Details

Autor(en) / Beteiligte

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

Titel

Systematic humanization of yeast genes reveals conserved functions and genetic modularity

Ist Teil von

• Science (American Association for the Advancement of Science), 2015-05, Vol.348 (6237), p.921-925

Ort / Verlag

Washington: American Association for the Advancement of Science

Erscheinungsjahr

2015

Link zum Volltext

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.