A major puzzle in biology is the origin of novel phenotypes. Innovative phenotypes are important to understanding medically important phenomena such as host-parasite interactions and the development of antibiotic resistance in pathogens. Classic models hold that mutational processes generate new phenotypes through gene duplication, domain shuffling, and other mechanisms that modify existing genes rather than making new ones. Random sequences may be prone to toxic aggregation rather than folding to a functional state: this is a major reason why """"""""tinkering"""""""" mechanisms have been posited. However, recent discoveries, including our own, show that new genes can evolve de novo from non-coding sequences and that new portions of genes can also arise in this manner.
The aims of this proposal are: 1) to identify more such cases, 2) to investigate the roles of ordered structure and intrinsic structural disorder in de novo protein-coding innovation, and 3) to examine the structural properties of proteins, or portions of proteins, encoded by new coding sequence. Significant possible outcomes include 1) insights into selection processes that allow new genes to arise, 2) the discovery of novel proteins and an ability to compare their properties to those of highly evolved proteins, yielding insights into the protein folding code and protein design/engineering. The newness of this research area, as well as the incorporation of cutting-edge evolutionary theory and studies of de novo protein structure, make this work highly innovative. The PI team is interdisciplinary and complementary, including both an evolutionary biologist and an experimental structural biologist/biochemist.
Newly evolved genes may be important in the ongoing evolutionary battle between humans and their pathogens, and in other evolutionary arms races important to psychiatric and reproductive disorders. This work will study factors that could make it easier for new genes to evolve, as well as differences and similarities between the structures of newly evolved genes and old genes.
|Stewart, Katie L; Rathore, Deepali; Dodds, Eric D et al. (2018) Increased sequence hydrophobicity reduces conformational specificity: A mutational case study of the Arc repressor protein. Proteins :|
|Kumirov, Vlad K; Dykstra, Emily M; Hall, Branwen M et al. (2018) Multistep mutational transformation of a protein fold through structural intermediates. Protein Sci 27:1767-1779|
|Willis, Sara; Masel, Joanna (2018) Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes. Genetics 210:303-313|
|Wilson, Benjamin A; Foy, Scott G; Neme, Rafik et al. (2017) Young Genes are Highly Disordered as Predicted by the Preadaptation Hypothesis of De Novo Gene Birth. Nat Ecol Evol 1:0146-146|
|Bungard, Dixie; Copple, Jacob S; Yan, Jing et al. (2017) Foldability of a Natural De Novo Evolved Protein. Structure 25:1687-1696.e4|
|Masel, Joanna; Promislow, Daniel E L (2016) Answering evolutionary questions: A guide for mechanistic biologists. Bioessays 38:704-11|
|Andreatta, Matthew E; Levine, Joshua A; Foy, Scott G et al. (2015) The Recent De Novo Origin of Protein C-Termini. Genome Biol Evol 7:1686-701|
|Murren, C J; Auld, J R; Callahan, H et al. (2015) Constraints on the evolution of phenotypic plasticity: limits and costs of phenotype and plasticity. Heredity (Edinb) 115:293-301|
|Teufel, Ashley I; Masel, Joanna; Liberles, David A (2015) What Fraction of Duplicates Observed in Recently Sequenced Genomes Is Segregating and Destined to Fail to Fix? Genome Biol Evol 7:2258-64|
|Trotter, Meredith V; Weissman, Daniel B; Peterson, Grant I et al. (2014) Cryptic genetic variation can make ""irreducible complexity"" a common mode of adaptation in sexual populations. Evolution 68:3357-67|
Showing the most recent 10 out of 11 publications