The long-term objective of my research program is to understand the molecular genetic mechanisms and driving forces of phenotypic variation and evolution. Antagonistic pleiotropy (AP) is one of the most common yet least understood phenomena in genetics. It refers to the observation that the phenotypic effects of a mutation on multiple traits are opposite. AP is widely invoked in explanations and models of senescence, cancer, genetic disease, sexual conflict, cooperation, evolutionary constraint, adaptation, neofunctionalization, and speciation. For instance, a prevailing theory of aging asserts that mutations beneficial to development and reproduction in early stages of life tend to be deleterious later in life and cause senescence. AP is also believed to cause the unexpected prevalence of some genetic diseases, due to the benefits conferred by the disease-causing mutations to other aspects of life. For instance, mutations causing Huntington's disease are known to increase fecundity. AP dictates that a mutation is unlikely to be advantageous to multiple traits or in multiple environments, leading to compromises among adaptations of different traits or in different environments. This fundamental property limits the extent and rate of adaptation and guarantees that no species or genotype would outperform all others in all environments. In contrast to the importance of AP in many theories as well as human health issues, our empirical knowledge and understanding of AP is extremely limited. It is unknown (i) how prevalent AP is at the genomic scale, (ii) what genes tend to be subject to AP and under what conditions, and (iii) whether, to what extent, and by what genetic mechanisms AP can be evolutionarily resolved. Three studies, involving functional genomics, molecular genetics, and theoretical population genetics, are proposed to address the above questions at the genomic scale using the baker's yeast Saccharomyces cerevisiae as a model. This project represents the first genome-wide characterization of AP and is expected to expand substantially our knowledge of the patterns and mechanisms of AP. Such knowledge is critically needed for evaluating the validity of all AP-dependent theories and for understanding and solving AP-related health issues.

Public Health Relevance

Although antagonistic pleiotropy (AP) is commonly invoked in explanations of aging, cancer, and genetic disease, there is little empirical knowledge about AP. The proposed work characterizes and clarifies the prevalence of AP, extent and mechanisms of AP resolution, and conditions for AP resolution, providing important information for understanding the proximate and ultimate causes of many diseases and biomedical phenomena.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Krasnewich, Donna M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
Zip Code
Zou, Zhengting; Zhang, Jianzhi (2016) Morphological and molecular convergences in mammalian phylogenetics. Nat Commun 7:12758
Xu, Jinrui; Zhang, Jianzhi (2016) Are Human Translated Pseudogenes Functional? Mol Biol Evol 33:755-60
Xu, Jinrui; Zhang, Jianzhi (2016) Impact of structure space continuity on protein fold classification. Sci Rep 6:23263
Chen, Xiaoshu; Zhang, Jianzhi (2016) The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells. Mol Biol Evol 33:3104-3107
Li, Chuan; Qian, Wenfeng; Maclean, Calum J et al. (2016) The fitness landscape of a tRNA gene. Science 352:837-40
Ho, Wei-Chin; Zhang, Jianzhi (2016) Adaptive Genetic Robustness of Escherichia coli Metabolic Fluxes. Mol Biol Evol 33:1164-76
Moyers, Bryan A; Zhang, Jianzhi (2016) Evaluating Phylostratigraphic Evidence for Widespread De Novo Gene Birth in Genome Evolution. Mol Biol Evol 33:1245-56
Chen, Xiaoshu; Yang, Jian-Rong; Zhang, Jianzhi (2016) Nascent RNA folding mitigates transcription-associated mutagenesis. Genome Res 26:50-9
Chen, Xiaoshu; Zhang, Jianzhi (2016) The Genomic Landscape of Position Effects on Protein Expression Level and Noise in Yeast. Cell Syst 2:347-54
Moyers, Bryan A; Zhang, Jianzhi (2015) Phylostratigraphic bias creates spurious patterns of genome evolution. Mol Biol Evol 32:258-67

Showing the most recent 10 out of 26 publications