“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

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 and co-led a project that conducted 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 complex genomic variation

To fully understand human evolution, comparative approaches across the great apes—human, chimpanzee, gorilla, and orangutan—are necessary. Complex structural variation has played a relevant role in primate evolution, but has remained an understudied source of species divergence due to challenges with short-read genome sequencing technologies. By leveraging long-read sequencing technologies, I have comprehensively identified novel complex genetic variations in chimpanzee individuals and characterized a gene implicated in local adaptation to malaria in wild chimpanzee populations.

  • 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. bioRxiv. 2024. p. 2024.07.09.601734. doi:10.1101/2024.07.09.601734

(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.