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{"id":7726,"date":"2020-04-20T15:47:55","date_gmt":"2020-04-20T14:47:55","guid":{"rendered":"http:\/\/signalife.unice.fr\/?page_id=7726"},"modified":"2020-11-17T16:43:36","modified_gmt":"2020-11-17T15:43:36","slug":"2020-4","status":"publish","type":"page","link":"https:\/\/signalife.univ-cotedazur.fr\/?page_id=7726","title":{"rendered":"In the Spotlight 2020"},"content":{"rendered":"
\n2020 Labex Publication<\/strong><\/h2>\n
\u201cGene flow among reproductively isolated species\u201d<\/h4>\n
Dr Gianni Liti, a Labex SIGNALIFE project leader working on Population Genomics and Complex Traits, has just recently\u00a0published in Nature a paper on how genomic introgressions occur among reproductively isolated yeast species<\/p>\n
This publication involved Dr Liti\u2019s research team at the Institute for Research on Cancer and Aging Nice (IRCAN) at The\u00a0University C\u00f4te d\u2019Azur, among them one Labex PhD student,\u00a0Melania D\u2019Angiolo as first author\u00a0!!<\/strong><\/p>\n
D\u2019Angiolo M, De Chiara M, Yue JX, Irizar A, Stenberg S, Persson K, Llored A, Barr\u00e9 B, Schacherer J, Marangoni R, Gilson E, Warringer J and Liti G. 2020. A yeast living ancestor reveals the origin of genomic introgressions. Nature<\/strong>. In press.<\/p>\n
https:\/\/www.nature.com\/articles\/s41586-020-2889-1<\/a><\/p>\n
![\"\"](\"https:\/\/signalife.univ-cotedazur.fr\/wp-content\/uploads\/2020\/11\/publi-Gianni.jpg\")
<\/a><\/p>\nEnglish version<\/strong><\/p>\n
How can organisms whose DNA are so different that sex between them fails to create offspring, nevertheless exchange genes? This mystery has irked biologists for many years. We now disclose an unexpected mechanism that allows DNA exchange in absence of sex, helped by the lucky finding of a living yeast fossil with an ancient genome structure.<\/p>\n
Lineages that become separated from each other, for example by migration, accumulate unique differences in their DNA, which are due to errors that occur when they copy their DNA. Lineages that encounter each other after having spent substantial time apart can nevertheless often engage in sex and produce hybrids with mixed DNA. Offspring from these hybrids, as they can find no other mates, typically cross back to one of the parent lineages, and beget children whose DNA is predominantly of one of the DNA types. After many generations of such backcrossings, only short scattered segments of the other DNA type, known as introgressions, remain. Non-African human populations carry 2% of Neanderthal DNA, as a result of ancient admixture and introgression. DNA introgressed from one species into another can have both positive and negative effects and these change over time. Some genes introgressed from Neanderthals have recently become a threat to human health as they increase the risk of COVID-19.<\/p>\n
Mysteriously, we often find gene introgressions between species whose DNA are so different that sex fails to produce offspring. How is this possible? Evidently, the reproductive barriers have been penetrated, but how has long remained a conundrum. Common baker\u2019s yeast, humans\u2019 best friend that help us produce bread, beer, wine, spirits, coffee, cacao and many other products that are important to human wellbeing, is reproductively isolated from its wild sister species, the otherwise insipid Saccharomyces paradoxus<\/em>. While the two yeasts can mate and form hybrids, their DNA differences (~12%) prevent them from exchanging DNA correctly and their offspring almost always die. Nevertheless, stretches of S. paradoxus<\/em> DNA have invaded baker\u2019s yeast genomes in a process resembling the introgression of Neanderthal DNA into non-African humans. How could these yeast DNA introgressions occur when the hybrid is sterile?<\/p>\n
