You’ve heard of the “Cambrian Explosion,” right? The Cambrian period is known for its plethora of bizarre animal forms that seemingly exploded out of nowhere. The period began about 541 million years ago (mya) and ended a little under 485 mya. Even though a heck of a lot was happening before this time period, evolutionarily speaking, many of the animals before the Cambrian were primarily soft-bodied and didn’t fossilize often– not like a lot of the later Cambrian fauna with their hard shells and chitin-rich exoskeletons.
But it was also during this period that an unassuming branch of chordates (animals with notochords, like us) were evolving the first vertebral columns and skulls. These were the first fish. And even though their internalized skeletons were made of collagen and didn’t yet contain any calcified hard parts, these early fish had something truly special going on: they were evolving the first brains.
I’ve developed a class on the evolution of the nervous system and in it I teach my students that we vertebrates didn’t have the monopoly on complicated nervous systems. Even animals like jellyfish have nerve nets underlying their “skin” that help coordinate their movements and the lobster you ate at that fancy restaurant last weekend had a nervous system that was centralized, running the length of much of its body and helping to coordinate right and left. In all of these animals, nerves may bundle together to form “ganglia” at key sites in the body in order to do heavier processing of incoming sensory information and outgoing motor movements. What’s more, the vertebrate’s closest cousins on the family tree, the tunicates, have a “cerebral bulge” when they’re tadpole-like larvae (image below)– not quite what you would call a “brain,” but definitely a collection of nerves in the head region.
So, what makes vertebrates so special? Well, not only is our cerebral bulge really huge compared to other animals, it’s divided into three parts: forebrain, midbrain, and hindbrain. That forebrain, in particular, is really important in our lineage because a part of it called the “telencephalon” is something that’s totally unique to all living vertebrates. The telencephalon is the part in humans that takes up most of the space in that gigantic cranium of ours. So, not only were vertebral columns and skulls evolving in early fishes during this fascinating period known as the Cambrian, but we also seemed to be evolving the foundations of the telencephalon, that part of us that is ultimately responsible for our complex memories, emotional experiences, and perception of consciousness.
You may be wondering why I’m waxing eloquent about fishes and what in the world they have to do with autism genetics. It just so happens that my lab has published an article this month in Autism Research reporting that a large minority of major effect autism susceptibility genes evolved during this early time period of vertebrate evolution. What does that mean? Well, it probably means that a lot of these genes are integral to the foundations of the telencephalon and likely played important roles in the expanding complexity of tissues like the cerebral cortex. It may also give us a view behind the curtain, so to speak, allowing us to better understand the functions of these genes from an evolutionary perspective. As I always like to say, understanding how genes and structures evolved gives us vital context as to what they’re doing in our bodies today.
What’s even more interesting to a genetics geek like me, a lot of these genes evolved as a result of two whole genome duplications that occurred during early vertebrate evolution. What do I mean by whole genome duplication? It’s actually exactly like it sounds: Once upon a time, the genome was duplicated, leading not to diploid (two) pairs of chromosomes, but tetraploid (four) pairs. And then it duplicated again, leaving us essentially with eight pairs of chromosomes. After a little while, this eventually reverted to diploid genomes, but with all those extra gene copies. Slowly over time, many of those gene copies were lost, deleted by mutational accident because they just weren’t that important. But a lot of the autism gene copies were kept for reasons that are a little too complicated for this already-complicated blog and eventually many of these copies were tweaked over time, evolving slightly differently from their parent copies. From this, new and interesting functions arose. Most of the time, these duplicates probably continued to do something somewhat similar to their parents but they may have evolved to do so in new types of cells, leading to what we call cell type-specific gene expression. In this way, these new gene copies probably led to new neuron types, new brain regions, and remarkable complexity.
Probably most of us wouldn’t think of a fish as being inherently “smart”– but consider the shark who hunts its prey with stealth and speed, able to smell the slightest whiff of blood over a quarter mile away, and compare him to the house fly banging up against your living room window for hours at a time. You may start to appreciate that intelligence is relative. Think again of the monitor lizards who violently spar for territory, the cockatoos that sing and dance on YouTube videos, or dogs who learn to communicate using talking buttons and once again you may appreciate the incredible impact the telencephalon has had on the evolution of vertebrate behavior.
And buried at the core of that evolution is a group of genes that nowadays, when mutated in humans, dramatically increases the likelihood a person will develop autism.