The broad objectives of this proposal are to elucidate the mechanisms that promote stability and change within vertebrate genomes. This knowledge is critical for understanding how the integrity of information encoded in the human genome is maintained and passed from cell to cell. Disruption of the numerous mechanisms that participate in the maintenance of genome structure is the root cause of many types of cancers and other genomic disorders. Many complimentary systems will need to be developed in order to more fully appreciate the diversity of mechanisms that participate in the maintenance of genome integrity, and mediate the rearrangement of DNA sequences. Indeed, the NIH has recognized the importance of developing non-mammalian model systems for comparative and functional genomic studies. The sea lamprey (Petromyzon marinus) is emerging as an attractive system for understanding the fundaments of vertebrate biology and was chosen by the NIH and NHGRI for whole genome sequencing, in order to facilitate further research using this important vertebrate lineage. This proposal builds on recently experimental developments that reveal the lamprey's novel genome biology. The lamprey undergoes dramatic changes in the architecture of its genome that occur as a feature of its normal development. This results in a situation wherein nearly every somatic tissue possesses a genome that is dramatically different from its germline precursor (i.e.sperm). These rearrangements occur at a massive (genome-wide) scale, are highly predictable, and are regulated during normal development.
The specific aims of this proposal are to expand this newly discovered information about the lamprey genome such that we can begin to understand the molecular causes and consequences of these rearrangements in lamprey and ultimately translate these into a better understanding of the mechanisms by which rearrangements of the human genome are and can be regulated. LAY SUMMARY: Tight maintenance of genome structure is critical for maintenance of health and survival. Some exceptional species undergo dramatic changes in their genome structure that mimic disease causing changes. Proposed research is targeted at the genome of one of these species (the sea lamprey) and strives to better understand how such dramatic changes are regulated and affect the biology of this non- human model of basal vertebrate development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM087919-02
Application #
7858375
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Carter, Anthony D
Project Start
2009-04-16
Project End
2010-08-15
Budget Start
2010-04-16
Budget End
2010-08-15
Support Year
2
Fiscal Year
2010
Total Cost
$18,133
Indirect Cost
Name
Benaroya Research Institute at Virginia Mason
Department
Type
DUNS #
076647908
City
Seattle
State
WA
Country
United States
Zip Code
98101
Smith, Jeramiah J; Timoshevskaya, Nataliya; Ye, Chengxi et al. (2018) The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution. Nat Genet 50:270-277
Smith, Jeramiah J; Kuraku, Shigehiro; Holt, Carson et al. (2013) Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat Genet 45:415-21, 421e1-2
Decatur, Wayne A; Hall, Jeffrey A; Smith, Jeramiah J et al. (2013) Insight from the lamprey genome: glimpsing early vertebrate development via neuroendocrine-associated genes and shared synteny of gonadotropin-releasing hormone (GnRH). Gen Comp Endocrinol 192:237-45
Morey, Kevin J; Antunes, Mauricio S; Barrow, Matt J et al. (2012) Crosstalk between endogenous and synthetic components--synthetic signaling meets endogenous components. Biotechnol J 7:846-55
Smith, Jeramiah J; Sumiyama, Kenta; Amemiya, Chris T (2012) A living fossil in the genome of a living fossil: Harbinger transposons in the coelacanth genome. Mol Biol Evol 29:985-93
Smith, J J; Netuveli, G; Sleight, S P et al. (2012) Development of a social morbidity score in patients with chronic ulcerative colitis as a potential guide to treatment. Colorectal Dis 14:e250-7
Smith, Jeramiah J; Baker, Carl; Eichler, Evan E et al. (2012) Genetic consequences of programmed genome rearrangement. Curr Biol 22:1524-9
Smith, J J; Saha, N R; Amemiya, C T (2010) Genome biology of the cyclostomes and insights into the evolutionary biology of vertebrate genomes. Integr Comp Biol 50:130-7
Smith, Jeramiah J; Stuart, Andrew B; Sauka-Spengler, Tatjana et al. (2010) Development and analysis of a germline BAC resource for the sea lamprey, a vertebrate that undergoes substantial chromatin diminution. Chromosoma 119:381-9
Smith, Jeramiah J; Antonacci, Francesca; Eichler, Evan E et al. (2009) Programmed loss of millions of base pairs from a vertebrate genome. Proc Natl Acad Sci U S A 106:11212-7