Jeramiah Smith, PhD, Postdoctoral Fellow
Benaroya Research Institute at Virginia Mason
BRI – 141
1201 9th Ave.
Seattle, WA 98101
Office Telephone: (206) 583-6093
Fax: (206) 583-2297
E-mail: jsmith@benaroyaresearch.org
Smith Detailed Research Profile
Research
The unique selection pressures and functional constraints that vertebrate lineages have experienced over deep evolutionary time have resulted in a diversity of different mechanisms that mediate recombination (meiotic and mitotic), gene duplication, and the evolution of novel functional elements and developmental mechanisms. I am generally interested in understanding how vertebrate genomes evolve at the molecular level and how these changes contribute to the evolution of development. Ongoing studies take advantage of modifications that have accumulated through deep evolution in order to better understand how novel genomic functions arise and contribute to an organism’s biology. My current research can be broken into three overlapping areas:
1) Developmentally programmed rearrangement of the lamprey genome
2) Deep evolution and rearrangement of vertebrate genome structure
3) Evolution of recombinational variation and sex-chromosomes
My work in the Amemiya lab has been primarily focused on the discovery and characterization of programmed genome rearrangement events that occur during early embryogenesis in the lamprey (Petromyzon marinus). Somatic genome rearrangement is often a cause and consequence of cancers or other “genomic disorders”. However, a few metazoan and protist lineages are known to undergo tightly-regulated and large-scale somatic recombinations during the normal course of their development. The discovery of programmed genome rearrangement in lamprey (a vertebrate) fills an important gap in our understanding of dysregulated rearrangement of vertebrate genomes and the capacity for tight regulation of genome rearrangement other taxa. Several lines of evidence demonstrate that the lamprey undergoes a dramatic remodeling of its genome, resulting in the elimination of hundreds of millions of base pairs (~20% of the genome) from many somatic cell lineages during embryonic development. Embryological studies reveal that many of these rearrangements take place early in development, resulting in a situation wherein an individual’s “germline” and “somatic” cell lineages differ substantially in genome structure and gene content. Computational, array CGH (comparative genomic hybridization), and 454 sequencing studies reveal that several distinct genomic regions are altered during this process and have identified specific rearrangement breakpoints that differentiate germline and somatic genomes. Genomic regions that are removed via programmed rearrangements include hundreds of genes, many of which are transcribed in adult and juvenile testes or during early embryonic development. A large fraction of these somatically-deleted genes have homologs that are known to contribute to genome stability or the specification/maintenance of pluripotent cell lineages. Our studies of programmed genome rearrangement in lamprey can therefore provide unique insight into the rearrangement biology of vertebrate genomes and the genetics of somatic vs. germline cell fate.
REFEREED JOURNAL ARTICLES (* denotes equal contribution for primary authorship)
Smith JJ, Stuart A, Sauka-Spengler T, Clifton S, Amemiya CT. (2010) Development and analysis of a germline BAC resource for the sea lamprey, a vertebrate that undergoes substantial chromatin diminution. Chromosoma. (In Press).
Saha NR, Smith JJ, Amemiya CT. (2010) Evolution of adaptive immune recognition in jawless vertebrates. Seminars in Immunology. (Epub ahead of print).
Fitzpatrick BM, Johnson JR, Kump DK, Smith JJ, Voss SR, Shaffer HB (2010) Rapid spread of invasive genes into a threatened native species. PNAS (Epub ahead of print).
Smith JJ, Antonacci F, Eichler EE, Amemiya CT. (2009) Programmed loss of millions of base pairs from a vertebrate genome. PNAS 106:11212-11217. (This paper was recognized in several news articles, including ScienceNOW.org & Science 26 June 2009: Vol. 324. no. 5935, p. 1631).
Fitzpatrick BM, Johnson JR, Kump DK, Shaffer HB, Smith JJ and Voss SR (2009) Rapid fixation of non-native alleles revealed by genome-wide SNP analysis of hybrid tiger salamanders. BMC Evolutionary Biology 9:176.
Smith JJ, Voss SR. (2009) Amphibian sex determination: segregation and linkage analysis using members of the tiger salamander species complex (Ambystoma mexicanum and A. t. tigrinum). Heredity 102:542-548. (This paper was recognized in the issue highlights).
Smith JJ, Putta S, Zhu W, Pao GM, Verma I, Hunter T, Bryant SV, Gardiner DM, Harkins TT, Voss SR. -(2009) Genic regions of a large salamander genome contain long introns and novel genes. BMC Genomics 10:19.
Page RB, Voss SR, Samuels AK, Smith JJ, Putta S, Beachy CK. (2008) Effect of thyroid hormone concentration on the transcriptional response underlying induced metamorphosis in the Mexican axolotl (Ambystoma). BMC Genomics 9: 78.
Smith JJ, Voss SR. (2007) Bird and mammal sex chromosome orthologs map to the same autosomal region in a salamander (Ambystoma). Genetics 177: 607-613. (This paper was recognized in the issue highlights).
* Putta S, Smith JJ, Staben C, Voss SR. (2007) MapToGenome: a comparative genomic tool that aligns transcript maps to sequenced genomes. Evolutionary Bioinformatics Online 2: 15-25.
Smith JJ, Voss SR. (2006) Gene order data from a model amphibian (Ambystoma): new perspectives on vertebrate genome structure and evolution. BMC Genomics 7: 219.
Page RB, Monaghan JR, Samuels AK, Smith JJ, Beachy CK, Voss SR. (2006) Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum. Comparative Biochemistry and Physiology, Part C. 145: 15-27.
* Voss SR, Smith JJ. (2005) Evolution of salamander life cycles: A major-effect quantitative trait locus contributes to discrete and continuous variation for metamorphic timing. Genetics 170: 275-281. (This paper was highlighted by the Faculty of 1000 in Biology, June 2005).
Smith JJ, Putta S, Walker JA, Kump DK, Samuels AK, Monaghan JR, Weisrock DW, Staben C, Voss SR. (2005) Sal-Site: Integrating new and existing ambystomatid salamander research and informational resources. BMC Genomics 6: 181.
Smith JJ, Kump DK, Walker JA, Parichy DM, Voss SR. (2005) A comprehensive expressed sequence tag linkage map for tiger salamander and Mexican axolotl: enabling gene mapping and comparative genomics in Ambystoma. Genetics 171: 1161-1171.
Samuels AK, Weisrock DW, Smith JJ, France KJ, Walker JA, Putta S, Voss SR. (2005) Transcriptional and phylogenetic analysis of five complete ambystomatid salamander mitochondrial genomes. Gene 349: 43-53.
* Putta S, Smith JJ, Walker JA, Rondet M, Weisrock DW, Monaghan J, Samuels AK, Kump K, King DC, Maness NJ, Habermann B, Tanaka E, Bryant SV, Gardiner DM, Parichy DM, Voss SR. (2004) From biomedicine to natural history research: EST resources for ambystomatid salamanders. BMC Genomics 5: 54.
Voss SR, Smith JJ, Gardiner DM, Parichy DM. (2001) Conserved vertebrate chromosome segments in the large salamander genome. Genetics 158: 735-746.