Séquence homologue | EPFL Graph Search

En biologie moléculaire, les séquences homologues sont deux ou plusieurs séquences nucléotidiques partageant une origine évolutive commune, c'est-à-dire présentant une homologie au sens de l'évolution moléculaire. Deux segments d'ADN distincts sont susceptibles d'avoir une origine commune à la suite d'une spéciation (orthologie), d'une duplication (paralogie) ou d'un transfert horizontal de gènes. L'homologie de l'ADN, de l'ARN et des protéines est généralement déduite de similitudes de la séquence des acides nucléiques ou des peptides traduits : de fortes similitudes entre séquences sont l'indication d'une origine commune. Les techniques d'alignement de séquences multiples permettent de préciser quelles régions de chaque séquence sont homologues. redresse=3|centré|vignette| Alignement de séquences produit par à partir d'histones de mammifères. Les séquences représentées correspondent aux résidus d'acides aminés 120 à 180 de chacune de ces protéines. Les résidus conservés à travers t

Homoeolog Inference Methods Requiring Bidirectional Best Hits or Synteny Miss Many Pairs

Shaoline Sheppard

Homoeologs are pairs of genes or chromosomes in the same species that originated by speciation and were brought back together in the same genome by allopolyploidization. Bioinformatic methods for accurate homoeology inference are crucial for studying the evolutionary consequences of polyploidization, and homoeology is typically inferred on the basis of bidirectional best hit (BBH) and/or positional conservation (synteny). However, these methods neglect the fact that genes can duplicate and move, both prior to and after the allopolyploidization event. These duplications and movements can result in many-to-many and/or nonsyntenic homoeologs-which thus remain undetected and unstudied. Here, using the allotetraploid upland cotton (Gossypium hirsutum) as a case study, we show that conventional approaches indeed miss a substantial proportion of homoeologs. Additionally, we found that many of the missed pairs of homoeologs are broadly and highly expressed. A gene ontology analysis revealed a high proportion of the nonsyntenic and non-BBH homoeologs to be involved in protein translation and are likely to contribute to the functional repertoire of cotton. Thus, from an evolutionary and functional genomics standpoint, choosing a homoeolog inference method which does not solely rely on 1:1 relationship cardinality or synteny is crucial for not missing these potentially important homoeolog pairs.

OXFORD UNIV PRESS2021

Evolution of nucleosomes position in yeasts: conservation of global pattern and divergence of gene-specific patterns

Sébastien Dubuis

This master project describes computational analysis of nucleosomes positioning in four yeast species: S. cerevisiae, S. kudriavzevii, S. bayanus (three relatively close species, ~75% of sequence similarity) and C. glabrata (more distant, ~57% of sequence similarity). We found that the global organization of nucleosomes previously described in S. cerevisiae (Nucleosome Depleted Region followed by an array of nucleosomes) was largely conserved among the different species also with the conservation of occupied/depleted promoters' classification from previous works redefined here in a more specific way. However, this conservation of general pattern does not reflect the evolution of gene specific pattern. Indeed, we show that nucleosome pattern diverged rapidly leaving practically no similarities between S. cerevisiae and C. glabrata orthologs. This was confirmed by different analysis and additional data from other species. In contrast, the pattern of gene expression and the response to stress were largely conserved among this species. Together, these results suggest that the general properties of nucleosome patterns and some specific features are conserved even if the gene specific patterns diverge much faster than the DNA sequence and the expression patterns. This argues strongly in favor of a model where different configurations of nucleosomes positions can encode the same expression output and where nucleosomes features evolve mainly by neutral drift

2010

Structural and functional analysis of host attachment proteins from contractile injection systems

Michel Plattner

Bacteriophages of the myoviridae family, R-type pyocin, Photorhabus virulence cassette (PVC), Serratia antifeeding prophage (Afp) and type 6 secretion system (T6SS) form a class of contractile injection systems that share common structural and functional components. The baseplate is a complex macromolecular structure that can change conformation. The tail is a rigid tube surrounded by a contractile sheath. They efficiently translocate genetic material (bacteriophages), deliver toxins into the external milieu or neighboring cells (PVC, Afp and T6SS) and efficiently kill competitor bacteria by depolarizing the membrane potential (Pyocin). The host range of bacteriophages or target spectrum of R-type pyocins, PVC, Afps is determined by filamentous tail fibers and more bulky tailspikes (TSP) that emanate from the baseplate. The recently discovered bacteriophage CBA120 encodes six putative host attachment proteins, of which four (named TSP1- TSP4) show some sequence similarity to known tailspikes. Despite four different proteins, CBA120 was found to be highly specific toward one host, namely E. coli O157:H7, a frequent contaminant of ground beef and a well-known human pathogen. In this work the crystallographic structure of TSP2, TSP3 and TSP4 are presented. In addition, functional assays suggest that CBA120 has at least three potential hosts. The structure of TSP1 was solved elsewhere but no activity was found towards E. coli O157:H7 or any other host. To better understand how the four TSP bind the phage particle, the TSP complex was formed in vitro and a new complex formation pathway was suggested. In addition to the CBA120, crystal structures of two TSP from Acinetobacter baumannii specific phages were solved. Acinetobacter baumannii is a highly drug resistant âflesh-eatingâ bacterium. Studies conducted with R-type pyocin show that its host specificity can be manipulated by changing the host attachment fiber. It was also shown that the native fiber protein could be exchanged for TSP proteins. In order to be incorporated in the pyocin particle, a new TSP can be fused to a 164 residue long N-terminal domain of the native fiber. This fragment is critical for maintaining the integrity of the baseplate and for transmitting the target surface binding signal to it. To obtain the structure of this fragment, we created a fusion of this domain with a well-crystallizable TSP. Several other proteins of the pyocin baseplate were cloned, expressed and purified. The result of these experiments was the determination of the crystal structure of the proteolytically stable fragment of PA0618, the largest protein of the pyocin baseplate. PA0618 is orthologous to T4 gp6, which is responsible of circularization of the baseplate. Taken together the structures of five previously unknown TSP and the proteolytically stable fragment of PA0618 were determined. The acquired structural information will help to better understand the relationship of peptide sequence, structure and function, in particular, the interaction of TSP and fiber proteins with polysaccharides that decorate the bacterial surface. Furthermore, all crystal structures reported here were determined by de novo phasing, and this structural information will further improve the ability to predict protein structure. Thanks to the enzymatic activity of the TSP proteins and their ability to specifically target bacterial cells, these proteins can be used in antimicrobial applications.

EPFL2018

Structural and functional analysis of host attachment proteins from contractile injection systems

Michel Plattner

EPFL2018