Spacing between conserved noncoding elements in the genome

• Applicant: Dr. Leila Taher
• Subject Area: Bioinformatics and Theoretical Biology ; General Genetics and Functional Genome Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565464303

- Wider research context / theoretical framework.Evolutionary conservation has historically been considered a hallmark of biological function. About 10% of the human genome exhibits strong sequence conservation with other mammals. While 1-2% of these conserved sequences encode proteins, many of the rest –commonly referred to as "conserved non-coding elements” (CNEs)– play crucial roles in gene regulation, for example, dictating when and where specific genes are expressed. Recent research, including our own findings, has shown that also the genomic distances (“spacing”) between pairs of adjacent CNEs is highly conserved despite sequence divergence. This suggests that the relative positioning of these CNEs, beyond just their individual sequences, is under selective pressure, opening up new avenues to explore the interplay between genome architecture and gene regulation. - Hypotheses / research questions / objectives. The general aim of this project is to further characterize the vertebrate noncoding genome and the evolutionary constraints acting on it. The project proposes that: 1. CNEs occurring in clusters and CNEs occurring in isolation are associated with distinct sequence and functional properties; 2. CNE spacing is under evolutionary pressure disregarding of whether CNEs occur in clusters or in isolation; and 3. Precise CNE spacing contributes to the establishment of higher-order genome structures, such as topologically associating domains. - Approach / methods. We will apply comparative genomics and phylogenetic inference to characterize the conservation of the spacing between CNEs with regards to that of the locus in which they are located, and clustering algorithms to classify the CNEs into different groups of genomic organizations. Further, we will use publicly available genomic and epigenomic data to understand the relationship between space conservation and regulatory and structural function of the involved CNEs. - Level of originality / innovation. None of the current models for regulatory sequences appear sufficient to explain the strong conservation exhibited by many CNEs. The present project proposes to shed light on the nature of the selection pressure to which CNEs are subjected from a new perspective, by investigating spatial constraints on the genomic organization of CNEs and the role of CNE genomic organization in regulatory function and in the establishment and maintenance of the three-dimensional structure of the genome.

• DFG Programme: Research Grants