Hyeonsoo "Harris" Jeong

I am a geneticist and computational scientist studying how gene regulation affects disease risk. My research focuses on an interesting aspect of genetics: gene expression can be altered without any changes to the actual DNA sequence itself. This can happen through epigenetic modifications, which are like molecular switches that turn genes on or off. I’m particularly interested in DNA methylation, one of the most important of these modifications, and how it affects genome function.

What makes this work interesting is that these epigenetic changes can help explain disease susceptability within human populations (e.g., why some people develop certain diseases while others don’t, even when they have similar genetic backgrounds?). During my Ph.D. with Soojin Yi at UCSB, I studied epigenomic changes between human and non-human primates. This comparative approach reveals the molecular changes that occurred during human evolution.

Building on this foundation, my postdoctoral work in Evan Eichler’s lab at the University of Washington took a deeper dive into human brain evolution. I investigated how these human-specific epigenomic regions have contributed to the unique aspects of neurodevelopment that distinguish our species. This involved generating complete telomere-to-telomere genome assemblies from both human and great ape induced pluripotent stem cells, then integrating multi-omics data from various differentiated cell types to understand how these genetic differences play out in actual brain development.

Since joining Altos, I’ve been working to bridge the gap between evolutionary biology and human health. By understanding how our evolutionary past shaped our genomes, we can better predict and potentially address disease susceptibility patterns that affect us during human evolution.

selected publications

PopGen
Structural polymorphism and diversity of human segmental duplications

Hyeonsoo Jeong^*, Philip C Dishuck^*, DongAhn Yoo^*, William T Harvey, and 10 more authors

Nature genetics, 2025

Abs DOI Bib

Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.2 Mb of duplicated sequence (47.4 Mb not present in the telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. We find that intrachromosomal SDs are among the most variable, with rare events mapping near their progenitor sequences. African genomes harbor significantly more intrachromosomal SDs and are more likely to have recently duplicated gene families with higher copy numbers than non-African samples. Comparison to a resource of 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding to these copy number polymorphic SDs.
@article{jeong2025structural, title = {Structural polymorphism and diversity of human segmental duplications}, author = {Jeong, Hyeonsoo and Dishuck, Philip C and Yoo, DongAhn and Harvey, William T and Munson, Katherine M and Lewis, Alexandra P and Kordosky, Jennifer and Garcia, Gage H and (HGSVC), Human Genome Structural Variation Consortium and Yilmaz, Feyza and Hallast, Pille and Lee, Charles and Pastinen, Tomi and Eichler, Evan E.}, journal = {Nature genetics}, volume = {57}, number = {2}, pages = {390--401}, year = {2025}, dimensions = {true}, doi = {10.1038/s41588-024-02051-8}, pubmed = {39779957}, publisher = {Nature Publishing Group US New York} }
Evolution
Evolution of DNA methylation in the human brain

Hyeonsoo Jeong^*, Isabel Mendizabal^*, Stefano Berto, Paramita Chatterjee, and 9 more authors

Nature communications, 2021

Abs DOI Bib

DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.
@article{jeong2021evolution, title = {Evolution of DNA methylation in the human brain}, author = {Jeong, Hyeonsoo and Mendizabal, Isabel and Berto, Stefano and Chatterjee, Paramita and Layman, Thomas and Usui, Noriyoshi and Toriumi, Kazuya and Douglas, Connor and Singh, Devika and Huh, Iksoo and Preuss, Todd M. and Konopka, Genevieve and Yi, Soojin V.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2021}, year = {2021}, doi = {10.1038/s41467-021-21917-7}, url = {https://www.nature.com/articles/s41467-021-21917-7}, dimensions = {true}, publisher = {Nature Publishing Group UK London} }

PopGen

Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows

Hyeonsoo Jeong^*, Nicole M Baran^*, Dan Sun, Paramita Chatterjee, and 4 more authors

Elife, 2022

DOI Bib

@article{jeong2022dynamic,
  title = {Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows},
  author = {Jeong, Hyeonsoo and Baran, Nicole M and Sun, Dan and Chatterjee, Paramita and Layman, Thomas S and Balakrishnan, Christopher N and Maney, Donna L and Yi, Soojin V},
  journal = {Elife},
  volume = {11},
  pages = {e79387},
  year = {2022},
  dimensions = {true},
  doi = {10.7554/elife.79387},
  publisher = {eLife Sciences Publications Limited}
}

Evolution

Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation

Hyeonsoo Jeong, Bushra Arif, Gustavo Caetano-Anollés, Kyung Mo Kim, and 1 more author

Scientific reports, 2019

DOI Bib

@article{jeong2019horizontal,
  title = {Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation},
  author = {Jeong, Hyeonsoo and Arif, Bushra and Caetano-Anoll{\'e}s, Gustavo and Kim, Kyung Mo and Nasir, Arshan},
  journal = {Scientific reports},
  volume = {9},
  number = {1},
  pages = {5953},
  year = {2019},
  dimensions = {true},
  doi = {10.1038/s41598-019-42227-5},
  publisher = {Nature Publishing Group UK London}
}

Evolution

HGTree: database of horizontally transferred genes determined by tree reconciliation

Hyeonsoo Jeong, Samsun Sung, Taehyung Kwon, Minseok Seo, and 5 more authors

Nucleic acids research, 2016

DOI Bib

@article{jeong2016hgtree,
  title = {HGTree: database of horizontally transferred genes determined by tree reconciliation},
  author = {Jeong, Hyeonsoo and Sung, Samsun and Kwon, Taehyung and Seo, Minseok and Caetano-Anoll{\'e}s, Kelsey and Choi, Sang Ho and Cho, Seoae and Nasir, Arshan and Kim, Heebal},
  journal = {Nucleic acids research},
  volume = {44},
  number = {D1},
  pages = {D610--D619},
  year = {2016},
  dimensions = {true},
  doi = {10.1093/nar/gkv1245},
  publisher = {Oxford University Press}
}