Comparative 3D genome architecture in vertebrates

Abstract

Background The three-dimensional (3D) architecture of the genome has a highly ordered and hierarchical nature, which influences the regulation of essential nuclear processes at the basis of gene expression, such as gene transcription. While the hierarchical organization of heterochromatin and euchromatin can underlie differences in gene expression that determine evolutionary differences among species, the way 3D genome architecture is affected by evolutionary forces within major lineages remains unclear. Here, we report a comprehensive comparison of 3D genomes, using high resolution Hi-C data in fibroblast cells of fish, chickens, and 10 mammalian species. Results This analysis shows a correlation between genome size and chromosome length that affects chromosome territory (CT) organization in the upper hierarchy of genome architecture, whereas lower hierarchical features, including local transcriptional availability of DNA, are selected through the evolution of vertebrates. Furthermore, conservation of topologically associating domains (TADs) appears strongly associated with the modularity of expression profiles across species. Additionally, LINE and SINE transposable elements likely contribute to heterochromatin and euchromatin organization, respectively, during the evolution of genome architecture. Conclusions Our analysis uncovers organizational features that appear to determine the conservation and transcriptional regulation of functional genes across species. These findings can guide ongoing investigations of genome evolution by extending our understanding of the mechanisms shaping genome architecture.

TAD border deletion at theKitlocus causes tissue-specific ectopic activation of a neighboring gene

“…To estimate the evolutionary conservativity of TADs in the Kit locus, we liftovered Hi-C contacts from several vertebrate species to the mouse genome, using C-InterSecture software 21 , since a direct comparison of Hi-C maps from different species is inaccurate due to different genome sizes (Supplementary Fig.1a). Resulting interaction maps demonstrate a high similarity of chromosome architecture across the Kit locus in human, mice, dog, chicken 22 and african clawed frog 23 (Supplementary Fig.1b).…”

“…1a). Resulting interaction maps demonstrate a high similarity of chromosome architecture across the Kit locus in human, mice, dog, chicken 22 and african clawed frog 23 (Supplementary Fig. 1b).…”

Evolutionary analysis of gene ages across TADs associates chromatin topology with whole genome duplications

“…Early replicating TADs are expected to have more efficient DNA repair (Gaboriaud and Wu 2019) to reduce the probability of having damaging mutations; the low frequency of young genes in these TADs there might be a secondary effect of a lower mutation rate in these regions. Future availability of TADs in a wider diversity of species will allow to investigate the conservation of these TADs and their chromatin interactions (Álvarez-González et al, 2022; Li et al, 2022).…”

A Chromosome-Length Assembly of the Hawaiian Monk Seal (Neomonachus schauinslandi): A History of “Genetic Purging” and Genomic Stability

“…In addition, comparing sequence differences from healthy individuals of different species can be useful in distinguishing benign versus deleterious variants [ 4 ]. Chromosomal level assemblies are also necessary to establish blocks of synteny that may reflect both the evolutionary history of groups, e.g., [ 5 ], and help understand the importance of genome architecture in determining phenotypes, e.g., [ 6 , 7 ].…”