Dynamics of Genome Rearrangement in Bacterial Populations

Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of “symmetric inversions”—inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings represent the first characterization of genome arrangement evolution in a bacterial population evolving outside laboratory conditions. Insight into the process of genomic rearrangement may further the understanding of pathogen population dynamics and selection on the architecture of circular bacterial chromosomes

Generation of Two-Voice Imitative Counterpoint from Statistical Models

Generating new music based on rules of counterpoint has been deeply studied in music informatics. In this article, we try to go further, exploring a method for generating new music based on the style of Palestrina, based on combining statistical generation and pattern discovery. A template piece is used for pattern discovery, and the patterns are selected and organized according to a probabilistic distribution, using horizontal viewpoints to describe melodic properties of events. Once the template is covered with patterns, two-voice counterpoint in a florid style is generated into those patterns using a first-order Markov model. The template method solves the problem of coherence and imitation never addressed before in previous research in counterpoint music generation. For constructing the Markov model, vertical slices of pitch and rhythm are compiled over a large corpus of dyads from Palestrina masses. The template enforces different restrictions that filter the possible paths through the generation process. A double backtracking algorithm is implemented to handle cases where no solutions are found at some point within a generation path. Results are evaluated by both information content and listener evaluation, and the paper concludes with a proposed relationship between musical quality and information content. Part of this research has been presented at SMC 2016 in Hamburg, Germany

Clustering and graph mining techniques for classification of complex structural variations in cancer genomes

For many years, a major question in cancer genomics has been the identification of those variations that can have a functional role in cancer, and distinguish from the majority of genomic changes that have no functional consequences. This is particularly challenging when considering complex chromosomal rearrangements, often composed of multiple DNA breaks, resulting in difficulties in classifying and interpreting them functionally. Despite recent efforts towards classifying structural variants (SVs), more robust statistical frames are needed to better classify these variants and isolate those that derive from specific molecular mechanisms. We present a new statistical approach to analyze SVs patterns from 2392 tumor samples from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium and identify significant recurrence, which can inform relevant mechanisms involved in the biology of tumors. The method is based on recursive KDE clustering of 152,926 SVs, randomization methods, graph mining techniques and statistical measures. The proposed methodology was able not only to identify complex patterns across different cancer types but also to prove them as not random occurrences. Furthermore, a new class of pattern that was not previously described has been identified.Among others, this study has been supported by projects: SAF2017-89450-R (TransTumVar) and PID2020-119797RB-100 (BenchSV) from Science and Innovation Spanish Minstry. It has also been supported by the Spanish Goverment (contract PID2019-107255GB), Generalitat de Catalunya (contract 2014-SGR-1051) and Universitat Politècnica de Catalunya (45-FPIUPC2018).Peer ReviewedPostprint (published version

Supergenes and complex phenotypes.

Understanding the molecular underpinnings of evolutionary adaptations is a central focus of modern evolutionary biology. Recent studies have uncovered a panoply of complex phenotypes, including locally adapted ecotypes and cryptic morphs, divergent social behaviours in birds and insects, as well as alternative metabolic pathways in plants and fungi, that are regulated by clusters of tightly linked loci. These 'supergenes' segregate as stable polymorphisms within or between natural populations and influence ecologically relevant traits. Some supergenes may span entire chromosomes, because selection for reduced recombination between a supergene and a nearby locus providing additional benefits can lead to locus expansions with dynamics similar to those known for sex chromosomes. In addition to allowing for the co-segregation of adaptive variation within species, supergenes may facilitate the spread of complex phenotypes across species boundaries. Application of new genomic methods is likely to lead to the discovery of many additional supergenes in a broad range of organisms and reveal similar genetic architectures for convergently evolved phenotypes

Evolution of the Rdr1 TNL-cluster in roses and other Rosaceous species

Background: The resistance of plants to pathogens relies on two lines of defense: a basal defense response and a pathogen-specific system, in which resistance (R) genes induce defense reactions after detection of pathogen-associated molecular patterns (PAMPS). In the specific system, a so-called arms race has developed in which the emergence of new races of a pathogen leads to the diversification of plant resistance genes to counteract the pathogens' effect. The mechanism of resistance gene diversification has been elucidated well for short-lived annual species, but data are mostly lacking for long-lived perennial and clonally propagated plants, such as roses. We analyzed the rose black spot resistance gene, Rdr1, in five members of the Rosaceae: Rosa multiflora, Rosa rugosa, Fragaria vesca (strawberry), Malus x domestica (apple) and Prunus persica (peach), and we present the deduced possible mechanism of R-gene diversification.Results: We sequenced a 340.4-kb region from R. rugosa orthologous to the Rdr1 locus in R. multiflora. Apart from some deletions and rearrangements, the two loci display a high degree of synteny. Additionally, less pronounced synteny is found with an orthologous locus in strawberry but is absent in peach and apple, where genes from the Rdr1 locus are distributed on two different chromosomes. An analysis of 20 TIR-NBS-LRR (TNL) genes obtained from R. rugosa and R. multiflora revealed illegitimate recombination, gene conversion, unequal crossing over, indels, point mutations and transposable elements as mechanisms of diversification.A phylogenetic analysis of 53 complete TNL genes from the five Rosaceae species revealed that with the exception of some genes from apple and peach, most of the genes occur in species-specific clusters, indicating that recent TNL gene diversification began prior to the split of Rosa from Fragaria in the Rosoideae and peach from apple in the Spiraeoideae and continued after the split in individual species. Sequence similarity of up to 99% is obtained between two R. multiflora TNL paralogs, indicating a very recent duplication.Conclusions: The mechanisms by which TNL genes from perennial Rosaceae diversify are mainly similar to those from annual plant species. However, most TNL genes appear to be of recent origin, likely due to recent duplications, supporting the hypothesis that TNL genes in woody perennials are generally younger than those from annuals. This recent origin might facilitate the development of new resistance specificities, compensating for longer generation times in woody perennials.DFG/DE 511/4-1DFG/DE 511/4-

Genetic differentiation of two species of buckwheat (Eriogonum)

Limestone mining in the San Franicso Mountain Range of west central Utah threatens the survival of a rare endemic species of buckwheat (Eriogonum soredium). This species is an edaphic endemic, only found growing on the outcrops of the Ordovician limestone mines in the area. Eriogonum soredium is a candidate for governmental protection under the Endangered Species Act (ESA). However, a common, widespread buckwheat (Eriogonum shockleyi) appears to be closely related to the narrow endemic. The genetic relatedness of the rare and and common species will greatly influence the decision of United States Fish and Wildlife Service (USFW)of whether or not to list the rare species for governmental protection. This study investiaged the amount of genetic divergence between the two species to facilitate the decision. I found levels of population divergence intermediate between a state of no genetic distinction, and complete genetic divergence. However, the two species fall near the genetic divergence end of the continuum. This situation is not uncommon in plants, and suggests that the two species are currently in the process of speciation. Considering their morphological differences, and the ability of the genus Eriogonum to hybridize, these two species show significant amounts of divergence. These results suggest that the continued treatment of E. soredium as distinct from E. shcokelyi is warranted. The USFW will use the results of this study to aid their decision of whether or not to list E. soredium under the ESA. Should the species be listed for protection under the ESA, limitations to the expansion of limestone mining in the San Francisco Mountain Range will be considered

Language and Automata Theory and Applications

International audienc