Evolutionary decomposition of genetic effects [article]

Li Liu, Mengdi Liu, Di Zhang, Shanjun Deng, Piaopiao Chen, Jing Yang, Yunhan Xie, Xionglei He
2019 bioRxiv   pre-print
Genetics has long been confused by the pleiotropic mutational effects associated with even clearly-annotated genes. To understand such genetic effects, we here examine HAP4, a well-studied transcription factor in Saccharomyces cerevisiae that forms a tetramer with HAP2, HAP3, and HAP5. Deletion of HAP4 results in highly pleiotropic gene expression responses, some of which are clustered in related cellular processes (clustered effects) while most are distributed randomly across diverse cellular
more » ... s diverse cellular processes (distributed effects). The clustered effects tend to be conserved in related yeasts while the distributed effects, which account for the pleiotropy of HAP4, are genetically non-heritable and evolutionarily volatile. There are substantial overlaps among clustered effects, but not distributed effects, of the four genes encoding the HAP2/3/4/5 tetramer, and this pattern holds for other biochemically characterized protein complexes and KEGG pathways. We further examine a large set of cell morphological traits of the gene deletion lines and obtain consistent results. Hence, an expanded framework for reverse genetics is suggested, in which genetic effects are further divided into evolutionarily selected and unselected ones, with the former supporting related biochemistry understandings and the latter accounting for cryptic pleiotropy.
doi:10.1101/688358 fatcat:jo43lzdqbzckfaqxzykt72hqzm