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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM104040-01A1
Application #
8577353
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2013-08-19
Project End
2017-06-30
Budget Start
2013-08-19
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$234,172
Indirect Cost
$63,172
Name
University of Arizona
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
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