Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and disease
Fleck, K.; Luria, V.; Garag, N.; Karger, A.; Hunter, T.; Marten, D.; Phu, W.; Nam, K.-M.; Sestan, N.; O'Donnell-Luria, A. H.; Erceg, J.
Show abstract
Genome organization is intricately tied to regulating genes and associated cell fate decisions. Here, we examine the positioning and functional significance of human genes, grouped by their lineage restriction level, within the 3D organization of the genome. We reveal that genes of different lineage restriction levels have distinct positioning relationships with both domains and loop anchors, and remarkably consistent relationships with boundaries across cell types. While the functional associations of each group of genes are primarily cell type-specific, associations of conserved genes maintain greater stability across 3D genomic features and disease than recently evolved genes. Furthermore, the expression of these genes across various tissues follows an evolutionary progression, such that RNA levels increase from young lineage restricted genes to ancient genes present in most species. Thus, the distinct relationships of gene evolutionary age, function, and positioning within 3D genomic features contribute to tissue-specific gene regulation in development and disease.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- TAD Evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function 97%
- The molecular basis, genetic control and pleiotropic effects of local gene co-expression 96%
- Transcription factor binding sites are frequently under accelerated evolution in primates 96%
Similar papers in this journal
- Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes 95%
- GeneWalk identifies relevant gene functions for a biological context using network representation learning 95%
- Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.