Approches algorithmiques pour l’inférence d’histoires de duplication en tandem avec inversions et délétions pour des familles multigéniques

[Français] Une fraction importante des génomes eucaryotes est constituée de Gènes Répétés en Tandem (GRT). Un mécanisme fondamental dans l’évolution des GRT est la recombinaison inégale durant la méiose, entrainant la duplication locale (en tandem) de segments chromosomiques contenant un ou plusieurs gènes adjacents. Différents algorithmes ont été proposés pour inférer une histoire de duplication en tandem pour un cluster de GRT. Cependant, leur utilisation est limitée dans la pratique, car ils ne tiennent pas compte d’autres événements évolutifs pourtant fréquents, comme les inversions, les duplications inversées et les délétions. Cette thèse propose différentes approches algorithmiques permettant d’intégrer ces événements dans le modèle de duplication en tandem classique. Nos contributions sont les suivantes: • Intégrer les inversions dans un modèle de duplication en tandem simple (duplication d’un gène à la fois) et proposer un algorithme exact permettant de calculer le nombre minimal d’inversions s’étant produites dans l’évolution d’un cluster de GRT. • Généraliser ce modèle pour l’étude d’un ensemble de clusters orthologues dans plusieurs espèces. • Proposer un algorithme permettant d’inférer l’histoire évolutive d’un cluster de GRT en tenant compte des duplications en tandem, duplications inversées, inversions et délétions de segments chromosomiques contenant un ou plusieurs gènes adjacents.[English] Tandemly arrayed genes (TAGs) represent an important fraction of most genomes. A fundamental mechanism at the origin of TAG clusters is unequal crossing-over during meiosis, leading to the duplication of chromosomal segments containing one or many adjacent genes. Such duplications are called tandem duplications, as the duplicated segment is placed next to the original one on the chromosome. Different algorithms have been proposed to infer the tandem duplication history of a TAG cluster. However, their applicability is limited in practice since they do not take into account other frequent evolutionary events such as inversion, inverted duplication and deletion. In this thesis, we propose different algorithmic approaches allowing to integrate these evolutionary events in the original tandem duplication model of evolution. Our contributions are summarized as follows: • We integrate inversion events in a tandem duplication model restricted to single gene duplications, and we propose an exact algorithm allowing to compute the minimum number of inversions explaining the evolution of a TAG cluster. • We generalize this model to the study of orthologous TAG clusters in different species. • We propose an algorithm allowing to infer the evolutionary history of a TAG cluster through tandem duplication, inverted duplication, inversion and deletion of chromosomal segments containing one or many adjacent genes

The Blue Stragglers of the Old Open Cluster NGC 188

The old (7 Gyr) open cluster NGC 188 has yielded a wealth of astrophysical insight into its rich blue straggler population. Specifically, the NGC 188 blue stragglers are characterized by: A binary frequency of 80% for orbital periods less than $10^4$ days;Typical orbital periods around 1000 days;Typical secondary star masses of 0.5 M$_{\odot}$; At least some white dwarf companion stars; Modestly rapid rotation; A bimodal radial spatial distribution; Dynamical masses greater than standard stellar evolution masses (based on short-period binaries); Under-luminosity for dynamical masses (short-period binaries). Extensive $N$-body modeling of NGC 188 with empirical initial conditions reproduces the properties of the cluster, and in particular the main-sequence solar-type binary population. The current models also reproduce well the binary orbital properties of the blue stragglers, but fall well short of producing the observed number of blue stragglers. This deficit could be resolved by reducing the frequency of common-envelope evolution during Roche lobe overflow. Both the observations and the $N$-body models strongly indicate that the long-period blue-straggler binaries - which dominate the NGC 188 blue straggler population - are formed by asymptotic-giant (primarily) and red-giant mass transfer onto main sequence stars. The models suggest that the few non-velocity-variable blue stragglers formed from mergers or collisions. Several remarkable short-period double-lined binaries point to the importance of subsequent dynamical exchange encounters, and provide at least one example of a likely collisional origin for a blue straggler.Comment: Chapter 3, in Ecology of Blue Straggler Stars, H.M.J. Boffin, G. Carraro & G. Beccari (Eds), Astrophysics and Space Science Library, Springe

F.A.R.O.G. FORUM, Vol. 6 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1065/thumbnail.jp

Inferring evolutionary history of gene clusters from phlogenetic and gene order data

Gene duplication is frequent within gene clusters and plays a fundamental role in evolution by providing a source of new genetic material upon which natural selection can act. Although classical phylogenetic inference methods provide some insight into the evolutionary history of a gene cluster, they are not sufficient alone to differentiate single- from multiple gene duplication events and to answer other questions regarding the nature and size of evolutionary events. In this paper, we present an algorithm allowing to infer a set of optimal evolutionary histories for a gene cluster in a single species, according to a general cost model involving variable length duplications (in tandem or inverted), deletions, and inversions. We applied our algorithm to the human olfactory receptor and protocadherin gene clusters, showing that the duplication size distribution differs significantly between the two gene families. The algorithm is available through a web interface at http://www-lbit.iro.umontreal.ca/DILTAG/

An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation

Background: Lung maturation is a late fetal developmental event in both mice and humans. Because of this, lung immaturity is a serious problem in premature infants. Disruption of genes for either the glucocorticoid receptor (Nr3c1) or the NFIB transcription factors results in perinatal lethality due to lung immaturity. In both knockouts, the phenotype includes excess cell proliferation, failure of saccularization and reduced expression of markers of epithelial differentiation. This similarity suggests that the two genes may co-regulate a specific set of genes essential for lung maturation.Results: We analyzed the roles of these two transcription factors in regulating transcription using ChIP-seq data for NFIB, and RNA expression data and motif analysis for both. Our new ChIP-seq data for NFIB in lung at E16.5 shows that NFIB binds to a NFI motif. This motif is over-represented in the promoters of genes that are under-expressed in Nfib-KO mice at E18.5, suggesting an activator role for NFIB. Using available microarray data from Nr3c1-KO mice, we further identified 52 genes that are under-expressed in both Nfib and Nr3c1 knockouts, an overlap which is 13.1 times larger than what would be expected by chance. Finally, we looked for enrichment of 738 recently published transcription factor motifs in the promoters of these putative target genes and found that the NFIB and glucocorticoid receptor motifs were among the most enriched, suggesting that a subset of these genes may be directly activated by Nfib and Nr3c1.Conclusions: Our data provide the first evidence for Nfib and Nr3c1 co-regulating genes related to lung maturation. They also establish that the in vivo DNA-binding specificity of NFIB is the same as previously seen in vitro, and highly similar to that of the other NFI-family members NFIA, NFIC and NFIX

The Artiodactyl \u3ci\u3eAPOBEC3\u3c/i\u3e Innate Immune Repertoire Shows Evidence for a Multi-Functional Domain Organization that Existed in the Ancestor of Placental Mammals

Background: APOBEC3 (A3) proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinccoordinating motifs (Z1, Z2 or Z3). The presence of one A3 gene in mice (Z2–Z3) and seven in humans, A3A-H (Z1a, Z2a-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3), suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Results: Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals). This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. Conclusion: The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions) were selected by ancient pathogenic retrovirus infections