Marian Goldsmith

Biography

We are developing genetic and genomic resources for Lepidoptera (moths and butterflies). Our main focus is constructing molecular linkage maps for the domesticated silkworm, Bombyx mori, the central model for lepidopteran genetics and genomics. Silkworm linkage maps are composed of a variety of molecular markers which can be amplified by PCR, including RAPDs, microsatellites, STSs, and CAPS, as well as RFLPs and SNPs. The linkage maps have many applications, including cloning silkworm mutations of interest and analyzing quantitative traits (or QTL) for silk production, such as body size, cocoon shell weight, and timing of metamorphosis. We are engaged in both kinds of studies, as well as in developing anchor loci for comparative genome analysis.

A second project is construction of large-fragment DNA or Bacterial Artificial Chromosome (BAC) libraries for other model lepidopterans, notably the tobacco hornworm, Manduca sexta, the mimetic butterfly, Heliconius erato, and the agricultural pest, Heliothis virescens. BACs are used for cloning and analyzing full-length genes and their regulatory sequences. They are also used for constructing large-scale physical maps which can be integrated with genetic maps to aid in assembling whole genome shotgun sequences and for positional or map-based cloning of genes or mutations known only by their biological or phenotypic effects. The use of fluorescently-tagged BACs as probes for direct visualization of genes on chromosomes, or BAC-FISH (Fluorescence In Situ Hybridization), has led to a renaissance in lepidopteran cytogenetics, enabling rapid construction of physical maps for species such as the tobacco hornworm for which no genetic maps are available.

A relatively recent use of molecular genetic and BAC-FISH maps is to explore the extent of “synteny,” or conserved chromosome relationships among Lepidoptera. Early ancestors of moths and butterflies are estimated to be at least 100 million years old, leaving ample time for changes in chromosome organization. Finding a high level of synteny would enable investigators to use the well-established silkworm maps to pinpoint where to look for genes or mutations of interest in less well-characterized species, facilitating many kinds of studies. One that we are engaged in is mapping a mutation we found in silkworm with colleagues in Japan that confers resistance to Bt toxin, a class of insecticidal proteins produced by the bacterium, Bacillus thuringiensis, during sporulation. Crops genetically engineered to express Bt toxins are widely planted, presenting substantial risks for pests to evolve resistance in the field. If synteny is extensive among Lepidoptera, then identifying Bt-resistance gene(s) in silkworm could significantly speed up identification of similar mutations in pests, enabling new ways to monitor the rise of resistance in pests eating Bt-crops and, potentially, leading to the development of better Bt-based insecticides.

