SRGAP2 (SLIT-ROBO Rho GTPase activating protein 2)

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What is MOCA?
MOCA FAQ...
Human Uniqueness Compared to "Great Apes": 
Likely Difference
Human Universality: 
Individual Universal (All Individuals Everywhere)
MOCA Domain: 
Genetics
MOCA Topic Authors: 
Majesta O'Bleness
James Sikela

SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) directly regulates membrane deformation for proper neuronal migration and axon-dendrite morphogenesis. The human lineage underwent 3 partial duplication events, of which 1 is fixed and the other two remain polymorphic within the human population. The partial copies act as an inhibitor of the full length SRGAP2 protein, which results in delayed neuronal spine maturation and increased density of the longer spines. These duplication events are hypothesize to have resulted in human specific changes to the neocortex.

Timing

Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Probable Appearance: 
2,000 thousand years ago
Definite Appearance: 
6,000 thousand years ago
Related MOCA Topics
Related Topics (hover over title for reason):
Topic Certainty
Brain Size Speculative
Genetics Topic Attributes
Gene symbols follow the HUGO Gene Nomenclature Committee standard.
Gene Symbol Type of Human-Specific Changes
SRGAP2 Copy Number Changes

References

  1. Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication., Dennis, Megan Y., Nuttle Xander, Sudmant Peter H., Antonacci Francesca, Graves Tina A., Nefedov Mikhail, Rosenfeld Jill A., Sajjadian Saba, Malig Maika, Kotkiewicz Holland, et al. , Cell, 2012 May 11, Volume 149, Issue 4, p.912-22, (2012)
  2. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation., Charrier, Cécile, Joshi Kaumudi, Coutinho-Budd Jaeda, Kim Ji-Eun, Lambert Nelle, de Marchena Jacqueline, Jin Wei-Lin, Vanderhaeghen Pierre, Ghosh Anirvan, Sassa Takayuki, et al. , Cell, 2012 May 11, Volume 149, Issue 4, p.923-35, (2012)
  3. Diversity of human copy number variation and multicopy genes., Sudmant, Peter H., Kitzman Jacob O., Antonacci Francesca, Alkan Can, Malig Maika, Tsalenko Anya, Sampas Nick, Bruhn Laurakay, Shendure Jay, and Eichler Evan E. , Science, 10/2010, Volume 330, Issue 6004, p.641-6, (2010)
  4. The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis., Guerrier, Sabrice, Coutinho-Budd Jaeda, Sassa Takayuki, Gresset Aurélie, Jordan Nicole Vincent, Chen Keng, Jin Wei-Lin, Frost Adam, and Polleux Franck , Cell, 2009 Sep 4, Volume 138, Issue 5, p.990-1004, (2009)
  5. Lineage-specific gene duplication and loss in human and great ape evolution., Fortna, A., Kim Y., MacLaren E., Marshall K., Hahn G., Meltesen L., Brenton M., Hink R., Burgers S., Hernandez-Boussard T., et al. , PLoS Biol, 07/2004, Volume 2, Issue 7, p.E207, (2004)

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