatory networks in oomycetes. Phylogenetic analysis of all the enzymes in three pathways with one or more novel multifunctional proteins was conducted to determine the probable origins of individual enzymes. These analyses revealed multiple examples of horizontal transfer from both bacterial genomes and the photosynthetic endosymbiont in the ancestral genome of Stramenopiles. The complexity of the phylogenetic origins of these metabolic pathways and the paucity of Rosetta Stones relative to the total number of multifunctional proteins suggests that the proteome of oomycetes has few features in common with other Kingdoms

2009 Neurospora Bibliography

This bibliography represents my attempt to collect all works dealing substantially with Neurospora. Please let me know of anything published in 2008 or 2009 that is not included here or in the previous bibliography, so that it might be mentioned next year. I would be especially happy to hear of chapters from books, and articles from journals not indexed in major bibliographic services. Please also let me know of any errors in citation. Please send reprints or copies of articles to the Fungal Genetics Stock Center

Evolution at the Subgene Level: Domain Rearrangements in the Drosophila Phylogeny

Supplementary sections 1–13, tables S1–S10, and figures S1–S9 are available at Molecular Biology and Evolution online (http://www.mbe.oxfordjournals.org/).Although the possibility of gene evolution by domain rearrangements has long been appreciated, current methods for reconstructing and systematically analyzing gene family evolution are limited to events such as duplication, loss, and sometimes, horizontal transfer. However, within the Drosophila clade, we find domain rearrangements occur in 35.9% of gene families, and thus, any comprehensive study of gene evolution in these species will need to account for such events. Here, we present a new computational model and algorithm for reconstructing gene evolution at the domain level. We develop a method for detecting homologous domains between genes and present a phylogenetic algorithm for reconstructing maximum parsimony evolutionary histories that include domain generation, duplication, loss, merge (fusion), and split (fission) events. Using this method, we find that genes involved in fusion and fission are enriched in signaling and development, suggesting that domain rearrangements and reuse may be crucial in these processes. We also find that fusion is more abundant than fission, and that fusion and fission events occur predominantly alongside duplication, with 92.5% and 34.3% of fusion and fission events retaining ancestral architectures in the duplicated copies. We provide a catalog of ∼9,000 genes that undergo domain rearrangement across nine sequenced species, along with possible mechanisms for their formation. These results dramatically expand on evolution at the subgene level and offer several insights into how new genes and functions arise between species.National Science Foundation (U.S.) (Graduate Research Fellowship)National Science Foundation (U.S.) (CAREER award NSF 0644282

Exploring the Non-vertical Component of Bacterial Evolution Using Network Structures

The central tree metaphor has been challenged over the last couple of decades with the observation of incongruent trees derived largely from protein-coding genes in prokaryotic genomes. There are an increasing number of evolutionary processes and entities that confuse and confound the traditional understanding of evolution. As a result, these processes and entities are very often omitted from phylogenetic studies altogether. In this thesis I attempt to uncover the importance of non-tree like evolution. I discuss the types of genes that do not adhere to vertical patterns of inheritance such as fusion genes and mobile genetic elements. Furthermore I explore the alternative of using network structures in describing the evolutionary history of bacteria. This thesis recounts two key uses of networks for revealing the less commonly noted aspects of bacterial evolution. Firstly I present each stage in the development of a new method for identifying fusions of unrelated genes from conception of the idea, through the implementation to its application to data. Secondly I use networks of gene sharing to elucidate patterns of divergence among a group of closely related bacteria that would have once formed a single species cloud. These studies reveal an abundance of the types of genes that contradict traditional tree-thinking and support the notion that a strictly vertical view of evolution is inadequate when describing bacterial relationships

Studies on the Modular Evolution of Genes

Gene evolution is primarily studied through the observations of comparative cumulative point mutations between homologs. Genes also evolve through “remodelling”, the process of repurposing and reorganising genes and gene fragments into novel sequences. Gene remodelling is a relatively underappreciated evolutionary concept. Remodelling events circumscribe the development of novel sequences via fusion or fission events and through the shuffling of exons or domains. To date, all studies into remodelling have focussed on specific remodelling events, for example gene fusions in cancer samples, or have used small datasets (<15 species). As such, a comparative remodelling analyses between two taxonomic Kingdoms has yet to be completed. In 2018, CompositeSearch was developed to overcome the computational bottlenecks associated with mining all possible combinations that may attribute to remodelling events. We used CompositeSearch to investigate the comparative extent of remodelling within large fungal (107 species) and plant (50 species) datasets. We observed approximately 50% of fungal genes and 61% of plant genes to have a history of remodelling despite robust controls against Type I errors. We observed the rate of remodelled family birth and decay to be clocklike in both datasets, and that remodelled genes were considerably more homoplastic than non-remodelled genes. Functional overrepresentation analysis concluded that remodelled genes were associated with rapidly evolving systems, such as secondary metabolism, and with phenotypic novelty, such as flowering in angiosperms. Remodelling events have been associated with the development of antimicrobial resistance (AMR). As CompositeSearch does not discern between a fusion event and any other remodelling event, we developed CompositeBLAST to detect novel AMR fusion events. CompositeBLAST was considerably faster and more sensitive than previously published fusion detection tools. Using this software, we detected previously unreported mupirocin and vancomycin resistance genes as being derived from remodelling events

The evolutionary role of human-specific genomic events

In the short evolutionary time since the human-chimpanzee divergence, approximately 6.6 million years ago, humans have acquired a range of traits that are unique among primates. These include tripling brain size, enhanced cognitive abilities, complex culture, descended larynx structure that enables spoken language, longevity, specific diseases, inferior olfaction, and (in some human populations) adult lactase persistence. These traits were likely to have evolved through various genomic mechanisms, among them gene duplications and gene-culture co-evolution. Several studies have estimated the dates for some of these human lineage genomic events. However, no study to date has performed a genomewide estimate of the dates of all human gene duplications. Moreover, as many of these traits were likely to have evolved via gene-culture coevolutionary mechanisms, investigating the evolution of one of these human-specific traits – lactase persistence – provides a model example for in-depth future investigations of specific human phenotypes. In this study I have investigated an important class of human-specific genomic events – gene duplications (otherwise known as human inparalogues). I have developed a new bioinformatics approach for detecting human lineage-specific inparalogues and the duplication dates for those genes. I show that human-specific inparalogues are non-randomly distributed among biological function classes, and their duplication event dates are non-randomly distributed on a timeline between the date of the human-chimpanzee split and the present. I have also investigated the evolution of the human-specific polymorphic trait – lactase persistence. I have performed a worldwide correlation analysis comparing frequency data on all currently known lactase persistence-associated alleles and the distribution of the lactase persistence phenotype in different human populations. I have also performed a gene-culture co-evolution analysis, employing spatially explicit simulation and Approximate Bayesian Computation to condition simulations on genetic and archaeological data, in order to make inferences on the evolution of lactase persistence and dairying in Europe