We stumbled across a clone of an ancestral yeast hybrid with a genome structure that is hundreds of thousands of generations old, i.e. a real living fossil. Curiously, the two genome copies in this living fossil had become identical at many places, where the S. paradoxus<\/em> DNA had been copied onto, and thereby replaced, the baker\u2019s yeast DNA. Even more surprisingly, we found that this living fossil was the direct ancestor of a modern-day baker\u2019s yeast population, the Alpechin yeasts, that today live in the waste-water from olive presses and carry stretches of introgressed S. paradoxus<\/em> DNA. Irked by this seeming coincidence, we compared the places where the living fossil carried identical DNA in its two genomes to the places where S. paradoxus<\/em> DNA had introgressed in Alpechin yeasts \u2013 and found them to be the same. In other words: the scattered blocks of identical DNA in the living fossil had given rise to the introgressions in its modern descendants. Further experiments shed light on how this had occurred: the scattered blocks of identical DNA allow the living fossil to pair its two genomes and mix their DNA such that the sexual reproduction barrier is overcome and viable offspring produced. The children in turn can mate back to the baker\u2019s yeast, giving rise to grandchildren that carry long stretches of introgressed S. paradoxus<\/em> DNA. Continuing this process produces genomes that very much look like those of the Alpechin yeasts. This discovery solved the long-standing mystery of how reproductively isolated species can exchange DNA: the secret is simply blocks of identical DNA that allow their two genomes to pair and mix. How do such scattered blocks of identical DNA emerge? Well, that is another mystery waiting for its resolution.<\/p>\n
French version:<\/strong><\/p>\n
Comment des organismes sexuellement incompatibles peuvent-ils \u00e9changer du mat\u00e9riel g\u00e9n\u00e9tique\u00a0? Ce myst\u00e8re suscite l\u2019int\u00e9r\u00eat de la communaut\u00e9 scientifique depuis de nombreuses ann\u00e9es. Gr\u00e2ce \u00e0 la d\u00e9couverte d\u2019une souche de levure \u00e0 l\u2019architecture g\u00e9n\u00e9tique ancestrale, nous avons pu mettre en \u00e9vidence un nouveau m\u00e9canisme permettant l\u2019\u00e9change de mat\u00e9riel g\u00e9n\u00e9tique sans avoir recours \u00e0 la reproduction sexu\u00e9e.<\/p>\n
Lorsque des groupes d\u2019individus sont s\u00e9par\u00e9s les uns des autres, ils accumulent progressivement dans leur g\u00e9nome des mutations propres \u00e0 chaque groupe, dues \u00e0 des erreurs lors de la r\u00e9plication de l\u2019ADN. Plus tard, si ces individus issus de groupes distincts se rencontrent, ils peuvent n\u00e9anmoins se reproduire sexuellement et donner naissance \u00e0 un hybride, constitu\u00e9 pour moiti\u00e9 de chaque ADN parental. Il arrive que ces hybrides se reproduisent avec des individus provenant d\u2019un des deux groupes originels, engendrant ainsi des descendants dont le g\u00e9nome est enrichi seulement avec l\u2019un des ADN parentaux. Apr\u00e8s plusieurs g\u00e9n\u00e9rations de r\u00e9trocroisements de ce type, seuls de rares fragments d\u2019ADN issus de l\u2019autre parent originel persistent\u00a0; ces fragments sont appel\u00e9s introgressions. Par exemple, 2% du g\u00e9nome humain d\u2019origine non-Africaine contient de l\u2019ADN de N\u00e9andertal r\u00e9sultant de ce processus d\u2019introgression. Les introgressions d\u2019ADN peuvent aussi bien avoir des effets positifs que n\u00e9gatifs, et \u00e9voluer au cours du temps. Il a d\u2019ailleurs r\u00e9cemment \u00e9t\u00e9 constat\u00e9 que certains g\u00e8nes directement h\u00e9rit\u00e9s de N\u00e9andertal augmentent significativement la sensibilit\u00e9 au COVID-19, mena\u00e7ant la sant\u00e9 humaine.<\/p>\n
