- “Anything becomes interesting if you look at it long enough.” ― Gustave Flaubert
- “Nearly everything is really interesting if you go into it deeply enough.” ― Richard Feynman
I study what makes the human brain unique by comparing it to the brains of non-human primates, uncovering genetic and epigenetic changes that shaped our evolution and may reveal why we’re vulnerable to neuropsychiatric disorders.
My research focuses on elucidating genetic and epigenetic changes contributing to human brain evolution and neuropsychiatric disease risk. To do so, I integrate human genetics with population, comparative, and functional genomic approches, across humans and non-human primates. My current research areas include:
(1) Genetic and epigenetic changes contributing to human brain evolution
Gene duplications are a key driver of evolutionary innovation. My doctoral and postdoctoral research centered on studying human-specific gene duplications, where I contributed to characterizing the epigenetic landscape and expression patterns of 75 duplicated genes across various human tissues. Then, I co-led a project conducting a comprehensive survey of recent human gene duplications, leveraging the first complete human genome. This work identified approximately 350 neurodevelopmental genes, highlighting two genes that increase brain size in zebrafish. Additionally, I contributed to characterizing a gene implicated as a human-specific modifier of neuronal excitability.
- Shew CJ, Carmona-Mora P, Soto DC, Mastoras M, Roberts E, Rosas J, et al. Diverse molecular mechanisms contribute to differential expression of human duplicated genes. Mol Biol Evol. 2021. doi:10.1093/molbev/msab131
- Soto DC†, Uribe-Salazar JM†, Kaya G, Valdarrago R, Sekar A, Haghani NK, et al. Gene expansions contributing to human brain evolution. bioRxiv. 2024. doi:10.1101/2024.09.26.615256
- Libé-Philippot B, Lejeune A, Wierda K, Louros N, Erkol E, Vlaeminck I, et al. LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons. Cell. 2023;186: 5766-5783.e25.
(2) Primate comparative genomics and epigenomics
To fully understand human evolution, comparative approaches across the great apes—human, chimpanzee, gorilla, and orangutan—and other non-human primates are essential. Complex structural variation, a key contributor to primate evolution, has remained an underexplored source of species divergence due to the limitations of short-read sequencing technologies. By harnessing long-read sequencing, I have comprehensively identified novel complex genetic variants in chimpanzees and characterized a gene involved in local malaria adaptation among wild chimpanzee populations. Beyond genetic variation, the evolution of gene regulation is a major factor in phenotypic differences among primates. My current work focuses on gene expression evolution, using comparative neurogenomic approaches across primates spanning ~30 million years of evolutionary history.
- Soto DC†, Uribe-Salazar JM†, Shew CJ†, Sekar A, McGinty SP, Dennis MY. Genomic structural variation: A complex but important driver of human evolution. Am J Biol Anthropol. 2023. doi:10.1002/ajpa.24713.
- Soto DC†, Shew CJ†, Mastoras M, Schmidt JM, Sahasrabudhe R, Kaya G, et al. Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing. Genes. 2020;11: 276.
- Ostridge HJ, Fontsere C, Lizano E, Soto DC, Schmidt JM, Saxena V, et al. Local genetic adaptation to habitat in wild chimpanzees. Science. 2025;387: eadn7954. doi:10.1126/science.adn7954
(3) The genetics of neuropsychiatric disorders
The evolution of the uniquely human brain has also given rise to neurodiversity, some of which contributes to neuropsychiatric and neurodevelopmental disorders. I have collaborated on several studies exploring the genetic basis of autism spectrum disorders and behavioral genetics, including the characterization of a structural variant associated with autism risk, the investigation of the epigenetic landscape of chromosome 15q11-q13 linked to Prader-Willi and Angelman syndromes, and the study of the genetics of behavior in rodents.
- Zhu Y, Gomez JA, Laufer BI, Mordaunt CE, Mouat JS, Soto DC, et al. Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism. Genome Biol. 2022;23: 1–32.
- Gutierrez Fugón OJ, Sharifi O, Heath N, Soto DC, Gomez JA, Yasui DH, et al. Integration of CTCF loops, methylome, and transcriptome in differentiating LUHMES as a model for imprinting dynamics of the 15q11-q13 locus in human neurons. Hum Mol Genet. 2024; ddae111.
- Chen PB, Chen R, LaPierre N, Chen Z, Mefford J, Marcus E, et al. Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior. Cell Genom. 2024; 100545.