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Tuesday, May 8, 2012

If you can understand this, thank a DNA replication error.

Our DNA replication machinery is remarkably accurate and efficient, but errors do occasionally occur. For example, the same gene may be replicated more than once, resulting in multiple copies of that gene. According to Evan Eichler and his colleagues from the University of Washington and other institutions, one such duplication event may have been responsible for the differences between our brains and those of the great apes.

The original gene, SRGAP2, encodes a protein that is critical for neuronal development in mammalian embryos. Around the time Australopithecus was evolving into Homo, we ended up with a couple of extra copies of this gene. Chimps and orangutans each have only one version of the gene, but we have four. The first duplication (SRGAP2B) probably occurred about 3.4 million years ago (mya), the next (SRGAP2C, a copy of SRGAP2B), 2.4 mya, and the last (SRGAP2D, also a copy of SRGAP2B) only 1 mya.

Upon reading that humans have extra copies of a gene involved in neuron maturation, you might think that it’s the excess amounts of this protein product that lets us be so brainy. Not so. Franck Polleux of the Scripps Research Institute and his colleagues found that the second SRGAP2 duplication (SRGAP2C) encodes a protein that actually interferes with the original gene product. To operate properly, two SRGAP2 proteins must combine together. Because SRGAP2C encodes an incomplete copy, it can pair with the original SRGAP2, but the result is unusable. In other words, thanks to the duplication events, we have less functional SRGAP2 protein, not more. 

The consequence of this is that the developmental schedule of neurons is altered. With SRGAP2 blocked during embryogenesis, the period of time allowed for neuronal development is elongated. This allows for the formation of longer and more numerous neuronal spines, the parts of the neuron that make connections with other neurons. SRGAP2 also inhibits neural migration, the spreading of neurons throughout the brain. Without it, neurons can continue to migrate for longer. It’s not difficult to see how these changes would have had a huge impact on the evolution of hominin brains.

Think about this: not only were there errors in replicating SRGAP2 millions of years ago, but those errors resulted in a protein product that exactly interfered with the original product. We may very well owe our ability to reason to those serendipitous events. You gotta love evolution.