Allan G. Force
force@vmresearch.org
http://www.vmresearch.org/lab_research/amemiya/force/aforce.htm

Chris T. Amemiya Lab
Department of Molecular Genetics
Virginia Mason Research Center
1201 Ninth Avenue
Seattle, WA 98101
USA

Former Advisors:
Dr. John Postlethwait, Institute of Neuroscience, UO
Dr. Michael Lynch, now at Indiana University

IGERT Trainee from 1999-2000

________________________

Research Interests

Allan earned his Ph.D. in 2000 and worked for 1 year as a postdoc in the lab of his Ph.D. advisor, John Postlethwait at the University of Oregon. He is now a postdoctoral fellow in the lab of Chris T. Amemiya at the Virginia Mason Research Center in Seattle, WA.

The origin of organismal complexity is generally thought to be tightly coupled to the evolution of new gene functions arising subsequent to gene duplication. Under the classical model for the evolution of duplicate genes, one member of the duplicated pair usually degenerates within a few million years by accumulating deleterious mutations, while the other duplicate retains the original function. This model further predicts that on rare occasions, one duplicate may acquire a new adaptive function, resulting in the preservation of both members of the pair, one with the new function and the other retaining the old. However, empirical data suggest that a much greater proportion of gene duplicates is preserved than predicted by the classical model. Here we present a new conceptual framework for understanding the evolution of duplicate genes that may help explain this conundrum. Focusing on the regulatory complexity of eukaryotic genes, we show how complementary degenerative mutations in different regulatory elements of duplicated genes can facilitate the preservation of both duplicates, thereby increasing long-term opportunities for the evolution of new gene functions. The duplication-degeneration-complementation (DDC) model predicts that (1) degenerative mutations in regulatory elements can increase rather than reduce the probability of duplicate gene preservation and (2) the usual mechanism of duplicate gene preservation is the partitioning of ancestral functions rather than the evolution of new functions. We present several examples (including analysis of a new engrailed gene in zebrafish) that appear to be consistent with the DDC model, and we suggest several analytical and experimental approaches for determining whether the complementary loss of gene subfunctions or the acquisition of novel functions are likely to be the primary mechanisms for the preservation of gene duplicates. For a newly duplicated paralog, survival depends on the outcome of the race between entropic decay and chance acquisition of an advantageous regulatory mutation.Sidow 1996(p. 717) On one hand, it may fix an advantageous allele giving it a slightly different, and selectable, function from its original copy. This initial fixation provides substantial protection against future fixation of null mutations, allowing additional mutations to accumulate that refine functional differentiation. Alternatively, a duplicate locus can instead first fix a null allele, becoming a pseudogene.Walsh 1995 (p. 426) Duplicated genes persist only if mutations create new and essential protein functions, an event that is predicted to occur rarely. Nadeau and Sankoff 1997 (p. 1259) Thus overall, with complex metazoans, the major mechanism for retention of ancient gene duplicates would appear to have been the acquisition of novel expression sites for developmental genes, with its accompanying opportunity for new gene roles underlying the progressive extension of development itself. Cooke et al. 1997 (p. 362)

________________________

Publications

Force, A. G., Cresko, W. A., and F. B. Pickett (2002) Informational accretion, gene duplication, and the mechanisms of genetic module parcellation. In Modularity in Development and Evolution , G. Schlosser and G. Wagner, eds., in press.

Force, A., Amores, A., and J. H. Postlethwait (2002) Hox cluster organization in the jawless vertebrate Petromyzon marinus. J. Exp. Zool. (Molecular and Developmental Evolution) 294: 30-46.

Lynch, M., M. O'Hely, B. Walsh, and A. Force  (2001) The probability of preservation of a newly arisen gene duplicate. Genetics 159:1789-1804.

Lynch, M., and A. Force (2000) Gene duplication and the origin of interspecific genomic incompatibility. Am. Nat. 156:590-605.

Lynch, M., and A. Force (2000) The probability of duplicate gene preservation by subfunctionalization. Genetics 154:459-73.

Force, A., M. Lynch, F.B. Pickett, A. Amores, Y.-L. Yan, and J. Postlethwait (1999) The preservation of duplicate genes by complementary degenerative mutations. Genetics 151:1531-1545.

Postlethwait, J., A. Amores, A. Force, and Y.-L. Yan (1999) The zebrafish genome. In The Zebrafish: Genetics and Genomics, H.W. Detrich, III, M. Westerfield, and L.I. Zon, eds., San Diego, CA: Academic Press, Meth. Cell Biol. 60:149-163.

Amores, A., A. Force, Y.-L. Yan, L. Joly, C. Amemiya, A. Fritz, R.K. Ho, J. Langeland, V. Prince, Y.-L. Wang, M. Westerfield, M. Ekker, and J.H. Postlethwait (1998) Zebrafish hox clusters and vertebrate genome evolution. Science 282:1711-1714.

Postlethwait, J.H., Y.-L. Yan, M. Gates, S. Horne, A. Amores, A. Brownlie, A. Donovan, E. Egan, A. Force, Z. Gong, C. Goutel, A. Fritz, R. Kelsh, E. Knapik, E. Liao, P. Paw, D. Ransom, A. Singer, M. Thomson, T.S. Abduljabbar, P. Yelick. D. Beier, J.-S. Joly, D. Larhammar, F. Rosa, M. Westerfield, L.I. Zon, S.L. Johnson, and W.S. Talbot (1998) Vertebrate genome evolution and the zebrafish gene map. Nature Genet. 18:345-349.

Arking, R., A.G. Force, S.P. Dudas. S. Buck, and G.T. Baker 3rd (1996) Factors contributing to the plasticity of the extended longevity phenotypes of Drosophila.  Exp Gerontol. 31:623-643.

Moens, C.B., Y.-L. Yan, B. Appel, A.G. Force, and C.B. Kimmel (1996)  valentino: a zebrafish gene required for normal hindbrain segmentation. Development 122: 3981-3990.

Force, A.G., T. Staples, S. Soliman, and R. Arking (1995) Comparative biochemical and stress analysis of genetically selected Drosophila strains with different longevities.   Dev Genet. 17:340-351.

Buck, S., M. Nicholson, S. Dudas, R. Wells, A. Force, G.T. Baker 3rd, and R. Arking (1993) Larval regulation of adult longevity in a genetically-selected long-lived strain of Drosophila.   Heredity 71:23-32.