Skip to main content

Regulation and Variability of Animal Genome Expression

Final Activity Report Summary - RIVAGE (Regulation and Variability of Animal Genome Expression)

The ‘Regulation and variability of animal genome expression’ (RIVAGE) was a Marie Curie early stage research training action (MEST-CT-2004-504854), with training taking place at the ‘National Institute for Agronomical research’ (INRA) Jouy-en-Josas research centre. The project aimed to develop integrative biology in livestock animals and consisted by a network of animal geneticist and physiologists addressing two main questions:

1. what was the link between genetic variability and genetic expression
2. which factors drove gene expression.

The work plan included 13 specific and interdisciplinary projects, lasting 12 to 36 months, which were led by early researchers coming from six European and three third countries, dedicated to a better understanding of

1. resistance to disease and defence and
2. cell growth and differentiation.

RIVAGE was a training programme based on five doctoral training modules recognised by three regional graduate schools, evolving through taking into account the most recent results obtained by RIVAGE network. RIVAGE was a methodology for the progressive creation of a dynamic and recognised interdisciplinary science, based on training by and through research. Moreover, RIVAGE was an attempt to think training differently by research in the European research area, through initiatives to develop interdisciplinary science and support career of early stage researchers taking part in the process.

Using dedicated animal models, such as ascidian, fish, chicken, goat, sheep and bovine, specific genetic models, e.g. selected breeds, mutants, transgenic and clonal lines, and up-to-date tools, namely sequence data bases, transcriptomic, proteomic and image analysis, we were able to draw a more complex and integrated picture of the relationship between the genotype and the phenotype. What was the link between genetic variability and genetic expression? All the results obtained within the project by the time of its completion illustrated that we could still not infer the phenotype from the genotype, even when the genetic determinism was known or controlled, like in mutant or selected lines, and whatever being the complexity of the trait considered. With marked genotypes, like mutants, or when working with individuals harbouring the same genotype, i.e. clones, we were able to get the transcriptomic signature of specific phenotypes, which helped us to decipher a specific function. We also showed that even a single polymorphism could cause significant alteration of cascades of genes expression.

Then, what drove gene expression? When we merged what we knew about gene structure and the regulatory sequences, we were sometimes able to control gene expression, but not always. Gene structure and genome structure were other drivers of gene expression. The expression of a specific gene could be affected by its position in the genome, due to the variable attachment of the gene to the matrix of the genome. We highlighted the direct role of genome organisation on the regulation of genome expression. We also pointed out an additional level of gene expression regulation outside of the genome, which could be autonomous and linked to the metabolic status of the cell. Altogether, our results showed that the molecular connection between genetic variability and phenotypic variability was explained by variations in regulatory sequences, in gene structure, in genome organisation as well as by autonomous regulations of gene cascades and networks.

In order to produce such knowledge the RIVAGE network was able to go beyond the classical technical exchanges between experts of different disciplines and produce a sounded interdisciplinary science, which every researcher would know and split around Europe. The method used to develop such interdisciplinary science was based on four principles:

1. work on a solid and evolving disciplinary background
2. ensure the permanent and progressive opening out to multidiscipline
3. consider the evolution of the career at each step
4. provide means to promote the recognition of the knowledge and future careers raised by interdisciplinary science.

The next step was to build an interdisciplinary network that also merged mathematicians. RIVAGE was, by the time of the project completion, an incubator of such a novel training project.