The genome of the medieval Black Death agent (extended abstract)

The genome of a 650 year old Yersinia pestis bacteria, responsible for the medieval Black Death, was recently sequenced and assembled into 2,105 contigs from the main chromosome. According to the point mutation record, the medieval bacteria could be an ancestor of most Yersinia pestis extant species, which opens the way to reconstructing the organization of these contigs using a comparative approach. We show that recent computational paleogenomics methods, aiming at reconstructing the organization of ancestral genomes from the comparison of extant genomes, can be used to correct, order and complete the contig set of the Black Death agent genome, providing a full chromosome sequence, at the nucleotide scale, of this ancient bacteria. This sequence suggests that a burst of mobile elements insertions predated the Black Death, leading to an exceptional genome plasticity and increase in rearrangement rate.Comment: Extended abstract of a talk presented at the conference JOBIM 2013, https://colloque.inra.fr/jobim2013_eng/. Full paper submitte

Ancestral Gene Synteny Reconstruction Improves Extant Species Scaffolding

We exploit the methodological similarity between ancestral genome reconstruction and extant genome scaffolding. We present a method, called ARt-DeCo that constructs neighborhood relationships between genes or contigs, in both ancestral and extant genomes, in a phylogenetic context. It is able to handle dozens of complete genomes, including genes with complex histories, by using gene phylogenies reconciled with a species tree, that is, annotated with speciation, duplication and loss events. Reconstructed ancestral or extant synteny comes with a support computed from an exhaustive exploration of the solution space. We compare our method with a previously published one that follows the same goal on a small number of genomes with universal unicopy genes. Then we test it on the whole Ensembl database, by proposing partial ancestral genome structures, as well as a more complete scaffolding for many partially assembled genomes on 69 eukaryote species. We carefully analyze a couple of extant adjacencies proposed by our method, and show that they are indeed real links in the extant genomes, that were missing in the current assembly. On a reduced data set of 39 eutherian mammals, we estimate the precision and sensitivity of ARt-DeCo by simulating a fragmentation in some well assembled genomes, and measure how many adjacencies are recovered. We find a very high precision, while the sensitivity depends on the quality of the data and on the proximity of closely related genomes

The Glanville fritillary genome retains ancient karyotype and reveals selective chromosomal fusions in Lepidoptera

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Phylogenetic assembly of paleogenomes integrating ancient DNA data

Luhmann N. Phylogenetic assembly of paleogenomes integrating ancient DNA data. Bielefeld: Universität Bielefeld; 2017.In comparative genomics, reconstructing the genomes of ancestral species in a given phylogeny is an important problem in order to analyze genome evolution over time. The diversity of present-day genomes in terms of local mutations and genome rearrangements allows to shed light on the dynamics of evolutionary processes that led from a common ancestor to a set of extant genomes. This speciation history is depicted in a phylogenetic tree. Comparative genome reconstruction methods aim to infer genomic features such as an order of markers (e.g. genes) for extinct species at internal nodes of the tree by applying different evolutionary models, relying only on the information available for the extant genomes at the leaves of the phylogenetic tree. Recently, the steady progress in sequencing technologies led to the emergence of the field of paleogenomics, where the study of ancient DNA (aDNA) found in conserved organic material is moving rapidly towards the sequencing and analysis of complete paleogenomes. Such ''genetic time travel'' allows direct insight into specific phases of the evolution of specific genomes that are not only implicitly inferred from extant DNA sequences. However, as DNA is naturally degraded over time after the death of an organism and environmental conditions interfere with the conservation of DNA material, an assembly of these paleogenomes is usually fragmented, preventing a detailed analysis of genome rearrangements along the branches of the phylogenetic tree. In this thesis, we aim to combine the study of aDNA and comparative ancestral reconstruction in a phylogenetic framework. The comparison with extant related genomes can naturally assist in scaffolding a fragmented aDNA assembly, while the aDNA sequencing data can be included as an additional source of information for comparative reconstruction methods to improve the reconstructions of all related genomes in the phylogenetic tree. Our first focus is on integrative methods to reconstruct marker orders globally in a phylogeny under the assumption of parsimony. An underlying rearrangement model can describe the evolutionary operations that occurred along the edges of the tree. However, as much as complex rearrangement scenarios can give insights into underlying biological mechanisms during evolution, from an computational point of view the ancestral reconstruction problem under rearrangement distances is an NP-hard problem. One exception is the Single-Cut-or-Join (SCJ) distance, that uses a marker order-based representation of the involved genomes to model the cut and join of marker adjacencies as evolutionary operations. We build upon this rearrangement model and describe parsimony-based reconstruction methods aiming to minimize the SCJ distance in the tree. In addition, we require the reconstructed solutions to be consistent, such that they represent linear or circular regions of the ancestral genome. Our first polynomial-time method is based on the Sankoff-Rousseau algorithm and directly includes an aDNA assembly graph at one internal node of the tree. We show that including branch lengths in the underlying tree can avoid ambiguity in practice. Our second approach follows a more general strategy and includes the aDNA sequencing data as local weights for adjacencies next to the SCJ distance in the objective. We describe a fixed-parameter-tractable algorithm that also allows to sample co-optimal solutions. Finally, we describe an approach to fill gaps between potentially adjacent markers by aDNA data to reconstruct the complete genome sequence of a paleogenome guided by the related extant genome sequences. In addition, this approach enables us to select the adjacencies that are supported by the sequencing information from sets of conflicting adjacencies. We evaluate our proposed models and algorithms on simulated and biological data. In particular, we integrate two aDNA sequencing data sets for ancient strains of the pathogen Yersinia pestis, that is understood to be the cause of several pandemics in medieval times. We show that the combination of aDNA sequencing reads and a parsimonious reconstruction in the phylogenetic tree reduces the fragmentation of an initial aDNA assembly substantially and explore alternative reconstructions to emphasize reliably reconstructed regions of the ancient genomes

The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera

Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n=31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n=31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.Marie Curie International Fellowship (PIOF-GA-2011-303312

The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera

Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n¼31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n¼31 for at least 140My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths