Nathan M. Springer

Research Interests

I am interested in understanding the sources of heritable phenotypic variation within a species. My lab focuses on studying the genetic and epigenetic mechanisms that lead to variation in gene expression levels. Genetic changes can lead to altered gene expression through variation in cis-acting or trans-acting factors. Epigenetic mechanisms of gene regulation are not based on sequence specific regulation. The molecular basis of epigenetic regulation occurs through the modification of chromatin states, such as DNA methylation or histone modifications. Maize provides an excellent model system for our studies due to the ease of performing genetic analyses and the complex genome with a mixture of genes and transposable elements.

One current focus of my lab is understanding the prevalence and consequences of structural variation within a species.  We are using high density microarrays to compare the structure of the genome in different maize inbred lines to identify examples of copy number variation (CNV) and presence-absence variation (PAV).  CNV and PAV are examples of differences in the copy number, or presence, of sequences in different members of the same species.  We have found that nearly 10% of maize genes vary in copy number or presence.  This structural variation may contribute to heterosis and phenotypic variation.

Epigenomic variation is another focus of our research.  We are studying the patterns of DNA methylation and histone modifications in different maize inbreds to identify examples of variation in epigenetic patterns.  We have found that epigenetic variation is much more prevalent among different genotypes than among different tissues or developmental stages.  Current research is focused on studying the effects and heritability of this epigenetic variation to understand how it contributes to phenotypic variation within the maize species.

In addition, my lab has active research projects on gene expression variation, imprinting, aneuploid syndromes.  We are also applying new technologies to perform sequence capture of target sequences, rapid mapping of mutants and allele-specific gene expression analyses.  My long-term goals are to understand the contribution of epigenetics to heritable variation and to understand how molecular variation can lead to phenotypic heterosis.  

Selected Publications

Schnable JC, Springer NM, Freeling M. 2011. Differentiation of the maize subgenomes by genome dominance and both ancient and ongoing gene loss. Proc Natl Acad Sci U S A. 108:4069-74.

Swanson-Wagner RA, Eichten SR, Kumari S, Tiffin P, Stein JC, Ware D, Springer NM. 2010. Pervasive gene content variation and copy number variation in maize and its undomesticated progenitor. Genome Res. 20:1689-99.

Lai J, Li R, Xu X, Jin W, Xu M, Zhao H, Xiang Z, Song W, Ying K, Zhang M, Jiao Y, Ni P, Zhang J, Li D, Guo X, Ye K, Jian M, Wang B, Zheng H, Liang H, Zhang X, Wang S, Chen S, Li J, Fu Y, Springer NM, Yang H, Wang J, Dai J, Schnable PS, Wang J. 2010. Genome-wide patterns of genetic variation among elite maize inbred lines. Nat Genet. 42:1027-30

Springer NM, Ying K, Fu Y, Ji T, Yeh C-T, Jia Y, Wu W, Richmond T, Kitzman J, Rosenbaum H, Iniguez AL, Barbazuk WB, Jeddeloh JA, Nettleton D, Schnable PS. 2009. Maize Inbreds Exhibit High Levels of CNV and Presence/Absence Differences in Genome Content. PLoS Genetics 5(11): e1000734.

Flint-Garcia SA, Buckler ES, Tiffin P, Ersoz E, Springer NM. 2009. Heterosis is prevalent for multiple traits in diverse maize germplasm. PLoS One 4:e7433.

Haun WJ, Springer NM.  2008.  Maternal and paternal alleles exhibit differential histone methylation and acetylation at the maize imprinted genes.  The Plant Journal 56: 903-912
Makarevitch I, Phillips RL, Springer NM.  2008.  Profiling expression changes caused by a segmental aneuploid in maize.  BMC Genomics 9:7.

Makarevitch I, Stupar RM, Iniguez AL, Haun WJ, Barbazuk WB, Kaeppler SM, Springer NM.  2007.  Natural variation for alleles under epigenetic control by the maize chromomethylase Zmet2.  Genetics 177:749-60.

Haun WJ, Laoueille-Duprat S, O’Connell MJ, Spillane C, Grossniklaus U, Phillips AR, Kaeppler SM, Springer NM. 2007. Genomic imprinting, methylation and molecular evolution of maize Enhancer of zeste (Mez) homologs.  The Plant Journal 49: 325-337.

Stupar RM, Springer NM.  2006.  Cis-transcriptional variation in maize inbred lines B73 and Mo17 leads to additive expression patterns in the F1 hybrid.  Genetics 173:2199-2210.