: PhD position (M/F) in comparative regulatory genomics: evolutionary origins of exonic enhancers

Job Description

Thesis Subject

Although cis-regulatory elements of gene expression are commonly assumed to lie outside of genes, there is extensive evidence that protein-coding exons can have regulatory functions (Lampe et al. 2008; Ritter et al. 2012; Birnbaum et al. 2012). Recent work has revealed that human and mouse genomes harbour thousands of protein-coding exons with strong transcription factor binding signals and enhancer-like chromatin signatures (Mouren et al. 2026). Subsequent assays for several hundreds of these elements validated their regulatory roles (Mouren et al. 2026). These findings call for a re-evaluation of regulatory element definition and of the functional impact of mutations that occur in protein-coding exons.

The doctoral research project funded under the ANR EXONHANCER program will address the evolutionary origins and trajectories of exonic enhancers, across vertebrate species. It aims to clarify how dual coding and regulatory constraints jointly shape the evolution of exonic enhancer sequences.

The PhD student will integrate genome annotations, whole-genome alignments to identify orthologous exonic enhancers and reconstruct their evolutionary histories. The project will investigate how protein-coding and regulatory constraints interact over long evolutionary timescales, and how more recent evolutionary forces shape exonic enhancers. The work will involve the development of reproducible bioinformatics workflows, statistical analyses and the visualization and interpretation of large-scale genomic datasets.

Candidates should hold, or expect to obtain before the start of the position, a Master's degree or equivalent in bioinformatics, computational biology, genomics, evolutionary biology or a related discipline. Essential skills include experience with genomic data analysis, proficiency in Python and/or R, familiarity with the Linux/Unix command line, and a solid foundation in statistics. Candidates should be able to work both independently and collaboratively and to communicate scientific results effectively in English.

Experience in comparative genomics, molecular evolution, phylogenetics, population genomics or transcriptomics would be an advantage. Familiarity with genomic data formats, high-performance computing, workflow managers such as Snakemake or Nextflow, and version control with Git would also be valuable, but prior experience in all these areas is not expected.

Your Work Environment

The PhD student will be based at the Laboratory for Biometry and Evolutionary Biology (LBBE) in Lyon, France (https://lbbe.univ-lyon1.fr/en).
The LBBE comprises approximately 200 people; the research conducted there is based on three pillars: (i) biometrics, with methodological developments in statistics, computer science, and mathematics for modeling living organisms; (ii) ecology and evolution, studied from the molecular and genomic levels to the levels of populations and communities; (iii) health, through the development of precision medicine and evidence-based medicine.

The project will be supervised by Anamaria Necsulea (LBBE, Lyon) and Benoît Ballester (TAGC, Marseille). The student will benefit from the complementary expertise of the LBBE in evolutionary and comparative genomics and of the TAGC in regulatory genomics and large-scale functional genomics.
Occasional travel (in France or abroad) to attend conferences or consortium meetings is to be expected. The candidate will be required to comply with the laboratory's internal regulations regarding all health and safety rules. The proposed work is entirel computational.


Advantages of working at the LBBE and at the CNRS:
- a stimulating and professional work environment, including access to internal training sessions within the host laboratory
- the possibility to work remotely
- access to an internal restaurant offering attractive prices for lunch
- partial reimbursement of public transportation fees (75%), including a sustainable transport stipend amounting to up to 300 euros/year
- working in a location that is accessible by public transport (tramways T1, T4, buses)
- 44 vacation days a year
- complementary social protection contract
Bibliography
Birnbaum, Ramon Y., E. Josephine Clowney, Orly Agamy, et al. 2012. “Coding Exons Function as Tissue-Specific Enhancers of Nearby Genes.” Genome Research 22 (6): 1059–68. https://doi.org/10.1101/gr.133546.111.
Lampe, Xavier, Omar Abdel Samad, Allan Guiguen, et al. 2008. “An Ultraconserved Hox-Pbx Responsive Element Resides in the Coding Sequence of Hoxa2 and Is Active in Rhombomere 4.” Nucleic Acids Research 36 (10): 3214–25. https://doi.org/10.1093/nar/gkn148.
Mouren, Jean-Christophe, Magali Torres, Antoinette van Ouwerkerk, et al. 2026. “Exonic Enhancers Are a Widespread Class of Dual-Function Regulatory Elements.” Nature Communications 17 (1): 4755. https://doi.org/10.1038/s41467-026-71220-6.
Ritter, Deborah I., Zhiqiang Dong, Su Guo, and Jeffrey H. Chuang. 2012. “Transcriptional Enhancers in Protein-Coding Exons of Vertebrate Developmental Genes.” PloS One 7 (5): e35202. https://doi.org/10.1371/journal.pone.0035202.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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