Title |
Systematic humanization of yeast genes reveals conserved functions and genetic modularity
|
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Published in |
Science, May 2015
|
DOI | 10.1126/science.aaa0769 |
Pubmed ID | |
Authors |
Aashiq H Kachroo, Jon M Laurent, Christopher M Yellman, Austin G Meyer, Claus O Wilke, Edward M Marcotte |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 47 | 20% |
Japan | 36 | 15% |
United Kingdom | 13 | 6% |
Canada | 4 | 2% |
Germany | 4 | 2% |
France | 3 | 1% |
Switzerland | 3 | 1% |
Taiwan | 3 | 1% |
Netherlands | 2 | <1% |
Other | 10 | 4% |
Unknown | 111 | 47% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 158 | 67% |
Scientists | 74 | 31% |
Practitioners (doctors, other healthcare professionals) | 2 | <1% |
Science communicators (journalists, bloggers, editors) | 1 | <1% |
Unknown | 1 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 13 | 2% |
United Kingdom | 5 | <1% |
Canada | 3 | <1% |
Brazil | 2 | <1% |
Italy | 2 | <1% |
Russia | 2 | <1% |
Spain | 2 | <1% |
Korea, Republic of | 2 | <1% |
South Africa | 1 | <1% |
Other | 8 | 1% |
Unknown | 680 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 188 | 26% |
Researcher | 129 | 18% |
Student > Bachelor | 86 | 12% |
Student > Master | 66 | 9% |
Student > Doctoral Student | 41 | 6% |
Other | 108 | 15% |
Unknown | 102 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 266 | 37% |
Biochemistry, Genetics and Molecular Biology | 244 | 34% |
Chemistry | 15 | 2% |
Medicine and Dentistry | 14 | 2% |
Engineering | 11 | 2% |
Other | 52 | 7% |
Unknown | 118 | 16% |