Lucia Carbone

Large-scale chromosomal rearrangements are key drivers of mammalian genome evolution. These events are a major source of genetic variation, bring about speciation, and are hallmarks of human disease, but the mechanisms underlying their occurrence and subsequent fixation are not entirely understood. What are the mechanisms through which specific genomic features lead to chromosomal rearrangements? Why do some species display a substantially higher rate of chromosomal rearrangements compared to closely related species?

Dr. Carbone investigates these questions using comparative genomics and bioinformatics approaches and a non-human primate model: the gibbon. Gibbons are hominoids that share a common ancestor with humans relatively recently (17 million years ago, mya). They are also the most species-rich hominoids (19 species), suggesting a peculiar evolutionary history, distinct from that of the other apes. Notably, synteny between the gibbon and great ape genomes has been shattered by numerous chromosomal rearrangements that have occurred in the gibbon lineage. These rearrangements also distinguish the four gibbon genera (Nomascus, Hoolock, Symphalangus, Hylobates), which diverged from each other only 5 mya but carry four different karyotypes, with numbers of chromosomes ranging from 38 to 52. For these reasons, the gibbon represents a unique model to study mechanisms underlying chromosomal rearrangements, the impact that these mutations have on the evolution of functional sequences and species radiation.

Working with several national and international collaborators and through her independent research program, Dr. Carbone investigates the underlying mechanism of chromosomal rearrangements and how these events affect genome and species evolution. First, she aims to define the relationship between epigenetic marks, chromatin states, and chromosomal rearrangements and determine how these events correlate with evolution of chromosomal domains. The gibbon is an ideal model to address this question because its rapid divergence from human is very recent and genomic regions are likely to display signatures of selection. Moreover, its karyotype showcases numerous chromosomal rearrangements whose breakpoints have been characterized at the highest resolution (Carbone et al. 2009).Second, she aims to study how the new and active LAVA retroelement (Carbone et al. 2012) has been influencing distinctive gibbon specific traits (e.g. chromosomal rearrangements, brachiation) and test the hypothesis that some of these insertions might be adaptive. The goal is to address the more general question of how the emergence of novel mobile elements can influence the transcriptome, epigenome and, consequently the establishment of species-specific traits. Finally, she is interested in studying chromosomal speciation and learn more about the evolutionary history of gibbons.

Together with her deep interest in studying basic evolutionary processes, Dr. Carbone seeks to translate the knowledge gleaned from evolutionary studies to human health. Accumulation of chromosomal imbalances is a characteristic of human tumors, early embryonic development, and aging. To this point, she has been leveraging the rhesus monkey model and the resources available at the Oregon National Primate Research Center (ONPRC). In collaboration with scientists from different fields (e.g. reproductive science, neuroscience), she has expanded her research program to address fundamental questions related to the effects of chromosome aberrations in both embryonic undifferentiated cells (i.e.blastomeres) and somatic differentiated cells (i.e. neurons and glia).   



Lucia Carbone is an Assistant Professor in the Department of Medicine at OHSU and has a joint appointment as an Assistant Professor in the Division of Neuroscience (Primate Genetics Section) at ONPRC. She received an M.S. in Biology in 2001 and a Ph.D. in Genetics and Molecular Evolution in 2004 from the University of Bari, Italy. She was a Postdoctoral Fellow and an Assistant Staff Scientist at the Children's Hospital Oakland Research Institute (CHORI) from 2005-2010. Her postdoctoral research focused on the karyotype evolution in gibbon species (Hylobatidae) in order to uncover factors contributing to genome instability in primates. She led the International Consortium for the Sequencing and Annotation of the gibbon genome whose results were published in Nature in 2014. Besides running her own lab, she is currently Director of the epigenetics consortium for the Knight Cardiovascular Institute at OHSU and the Biostatistics and Bioinformatics Unit at the ONPRC.



Carbone L, Harris RA, Gnerre S, Veeramah KR, Lorente-Galdos B, Huddleston J, Meyer TJ, Herrero J, Roos C, Aken B, Anaclerio F, Archidiacono N, Baker C, Barrell D, Batzer MA, Beal K, Blancher A, Bohrson CL, Brameier M, Campbell MS, Capozzi O, Casola C, et al. Gibbon genome and the fast karyotype evolution of small apes. Nature. 2014 Sep 11;513(7517):195-201.

Lucia Carbone, R. Alan Harris, Alan R. Mootnick, Aleksandar Milosavljevic, David IK. Martin, Mariano Rocchi, Oronzo Capozzi, Nicoletta Archidiancono, Mariam K. Konkel, Jerilyn A. Walker, Mark A. Batzer and Pieter J. de Jong (2012) Centromere remodeling in Hoolock leuconedys (Hylobatidae) by a new transposable element unique to the gibbons. Genome Biol Evol. 2012;4(7):648-58.

Carbone L, Harria RA, Vassere GM, Mootnick AR, Humphray S, Rogers J, Kim SK, Wall JD, Marin D, Jurka J, Milosavlievic A, de Jong PJ (2009) Evolutionary breakpoints in the gibbon suggest association between cytosine methylation and karyotype evolution. PLoS Genet. 5(6):e1000538.

Carbone L, Vessere GM, ten Hallers BF, Zhu B,Osoegawa K, Mootnick A, Kofler A, Wienberg J, Rogers J. Humphray S, Scott C, Harris RA, Milosavlievic A, de Jong PJ (2006) A high-resolution of synteny disruptions in gibbon and human genomes. PloS Genet. 2(12):e223.

See a full listings of Dr. Carbone's publications.