Research

Genetic mapping and genomics in Lepidopter

Education

Ph.D. 1970, University of Pennsylvania
B.A. 1964, University of Rochester

Selected Publications

  1. Ahola V, Lehtonen R, Somervuo P, Salmela L, Koskinen P, Rastas P, Välmäki N, Paulin L, Dvish J, Wahlberg N, Tanskanen J, Hornett EA, Ferguson LC, Luo S, Cao Z, deJohn MA, Duplouy A, Smolander )-P, Vogel H, McCoy R, Qian K, Chong WS, Zhang Q, Ahmad F, Haukka JK, Joshi A, Saloja J, Salojärvi J, Wheat CW, Grosse-Wilde E, Waterhouse RM, Turunen M, Vaähaärautio A, Ojanen SP, Schulman AH, Taipale M, Lawson D, Ukkonen E, Maäkinen V, Goldsmith MR, Holm Liisa, Auvinen P, Frilander M, Hanski I. 2014. The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera. Nat Commun 5:4737; doi:10.1038/ncomms5737
  2. Suetsugu Y, Futahashi R, Kanamori H, Kadono-Okuda K, Sasanuma S, Narukawa J, Ajimura M, Jouraku A, Namiki N, Shimomura M, Sezutsu H, Osanai-Futahashi M, Suzuki MG, Daimon T, Shinoda T, Taniai K, Asaoka K, Niwa R, Kawaoka S, Katsuma S, Tamura T, Noda H, Kasahara M, Sugano S, Suzuki Y, Fujiwara H, Kataoka H, Arunkumar KP, Tomar A, Nagaraju J, Goldsmith MR, Feng Q, Xia Q, Yamamoto K, Shimada T, Mita K. Large scale full-length cDNA sequencing reveals a unique genomic landscape in a lepidopteran model insect, Bombyx mori. 2013. G3 (Bethesda), 3:1481-92
  3. i5K Consortium. 2013. The i5K Initiative: advancing arthropod genomics for knowledge, human health, agriculture, and the environment. J Hered, 104:595-600
  4. Atsumi S, Miyamoto K, Yamamoto K, Narukawa J, Kawai S, Sezutsu H, Kobayashi I, Uchino K, Tamura T, Mita K, Kadono-Okuda K, Wada S, Kanda K, Goldsmith MR, Noda H. 2012. Single amino acid mutation in an ATP-binding cassette transporter gene causes resistance to Bt toxin Cry1Ab in the silkworm, Bombyx mori. Proc Natl Acad Sci USA, 109(25):E1591-8; www.pnas.org/cgi/doi/10.1073/pnas.1120698109
  5. Liu C, Yamamoto K, Cheng TC, Kadono-Okuda K, Narukawa J, Liu SP, Han Y, Futahashi R, Kidokoro K, Noda H, Kobayashi I, Tamura T, Ohnuma A, Banno Y, Dai FY, Xiang ZH, Goldsmith MR, Mita K, Xia QY. 2010. Repression of tyrosine hydroxylase is responsible for the sex-linked chocolate mutation of the silkworm, Bombyx mori. Proc Natl Acad Sci USA, 107:12980-5.
  6. Goldsmith, M. R. 2010. Chapter 2, Recent progress in silkworm genetics and genomics. In Molecular Biology and Genetics of the Lepidoptera, ed’s M. R. Goldsmith and F. Marec. Boca Raton: CRC Press, pp. 25–47.
  7. Goldsmith, M. R. and Marec, F., editors. 2010. Molecular Biology and Genetics of the Lepidoptera. Boca Raton: CRC Press. 362 pp.
  8. Yasukochi Y., M. Tanaka-Okuyama, F. Shibata, A. Yoshido, F. Marec, C. Wu, H. Zhang, M. R. Goldsmith, and K. Sahara. 2009. Extensive conserved synteny of genes between the karyotypes of Manduca sexta and Bombyx mori revealed by BAC-FISH mapping. PLoS One 4(10):e7465.
  9. Shimomura M, Minami H, Suetsugu Y, Ohyanagi H, Satoh C, Antonio B, Nagamura Y, Kadono-Okuda K, Kajiwara H, Sezutsu H, Nagaraju J, Goldsmith MR, Xia Q, Yamamoto K, Mita K.. 2009. KAIKObase: An integrated silkworm genome database and data mining tool. BMC Genomics, 10:486.
  10. Wu, C, D. Proestou, D. Carter, E. Nicholson, F. Santos, S. Zhao, H-B. Zhang, and M. R. Goldsmith. 2009. Construction and sequence sampling of deep-coverage, large-insert BAC libraries for three model lepidopteran species. BMC Genomics 10: 283.
  11. Zhan, S., J. Huang, Q. Guo, Y. Zhao, W. Li, X. Miao, M. R. Goldsmith, M. Li, and Y. Huang. 2009. An integrated genetic linkage map for silkworms with three parental combinations and its application to the mapping of single genes and QTL. BMC Genomics 10:389.
  12. Proestou, D., M. R. Goldsmith, and S. Twombly. 2008. Patterns of male reproductive success in Crepidula fornicata provide new insight for sex allocation and optimal sex change. Biological Bulletin, 214: 194-202. (http://www.biolbull.org/cgi/content/abstract/214/2/194)
  13. Yamamoto, K., et al. 2008. A BAC-based integrated map of the silkworm, Bombyx mori. Genome Biology 9:R21 (doi:10.1186/gb-2008-9-1-r21).