Myst\u00e9rieusement, nous observons souvent des introgressions chez des esp\u00e8ces g\u00e9n\u00e9tiquement \u00e9loign\u00e9es qui ne peuvent se reproduire sexuellement l\u2019une avec l\u2019autre. Ce ph\u00e9nom\u00e8ne est longtemps rest\u00e9 une \u00e9nigme. La levure du boulanger Saccharomyces cerevisiae<\/em>, champignon unicellulaire indispensable \u00e0 la production de pain, de bi\u00e8re, de vin, de spiritueux, de caf\u00e9, ou encore de cacao pour ne citer que quelques exemples, est reproductivement isol\u00e9e de son esp\u00e8re s\u0153ur Saccharomyces paradoxus<\/em>. Malgr\u00e9 le fait que ces deux esp\u00e8ces de levures peuvent s\u2019accoupler et former des hybrides, leur forte divergence g\u00e9n\u00e9tique (~12%) rend leur descendance majoritairement non-viable, limitant ainsi l\u2019\u00e9change de mat\u00e9riel g\u00e9n\u00e9tique. Cependant, des fragments d\u2019ADN de S. paradoxus<\/em> ont \u00e9t\u00e9 retrouv\u00e9s dans le g\u00e9nome de S. cerevisiae<\/em>, selon un processus vraisemblablement similaire aux introgressions de N\u00e9andertal observ\u00e9es chez l\u2019humain. Comment cela est-il possible alors que les hybrides de S. cerevisiae<\/em> et S. paradoxus<\/em> sont st\u00e9riles\u00a0?<\/p>\n
Nous avons isol\u00e9 une souche hybride ancestrale de levure dont la structure g\u00e9nomique n\u2019a pas \u00e9volu\u00e9 depuis des centaines de milliers de g\u00e9n\u00e9rations, telle un v\u00e9ritable fossile vivant. Curieusement, les chromosomes homologues de cette levure fossile sont parfaitement identiques en plusieurs endroits o\u00f9 l\u2019ADN de S. paradoxus<\/em> a compl\u00e8tement remplac\u00e9 celui de S. cerevisiae<\/em>. De plus, nous avons d\u00e9montr\u00e9 que cette levure fossile est l\u2019anc\u00eatre direct d\u2019une autre souche moderne de S. cerevisiae <\/em>d\u00e9nomm\u00e9e Alpechin, trouv\u00e9e dans les eaux us\u00e9es de la production d\u2019huile d\u2019olive et pourvue d\u2019introgressions de S. paradoxus<\/em>. Suite \u00e0 ce constat, nous avons compar\u00e9 les emplacements o\u00f9 l\u2019ADN de S. paradoxus<\/em> a compl\u00e8tement remplac\u00e9 celui de S. cerevisiae<\/em> chez la levure fossile, avec les zones d\u2019introgressions chez Alpechin, et nous avons constat\u00e9 qu\u2019elles co\u00efncidaient. En fait, les introgressions de S. paradoxus <\/em>dans les levures Alpechin r\u00e9sultent directement des fragments maintenus dans la souche ancestrale. Des exp\u00e9riences plus approfondies nous ont permis d\u2019\u00e9claircir les faits\u00a0: les blocs d\u2019ADN de S. paradoxus<\/em> conserv\u00e9s dans les chromosomes homologues de la levure fossile lui permettent de recombiner plus efficacement son g\u00e9nome lors de la formation de gam\u00e8tes pour la reproduction sexu\u00e9e. Les descendants de la levure fossile ont alors \u00e9t\u00e9 r\u00e9trocrois\u00e9s successivement avec S. cerevisiae<\/em> donnant ainsi naissance \u00e0 des descendants comportant de longs fragments d\u2019introgressions d\u2019ADN de S. paradoxus<\/em>. A terme, ce sc\u00e9nario aboutit \u00e0 la formation de g\u00e9nomes tr\u00e8s semblables \u00e0 celui des levures Alpechin.<\/p>\n
