Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection
Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals...
| Հիմնական հեղինակներ: | , , , |
|---|---|
| Ձևաչափ: | Journal article |
| Լեզու: | English |
| Հրապարակվել է: |
Public Library of Science
2008
|
| _version_ | 1826297178745733120 |
|---|---|
| author | Rosso, L Marques, A Reichert, A Kaessmann, H |
| author_facet | Rosso, L Marques, A Reichert, A Kaessmann, H |
| author_sort | Rosso, L |
| collection | OXFORD |
| description | Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor approximately 18-25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions. |
| first_indexed | 2024-03-07T04:27:37Z |
| format | Journal article |
| id | oxford-uuid:cd323d0d-edea-4c16-815e-c8f0a55812eb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:27:37Z |
| publishDate | 2008 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:cd323d0d-edea-4c16-815e-c8f0a55812eb2022-03-27T07:27:00ZMitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cd323d0d-edea-4c16-815e-c8f0a55812ebEnglishSymplectic Elements at OxfordPublic Library of Science2008Rosso, LMarques, AReichert, AKaessmann, HMany new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor approximately 18-25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions. |
| spellingShingle | Rosso, L Marques, A Reichert, A Kaessmann, H Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection |
| title | Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection |
| title_full | Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection |
| title_fullStr | Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection |
| title_full_unstemmed | Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection |
| title_short | Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection |
| title_sort | mitochondrial targeting adaptation of the hominoid specific glutamate dehydrogenase driven by positive darwinian selection |
| work_keys_str_mv | AT rossol mitochondrialtargetingadaptationofthehominoidspecificglutamatedehydrogenasedrivenbypositivedarwinianselection AT marquesa mitochondrialtargetingadaptationofthehominoidspecificglutamatedehydrogenasedrivenbypositivedarwinianselection AT reicherta mitochondrialtargetingadaptationofthehominoidspecificglutamatedehydrogenasedrivenbypositivedarwinianselection AT kaessmannh mitochondrialtargetingadaptationofthehominoidspecificglutamatedehydrogenasedrivenbypositivedarwinianselection |