Systematic Humanization of the Yeast Cytoskeleton Discerns Functionally Replaceable from Divergent Human Genes.

Genetics
Riddhiman K GargeEdward M Marcotte

Abstract

Many gene families have been expanded by gene duplications along the human lineage, relative to ancestral opisthokonts, but the extent to which the duplicated genes function similarly is understudied. Here, we focused on structural cytoskeletal genes involved in critical cellular processes, including chromosome segregation, macromolecular transport, and cell shape maintenance. To determine functional redundancy and divergence of duplicated human genes, we systematically humanized the yeast actin, myosin, tubulin, and septin genes, testing ∼81% of human cytoskeletal genes across seven gene families for their ability to complement a growth defect induced by inactivation or deletion of the corresponding yeast ortholog. In five of seven families-all but α-tubulin and light myosin, we found at least one human gene capable of complementing loss of the yeast gene. Despite rescuing growth defects, we observed differential abilities of human genes to rescue cell morphology, meiosis, and mating defects. By comparing phenotypes of humanized strains with deletion phenotypes of their interaction partners, we identify instances of human genes in the actin and septin families capable of carrying out essential functions, but failing to fully c...Continue Reading

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Citations

Feb 10, 2021·G3 : Genes - Genomes - Genetics·Julie TakagiGregory C Finnigan
Jul 24, 2021·Trends in Genetics : TIG·Elena KuzminCharles Boone

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Methods Mentioned

BETA
phylogenetic profiling
dissection
dissections
PCR
environmental stress

Software Mentioned

Rstudio
RAxML
ggplot2
ImageJ
Zeiss ZEN Microscope
Geneious
GraphPad Prism
FIJI
InParanoid
ggridges

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