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Systematic humanization of yeast genes reveals conserved functions and genetic modularity

Kachroo, Aashiq H. ; Laurent, Jon M. ; Yellman, Christopher M. ; Meyer, Austin G. ; Wilke, Claus O. ; Marcotte, Edward M.

Science (American Association for the Advancement of Science), 2015-05, Vol.348 (6237), p.921-925 [Periódico revisado por pares]

Washington: American Association for the Advancement of Science

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  • Título:
    Systematic humanization of yeast genes reveals conserved functions and genetic modularity
  • Autor: Kachroo, Aashiq H. ; Laurent, Jon M. ; Yellman, Christopher M. ; Meyer, Austin G. ; Wilke, Claus O. ; Marcotte, Edward M.
  • Assuntos: Biological evolution ; Divergence ; Evolutionary ; Gene expression ; Gene sequencing ; Genes ; Genetics ; Proteins ; Similarity ; Simulation ; Yeast
  • É parte de: Science (American Association for the Advancement of Science), 2015-05, Vol.348 (6237), p.921-925
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: To determine whether genes retain ancestral functions over a billion years of evolution and to identify principles of deep evolutionary divergence, we replaced 414 essential yeast genes with their human orthologs, assaying for complementation of lethal growth defects upon loss of the yeast genes. Nearly half (47%) of the yeast genes could be successfully humanized. Sequence similarity and expression only partly predicted replaceability. Instead, replaceability depended strongly on gene modules: Genes in the same process tended to be similarly replaceable (e.g., sterol biosynthesis) or not (e.g., DNA replication initiation). Simulations confirmed that selection for specific function can maintain replaceability despite extensive sequence divergence. Critical ancestral functions of many essential genes are thus retained in a pathway-specific manner, resilient to drift in sequences, splicing, and protein interfaces.
  • Editor: Washington: American Association for the Advancement of Science
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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