About

Ricardo Mallarino is an Associate Professor of Molecular Biology at Princeton University. Originally from Bogota, Colombia, he earned a B.S. in Biology from Universidad de los Andes and completed his Ph.D. in Biology at Harvard University in 2011, working with Arhat Abzhanov on developmental mechanisms underlying beak shape diversity in Darwin’s finches and their close relatives. His research focuses on understanding the genetic and developmental mechanisms by which form and structure are regulated during vertebrate embryogenesis and how these processes are modified during evolutionary time to produce phenotypic diversity. The Mallarino lab combines the study of emerging model organisms with traditional model species, employing approaches such as experimental embryology, transcriptomic and epigenomic profiling, comparative genomics, functional genetics, and imaging to uncover gene functions and mechanisms of evolutionary change. He has been recognized as a Vallee Scholar in 2021 and a Searle Scholar and Sloan Fellow in 2019.

Research topics

• Biology
• Evolutionary biology
• Genetics
• Zoology
• Ecology

Selected publications

• Agouti integrates environmental cues to regulate paternal behaviour

  Nature · 2026-02-18

  articleOpen access

  Paternal care is rare among mammals and the neural mechanisms governing its emergence are poorly understood1. We leveraged the natural paternal behaviour of African striped mice (Rhabdomys pumilio)2,3, and integrated brain-wide cFos mapping, single-nucleus RNA sequencing, virally mediated gene perturbation and environmental manipulation to dissect the neural basis of natural variation in male parenting. Here we find that socio-environmental conditions drive individual variation in male alloparenting such that postweaning social isolation increases paternal care whereas social living in higher density groups increases infanticide. This natural variation in care corresponds to neural activity in the medial preoptic area and changes in correlated activity across brain regions. Within the medial preoptic area, expression of agouti signalling protein (Agouti) in neurons is increased by group housing and is negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant mice. Naturalistic manipulations further reveal that Agouti integrates long-term housing conditions rather than food availability or hunger. Our findings reveal that variation in male paternal care reflects context-dependent regulation of conserved hypothalamic and melanocortin signalling mechanisms rather than the presence or absence of paternal capacity. Expression of agouti signalling protein in neurons in the medial preoptic area is increased by group housing and negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant mice.

  PublisherDOI

• <i>Agouti</i> integrates environmental information to regulate natural variation in paternal behavior

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-17 · 1 citations

  preprintOpen access

  ABSTRACT Male investment in offspring rearing through paternal care is rare among mammals and the neural mechanisms governing its emergence are poorly understood. We leveraged the natural paternal behavior of African striped mice ( Rhabdomys pumilio ) in combination with brain-wide cFos quantification, single-nucleus RNA-sequencing, viral-mediated gene manipulation, and environmental manipulation to dissect the neural basis of natural variation in male parenting. We find that socio-environmental conditions drive individual variation in male alloparenting such that post-weaning social isolation increases paternal care while social living in higher density groups increases infanticide. This natural variation in care corresponds to neural activity in the medial preoptic area and changes in correlated activity across brain regions. Within the medial preoptic area, expression of agouti signaling protein ( Agouti ) in neurons is increased by group housing and is negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant animals. Naturalistic manipulations further reveal that Agouti integrates long-term housing conditions rather than food availability/hunger. Together, our results demonstrate that Agouti acts as a molecular integrator of socio-environmental information to drive variation in paternal care.

  PublisherOA PDFDOI

• Conservation and alteration of mammalian striatal interneurons

  Nature · 2025-11-05 · 16 citations

  articleOpen access

  Mammalian brains vary in size, structure and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved1–4. Previous studies suggest that there is a primate-specific population of striatal inhibitory interneurons—the TAC3 interneurons5. However, broader taxonomic and developmental characterization is required to address novelty in cell-type evolution. Here we examine gene expression in inhibitory neurons across 10 mammalian species, spanning 160 million years of divergence from primates. We find that the initial class of newborn TAC3 interneurons specified during development represents an ancestral, medial ganglionic eminence (MGE)-derived striatal population that is also present in pig and ferret cortex. This discovery prompted a re-examination of Glires, including mice, which are thought to lack the TAC3 type5,6. Targeted enrichment of MGE precursors in mice revealed conservation of the TAC3 initial class, camouflaged by reduced expression of Tac2 (the mouse orthologue of TAC3) and a gain of Th expression. Extending our analysis to the adult striatum further supported the homology of primate TAC3 and mouse Th striatal interneurons, and also uncovered a rare Tac2 subpopulation in the mouse ventromedial striatum. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved, and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development. An analysis of cell-type diversity in brain samples from a variety of mammalian species, both during development and in adult animals, reveals that the TAC3 initial class of striatal interneurons is conserved across placental mammals and is homologous to Th striatal interneurons in rodents.

