How do genomes change during evolution? To what extent are mechanisms responsible for evolutionary changes also relevant to human disease? Much is understood about fine-scale genomic changes (e.g. point mutations), but the mechanisms of large-scale chromosomal rearrangements (inversion, translocation, fission and fusion) are still unknown. Large-scale chromosome changes are key events in speciation and cancer; therefore it is critical to define how they occur, and their impact on genome architecture.
Dr. Carbone's research has focused on chromosome evolution, particularly centromere repositioning and chromosomal rearrangements, and has recently highlighted a deep similarity between the sources of chromosome instability in species evolution and cancer. To learn about the causes of chromosomal rearrangements, she has studied chromosome evolution in gibbons, a family of primate species closely related to the great apes (human, chimpanzee, gorilla and orangutan). During the evolution of the gibbon species, there has been an exceptionally high frequency of chromosomal rearrangements, which is not explained by current models of chromosome evolution. Dr. Carbone's research has uncovered evidence that this phenomenon may have been driven by a defect in epigenetic controls.
Epigenetic modifications are not reflected in the DNA sequence, but may nevertheless be heritable. Transposable Elements (TEs) often have deleterious effects on the integrity of the genome and cytosine methylation is a key epigenetic modification used by vertebrates to repress their activity. The study of chromosomal breakpoints in gibbon species revealed that TEs at the breakpoints are undermethylated when compared to their homologous human sequences. The significance of this observation is highlighted by the occurrence of a similar phenomenon in cancer cells. Cancer cells genomes are both globally hypomethylated and heavily rearranged, but no direct correlation between the two phenomena has yet been experimentally validated.
One of the goals of the Carbone lab is to explore a mode of chromosome evolution in which the impairment of epigenetic repression of transposable elements causes a higher frequency of chromosomal rearrangements. The long-term strategy will be to use insights gleaned from species comparisons to understand the mechanism of chromosomal rearrangement in cancer, in combination with studies on cancer patients. The research in Carbone lab will benefit from innovative technologies, as massively parallel sequencing, and will contribute to the development of new tools for data production and analysis.
Lucia Carbone is an Assistant Professor in the Behavioral Neuroscience Department at Oregon Health and Science University (OHSU) and has a joint appointment as an Assistant Scientist in the Division of Neuroscience at the Oregon National Primate Research Center (ONPRC). She received a 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 is currently leading the International Consortium for the Sequencing and Annotation of the gibbon genome.
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.
Oronzo Capozzi*, Lucia Carbone*, Roscoe R. Stanyon, Annamaria Marra, Fengtang Yang, Christopher W. Whelan, Pieter J. de Jong, Mariano Rocchi and Nicolette Archidiacono (2012) A Comprehensive Molecular Cytogenetic Analysis of Chromosome Rearrangements in Gibbons. Genome Res. 2013 Dec;22(12):250-8. *equal contribution.
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.