Chromatin Structure and Human Genome Evolution


Large‐scale sequencing projects and comparative genomics have provided insights into the function and evolution of many fragments of the human genome, but relatively little is known about the spatial organisation of the genome. This is a major gap in our knowledge as the elaborate physical structure of the genome reflects the spatial and temporal organisation of nuclear processes. It has also long been suspected that the structural and functional organisation of the genome might impose constraints on its evolutionary history. Our emerging view of chromatin structure has already provided unexpected insights into human genome evolution, describing the impact of such constraints on the evolution of chromosome architecture, on gene function and on patterns of mutation and selection. The study of the transgenerational inheritance of chromatin variants, in parallel with the inheritance of deoxyribonucleic acid (DNA) sequence variants, promises to revolutionise our views of evolution and disease.

Key Concepts:

  • The physical structure of the genome, chromatin structure and nuclear organisation, is important for many aspects of genome function.

  • Chromatin structure can also influence the evolution of the genome.

  • Many aspects of chromatin structure are detectably conserved among mammals.

  • There is an interplay between chromatin structure and the patterns of divergence seen in the underlying DNA sequence.

  • This interplay can be seen at the level of individual genes and their regulatory elements, but also at the level of multimegabase domains of higher order chromatin structure.

Keywords: chromatin structure; epigenome; human genome; comparative genomics; evolution

Figure 1.

Conservation of higher‐order chromatin structure. (a) The dendrogram shows the relationships among human and mouse replication timing data in several embryonic stem cell (ESC) and neural progenitor cell (NPC) lines (Ryba et al., ; Hiratani et al., ), with species (human=pink, mouse=grey) and strength of correlation (0.65≤Spearman's Rho≤0.98, p‐value<2.2e−16) indicated in the heatmap. (b) Mean mouse ESC (Hiratani et al., ) and mean human ESC (Ryba et al., ) replication timing values (red and blue respectively) in 100 Kb windows over a representative 25 Mb region of human chromosome 1 and over the orthologous 100 Kb mouse genome regions.

Figure 2.

Higher‐order chromatin structure and histone modifications. The relationships between the densities of various histone modifications (Xiao et al., ) and replication timing data in human ESCs (Ryba et al., ). Replication timing and histone modification data is averaged over 100 Kb windows.



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Chambers, Emily V, and Semple, Colin AM(Jun 2013) Chromatin Structure and Human Genome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020999.pub2]