Abstract
Conserved non-coding elements (CNEs) in the mammalian have long been associated with cis-regulatory activity. The general aim of this project is to further characterize the CNEs in the mammalian genome and the evolutionary constraints acting on them. We hypothesize that CNEs occurring in clusters have distinct functional and sequence properties than isolated CNEs.
To evaluate the evolutionary pressure acting on the genomic distance between neighboring CNEs, we first identified about 1.2 million CNEs in the human genome. The majority of these CNEs were placed in intronic (54%) areas, then intergenic (44%), and a minority in UTRs (2%). Next, we separated CNEs into two groups: almost all CNEs were found in ~30,000 clusters (two or more CNEs with no conserved coding elements (CCE) in between them, with an average of 40 CNEs), and only ~8,000 were found as isolated CNEs. We then used multiple genome alignment of 100 vertebrates and phylogenetic analysis to infer the genomic distance between pairs of CNE within clusters as well as between their nearest upstream and downstream CCEs. For Tetrapoda, we observed that the distance between the CCEs tends to be conserved, while the distance between CNEs has contracted in humans with respect to the last common ancestor. This suggests that not only the conservation of a non-coding element itself, but also the conservation of the distance between CNEs might be associated with function, which would support our hypothesis. Furthermore, CNE pairs with contracted and conserved distances exhibited lower transposon densities compared to random genomic regions, suggesting that differences in genomic distances were driven by transposon activity.
The investigation of clusters of conserved non-coding elements (CNEs) is expected to provide insights into the mechanisms of gene regulation and our understanding of human disease.
To evaluate the evolutionary pressure acting on the genomic distance between neighboring CNEs, we first identified about 1.2 million CNEs in the human genome. The majority of these CNEs were placed in intronic (54%) areas, then intergenic (44%), and a minority in UTRs (2%). Next, we separated CNEs into two groups: almost all CNEs were found in ~30,000 clusters (two or more CNEs with no conserved coding elements (CCE) in between them, with an average of 40 CNEs), and only ~8,000 were found as isolated CNEs. We then used multiple genome alignment of 100 vertebrates and phylogenetic analysis to infer the genomic distance between pairs of CNE within clusters as well as between their nearest upstream and downstream CCEs. For Tetrapoda, we observed that the distance between the CCEs tends to be conserved, while the distance between CNEs has contracted in humans with respect to the last common ancestor. This suggests that not only the conservation of a non-coding element itself, but also the conservation of the distance between CNEs might be associated with function, which would support our hypothesis. Furthermore, CNE pairs with contracted and conserved distances exhibited lower transposon densities compared to random genomic regions, suggesting that differences in genomic distances were driven by transposon activity.
The investigation of clusters of conserved non-coding elements (CNEs) is expected to provide insights into the mechanisms of gene regulation and our understanding of human disease.
| Original language | English |
|---|---|
| Publication status | Published - 11 Oct 2023 |
| Event | 2023 EMBL Symposium The non-coding genome - EMBL, Heidelberg, Germany Duration: 11 Oct 2023 → 14 Oct 2023 https://www.embl.org/about/info/course-and-conference-office/events/ees23-10/ |
Conference
| Conference | 2023 EMBL Symposium The non-coding genome |
|---|---|
| Country/Territory | Germany |
| City | Heidelberg |
| Period | 11/10/23 → 14/10/23 |
| Internet address |
