Joanna Masel

Joanna Masel

Professor, Ecology and Evolutionary Biology
Professor, Genetics - GIDP
Professor, Statistics-GIDP
Professor, Applied Mathematics - GIDP
Professor, Psychology
Member of the Graduate Faculty
Professor, BIO5 Institute
Primary Department
(520) 626-9888

Research Interest

Joanna Masel, D.Phil., is a Professor of Ecology & Evolutionary Biology, applying the tools of theoretical population genetics to diverse research problems. Her research program is divided between analytical theory, evolutionary simulations, and dry lab empirical bioinformatic work. The robustness and evolvability of living systems are major themes in her work, including questions about the origins of novelty, eg at the level of new protein-coding sequences arising during evolution from "junk" DNA. She also has interests in prion biology, and in the nature of both biological and economic competitions. She has won many awards, including a Fellowship at Wissenschaftskolleg zu Berlin, a Pew Scholarship in the Biomedical Sciences, an Alfred P. Sloan Research Fellow, a Rhodes Scholarship, and a Bronze Medal at the International Mathematical Olympiad.


Andreatta, M. E., Levine, J. A., Foy, S. G., Guzman, L. D., Kosinski, L. J., Cordes, M. H., & Masel, J. (2015). The Recent De Novo Origin of Protein C-Termini. Genome biology and evolution, 7(6), 1686-701.
BIO5 Collaborators
Matthew Hj Cordes, Joanna Masel

Protein-coding sequences can arise either from duplication and divergence of existing sequences, or de novo from noncoding DNA. Unfortunately, recently evolved de novo genes can be hard to distinguish from false positives, making their study difficult. Here, we study a more tractable version of the process of conversion of noncoding sequence into coding: the co-option of short segments of noncoding sequence into the C-termini of existing proteins via the loss of a stop codon. Because we study recent additions to potentially old genes, we are able to apply a variety of stringent quality filters to our annotations of what is a true protein-coding gene, discarding the putative proteins of unknown function that are typical of recent fully de novo genes. We identify 54 examples of C-terminal extensions in Saccharomyces and 28 in Drosophila, all of them recent enough to still be polymorphic. We find one putative gene fusion that turns out, on close inspection, to be the product of replicated assembly errors, further highlighting the issue of false positives in the study of rare events. Four of the Saccharomyces C-terminal extensions (to ADH1, ARP8, TPM2, and PIS1) that survived our quality filters are predicted to lead to significant modification of a protein domain structure.

Teufel, A. I., Masel, J., & Liberles, D. A. (2015). What Fraction of Duplicates Observed in Recently Sequenced Genomes Is Segregating and Destined to Fail to Fix?. GENOME BIOLOGY AND EVOLUTION, 7(8), 2258-2264.
Clarke, A. R., Jackson, G. S., Collinge, J., Pepys, M. B., Barron, L. D., Masel, J., Tahari-Alaoui, A., Lansbury, P., Dobson, C. M., Exley, C., & Feizi, T. (2001). The molecular biology of prion propagation. Philosophical Transactions of the Royal Society B: Biological Sciences, 356(1406), 185-195.

PMID: 11260799;PMCID: PMC1088424;Abstract:

Prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals are associated with the accumulation in affected brains of a conformational isomer (PrPSc) of host-derived prion protein (PrPC). According to the protein-only hypothesis, PrPSc is the principal or sole component of transmissible prions. The conformational change known to be central to prion propagation, from a predominantly α-helical fold to one predominantly comprising β structure, can now be reproduced in vitro, and the ability of β-PrP to form fibrillar aggregates provides a plausible molecular mechanism for prion propagation. The existence of multiple prion strains has been difficult to explain in terms of a protein-only infectious agent but recent studies of human prion diseases suggest that strain-specific phenotypes can be encoded by different PrP conformations and glycosylation patterns. The experimental confirmation that a novel form of human prion disease, variant CJD, is caused by the same prion strain as cattle BSE, has highlighted the pressing need to understand the molecular basis of prion propagation and the transmission barriers that limit their passage between mammalian species. These and other advances in the fundamental biology of prion propagation are leading to strategies for the development of rational therapeutics.

Kelly, S., Bliss, T. M., Shah, A. K., Sun, G. H., Ma, M., Foo, W. C., Masel, J., Yenari, M. A., Weissman, I. L., Uchida, N., Palmer, T., & Steinberg, G. K. (2004). Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America, 101(32), 11839-11844.

PMID: 15280535;PMCID: PMC511061;Abstract:

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (≈1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker β-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

Masel, J., & Griswold, C. K. (2009). The strength of selection against the yeast prion [PSI +]. Genetics, 181(3), 1057-1063.

PMID: 19153253;PMCID: PMC2651042;Abstract:

The [PSI +] prion causes widespread readthrough translation and is rare in natural populations of Saccharomyces, despite the fact that sex is expected to cause it to spread. Using the recently estimated rate of Saccharomyces outcrossing, we calculate the strength of selection necessary to maintain [PSI +] at levels low enough to be compatible with data. Using the best available parameter estimates, we find selection against [PSI +] to be significant. Inference regarding selection on modifiers of [PSI +] appearance depends on obtaining more precise and accurate estimates of the product of yeast effective population size N e and the spontaneous rate of [PSI +] appearance m. The ability to form [PSI +] has persisted in yeast over a long period of evolutionary time, despite a diversity of modifiers that could abolish it. If mN ee gt; 1, then selection should favor the spread of [PSI +] resistance modifiers. In this case, rare conditions where [PSI +] is adaptive may permit its persistence in the face of negative selection. Copyright © 2009 by the Genetics Society of America.