Cette d\u00e9couverte a ainsi permis d\u2019expliquer comment des esp\u00e8ces reproductivement isol\u00e9es peuvent \u00e9changer du mat\u00e9riel g\u00e9n\u00e9tique\u00a0: la formation de blocs d\u2019ADN identiques sur les deux chromosomes homologues permet aux g\u00e9nomes hybrides de se recombiner. Comment ces blocs se forment-ils\u00a0? Cela reste encore \u00e0 \u00e9lucider.<\/p>\n
<\/p>\n
2020 Research development<\/strong><\/span><\/h2>\n
\u00ab\u00a0Profiling the Non-genetic Origins of Cancer Drug Resistance\u00a0\u00bb<\/h4>\n
A group of researchers led by Dr J\u00e9r\u00e9mie Roux, member of the Labex SIGNALIFE team<\/strong> of Prof. Hofman<\/strong> at the Institute for Research on Cancer and Aging (IRCAN) has developed a new method to anticipate how cells respond to cancer treatment<\/p>\n
![\"\"](\"https:\/\/signalife.univ-cotedazur.fr\/wp-content\/uploads\/2020\/11\/20201011_Nice_matin_Roux-petit-1.jpg\")
<\/a><\/p>\nScientific publication link<\/p>\n
https:\/\/doi.org\/10.1016\/j.cels.2020.08.019<\/a><\/p>\n
Canceropole PACA Press release<\/p>\n
https:\/\/canceropole-paca.com\/wp-content\/uploads\/2020\/09\/CP-J.Roux-Cell-Systems-1.pdf<\/a><\/p>\n
Social networks<\/p>\n
https:\/\/twitter.com\/jrxlab\/status\/1310614614590324736<\/a><\/p>\n
https:\/\/twitter.com\/CanceropolePACA\/status\/1310862977776717824<\/a><\/p>\n
https:\/\/twitter.com\/CellSystemsCP\/status\/1318938091185295361<\/a><\/p>\n
https:\/\/twitter.com\/Nice_Matin\/status\/1315194191237058562<\/a><\/p>\n
<\/h2>\n
<\/p>\n
2020 Start up creation<\/strong><\/span><\/h2>\n
\u201cRegeneration of pancreatic insulin-producing cells\u201d<\/h4>\n
Dr Patrick Collombat, a Labex SIGNALIFE project leader working in Diabetes Genetics, has recently created a Startup on regeneration of pancreatic insulin-producing cells.<\/p>\n
The project involved his research team at the Institut de Biologie Valrose in The University C\u00f4te d\u2019Azur, among them 2 former Labex PhD students, Tiziana Napolitano and Serena Silvano<\/strong>. Tiziana is now employed by the Startup DiogenX<\/a><\/p>\n
![\"\"](\"https:\/\/signalife.univ-cotedazur.fr\/wp-content\/uploads\/2020\/09\/Article-Patrick.jpg\")
<\/a><\/p>\n<\/h2>\n
<\/h2>\n
2020 Labex Publication<\/strong><\/span><\/h2>\n
\u00ab\u00a0Novel immune surveillance mechanism of the skin compromised in Xeroderma Pigmentosum patients\u00a0\u00bb<\/h4>\n
Labex discoveries from a collaboration between V\u00e9ronique Braud\u2019s (IPMC) and Thierry Magnaldo\u2019s (IRCAN) teams including a PhD Student, Gon\u00e7alves-Maia Maria, supported by the Fondation Avenir and the Labex SIGNALIFE<\/strong><\/p>\n
Using an innovative 3-dimensional organotypic skin culture model that contain Natural Killer cells, fibroblasts and squamous cell carcinoma (SCC) cells, the teams unveiled a key role of CLEC2A, a molecule expressed by fibroblasts, and implicated in the activation of NK cells, leading to the control of SCC invasion. They discovered that this regulation is compromised in patients with Xeroderma Pigmentosum.<\/p>\n
Gon\u00e7alves-Maia M, Gache Y, Basante M, Cosson E, Salavagione E, Muller M, Bernerd F, Avril MF, Schaub S, Sarasin A, and VM Braud*<\/strong>, T Magnaldo* (*co-authorship). 2020. NK cell and fibroblast-mediated regulation of skin squamous cell carcinoma invasion by CLEC2A is compromised in Xeroderma Pigmentosum. J Invest Dermatol<\/em>.<\/strong> (IF-6.3) 13:S0022-202X(20)30142-1. PMID: 32061658<\/strong><\/p>\n
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