Benaroya Research Institute at Virginia Mason

&

University of Washington, Department of Genome Sciences

BRI – 141

1201 9th Ave.

Seattle, WA 98101

Office Telephone: (206) 583-6093

Fax: (206) 583-2297

E-mail: jeramiahsmith [AT] gmail.com

 

Click here to download a pdf of my CV                  

 

Research

Evolution of Recombination and Genome Structure: 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 the deep evolutionary history of key vertebrate groups (including lamprey and salamander) 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

Developmentally Programmed Genome Rearrangements: This line of research is 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. Our 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 in other taxa (e.g. roundworms and ciliates).

  We have shown that programmed rearrangements result 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. Genomic regions that are removed via programmed rearrangements include hundreds of genes, many of which are transcribed in adult and juvenile testes or in during early embryonic development. A large fraction of these germline-specific (i.e. somatically-deleted) genes have homologs that are known to contribute to genome stability or the specification and maintenance of pluripotent cell lineages. Studies of programmed genome rearrangement in lamprey can therefore provide unique insight into several critical areas of biological inquiry, including: regulation of recombination in vertebrate genomes, carcinogenesis, and the genetics of pluripotency.

Ongoing studies are leveraging 2^nd generation sequence data and functional/ embryological studies in order to better understand the molecular basis of genome rearrangement and the biological functions of germline-specific genes.

Developing Genome Resources for Highly-Informative Vertebrate Genomes: A second major focus of the lab is the development of genome resources for two highly-informative vertebrate groups (lamprey and salamander). These species provide insight into key periods in vertebrate evolution and important aspects of vertebrate genome biology.

Lamprey

Lamprey diverged from the rest of the vertebrate lineage approximately 0.5 billion years ago and provides critical insight into the genome structure and developmental biology of the ancestral lineage that gave rise to all vertebrates. Moreover, it is the only vertebrate genome that is known to undergo large-scale programmed rearrangement. We are nearing completion of the first draft of the lamprey genome and are moving on to better characterize the large-scale structure. Ongoing work is aimed at resolving large-scale (megabase) linkages within the existing assembly, gap filling, resolving the sequence of the germline genome (the current assembly represents the somatic genome, which is a rearranged and reduced version of the germline genome, see above) and performing computation analyses of the two genomes. This work is being performed in collaboration with the lamprey sequencing consortium and the Amemiya lab. 

 

Salamander

The amphibian lineage (including salamander) diverged from all other tetrapods (legged vertebrates) approximately 300 million years ago and provides insight into the biology of the ancestral tetrapod. The salamander genome is one of the largest vertebrate genomes, but has otherwise undergone very little change in genome structure since divergence from the ancestral tetrapod lineage. Moreover, salamander possesses very recently-evolved sex determining system with sex chromosomes are in the earliest steps of an evolutionary path that is expected to result in dramatic structural divergence (i.e. the human X and Y chromosomes). The salamander genome can therefore provide numerous insights into the evolution and functionality of changes in genome size, gene order, and chromosome structure within vertebrates. We have established a large-scale genetic map for salamander and are currently undertaking the initial efforts toward the large-scale sequencing project. This work is being performed in collaboration with the Voss lab and the salamander genome consortium. 

Publications (* denotes equal contribution for primary authorship)

(19)   Voss SR, Kump DK, Putta S, Pauly N, Reynolds A, Henry R, Basa S, Walker JA, Smith JJ. (2011) Origin of amphibian and avian chromosomes by fission, fusion, and retention of ancestral chromosomes. Genome Research. Published in Advance April 11, 2011

(18)   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 119:381-389.  

(17)   Fitzpatrick BM, Johnson JR, Kump DK, Smith JJ, Voss SR, Shaffer HB (2010) Rapid spread of invasive genes into a threatened native species. PNAS 107:3606-3610.

(16)   Saha NR, Smith JJ, Amemiya CT. (2010) Evolution of adaptive immune recognition in jawless vertebrates. Seminars in Immunology 22:25-33.

(15)   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.

(14)   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).

(13)   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).

(12)   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.

(11)   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.

(10)   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).

(9)   * 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.

(8)   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.

(7)   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.

(6)   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.

(5)   * 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).

(4)   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.

(3)   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.

(2)   * 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.

(1)   Voss SR, Smith JJ, Gardiner DM, Parichy DM. (2001) Conserved vertebrate chromosome segments in the large salamander genome. Genetics 158: 735-746.