  PublisherOA PDFDOI

• Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates

  Science Advances · 2025-04-16 · 5 citations

  articleOpen accessSenior authorCorresponding

  Marsupial neonates are born with immature immune systems, making them vulnerable to pathogens. While neonates receive maternal protection, they can also independently combat pathogens, although the mechanisms remain unknown. Using the sugar glider ( Petaurus breviceps ) as a model, we investigated immunological defense strategies of marsupial neonates. Cathelicidins—a family of antimicrobial peptides expanded in the genomes of marsupials—are highly expressed in developing neutrophils. Sugar glider cathelicidins reside in two genomic clusters, and their coordinated expression is achieved by enhancer sharing within clusters and long-range physical interactions between clusters. Functionally, cathelicidins modulate immune responses and have potent antibacterial effects, sufficient to provide protection in a mouse model of sepsis. Evolutionarily, cathelicidins have a complex history, with marsupials and monotremes uniquely retaining both clusters among tetrapods. Thus, cathelicidins are critical mediators of marsupial immunity, and their evolution may reflect the life history–specific immunological needs of these animals.

  PublisherDOI

• Adaptations to water stress and pastoralism in the Turkana of northwest Kenya

  Science · 2025-09-18 · 5 citations

  article

  The Turkana pastoralists of Kenya inhabit arid, water-limited environments and rely largely on livestock for subsistence. Working with Turkana communities, we sequenced 367 whole genomes and identified eight regions with evidence for recent positive selection. One of these regions includes a putative regulatory element for STC1 —a kidney-expressed gene involved in metabolism and the response to dehydration. We show that STC1 is induced by antidiuretic hormone in human cells, is associated with urea levels in the Turkana themselves, and is under strong and recent selection in this population as well as a second East African population, the Daasanach. This work highlights how integrating anthropological and genomic approaches can lead to a new understanding of human physiology with biomedical relevance.

  PublisherDOI

• Patterns of Mitochondrial ATP Predict Tissue Folding

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-31

  preprintOpen access

  The construction of tissue shapes during embryonic development results from patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Time-lapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase at the apical side of epithelial cells before actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apical bias are conserved during apical constriction in flies, chicks, and mice, and these patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in development.

  PublisherOA PDFDOI

• Author Correction: Conservation and alteration of mammalian striatal interneurons

  Nature · 2025-12-11

  articleOpen access
  PublisherOA PDFDOI

• Marsupial immune protection is shaped by enhancer sharing and gene cluster duplication of cathelicidin antimicrobial peptides

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-30 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Marsupial neonates are born with immature immune systems, making them vulnerable to pathogens. While neonates receive maternal protection, they can also independently combat pathogens, though the mechanisms remain unknown. Using the sugar glider (Petaurus breviceps) as a model, we investigated immunological defense strategies of marsupial neonates. Cathelicidins, a family of antimicrobial peptides expanded in the genomes of marsupials, are highly expressed in developing neutrophils. Sugar glider cathelicidins reside in two genomic clusters and their coordinated expression is achieved by enhancer sharing within clusters and long-range physical interactions between clusters. These cathelicidins modulate immune responses and have potent antimicrobial effects, sufficient to provide protection in a mouse model of sepsis. Lastly, cathelicidins have a complex evolutionary history, where marsupials and monotremes are the only tetrapods that retained two cathelicidin clusters. Thus, cathelicidins are critical mediators of marsupial immunity, and their evolution reflects the life history-specific immunological needs of these animals.

  PublisherOA PDFDOI

• Genome-Wide Profiling of Cis-regulatory Elements in Mammalian Skin

  Methods in molecular biology · 2024-01-01

  articleSenior author
  PublisherDOI

• Emx2 underlies the development and evolution of marsupial gliding membranes

  Nature · 2024-04-24 · 22 citations

  articleOpen accessSenior author

  . However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium-an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis-regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis-regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty.

  PublisherDOI

Recent grants

• Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

  NIH · $3.0M · 2019–2030

Frequent coauthors

• Hopi E. Hoekstra

  Harvard University Press

  28 shared

• Charles Y. Feigin

  Princeton University

  15 shared

• Keith R. Willmott

  Florida Museum of Natural History

  15 shared

• Tess A. Linden

  Harvard University

  8 shared

• Jonathan S. Duke‐Cohan

  Harvard University

  8 shared

• Sarah A. Mereby

  Princeton University

  7 shared

• Christian F. Guerrero‐Juarez

  University of Illinois Urbana-Champaign

  7 shared

• Chris D. Jiggins

  University of Cambridge

  7 shared

Education

• PhD

  Harvard University

  2011

• BS

  Universidad de los Andes

  2003

Awards & honors

• 2021 Vallee Scholar
• 2019 Searle Scholar
• Sloan Fellow