Case Study: Unraveling the Role of 3D Genome Rewiring in Human Accelerated Regions (HARs)

This case study highlights research into human accelerated regions (HARs) and their potential implications for human evolution. The study, by an international team of researchers led by Kathleen C. Keough, Ph.D., and colleagues at the Gladstone Institutes, was published in Science in 2023.

What are HARs and Why are They Important?

Some regions of the genome have evolved more quickly in humans than comparable genomic regions in other species. These regions – HARs – are believed to explain traits unique to humans, including aspects of our species’ neurodevelopment. This study leveraged Arima Genomics’ Hi-C technology to better understand the influence of structural variation found in HARs on 3D chromatin interactions, and gene regulatory networks.

Research Methodology and Key Findings

The researchers leveraged datasets from the Zoonomia Consortium alongside Arima Hi-C data to compare genomes from 241 mammals. By studying several data types including single-cell RNA-seq data, ATAC-seq data, and gene expression data, alongside insights from deep learning models, they predicted enhancer activity and validated structural changes observed in 3D chromatin folding in HARs.

These data helped the researchers identify genes found in HARs that were differentially expressed between humans and other mammalian species, and more specifically enabled identification of HAR-associated structural changes correlated with species-specific gene expression patterns present during neurodevelopment.

The Advantages of Arima Hi-C Technology in Evolutionary Biology Research

Arima Hi-C technology facilitates mapping 3D genome interactions at unprecedented resolution which helped Dr. Keough and her colleagues uncover relationships between structural changes and HAR function by connecting structural variations to regulatory network rewiring and differential gene expression.

Studying Hi-C data to understand 3D chromatin interactions alongside other multiomics data can help elucidate dynamic regulatory mechanisms critical to human evolution, as well as other human and mammalian biological processes.

To learn more about this research and to understand how Arima Hi-C technology can help answer your evolutionary biology questions, please download the full case study here.

Download the Case Study Here