Our left and right sides are largely mirror images of each other. That makes us bilaterians, a large group of animals that range from tiny flies to giant whales. But we and the whales share a significant difference with flies—where we put our nerve cord. For us, the spinal cord runs down our back. For flies and other insects, the primary nerve cord is on the underside of the animal.

This wouldn't be that surprising if the two nerve cords had distinct origins, but we've discovered that all the molecules that place and pattern the nerve cord are similar in insects and vertebrates. That suggests the nerve cord has always been in the same place; instead, the rest of the body somehow ended up flipped relative to the nerves. Now, the genome of a strange animal called the acorn worm may help us sort out how that could have happened.

One possible hypothesis for how the nerve cord flipped is that the ancestor of us vertebrates lived as a burrowing animal in a marine environment. There, such an ancestor might not need any top/bottom axis and could have lost it. Once its descendants re-emerged from the mud, they re-established this axis but did it in the opposite orientation.

If this hypothesis is accurate, then you might expect the descendants of these burrowing animals to still be around—a worm that's closely related to vertebrates. And that's just what the acorn worms are. These strange animals have a strange body plan with a proboscis in front, followed by a thick collar and then a long tubular body. There is no obvious top or bottom to it. Disturbingly, the larger species can get up to a meter-and-a-half long.



Are acorn worms our long-lost relatives? Well, it's complicated. To begin with, their collar doesn't have a nerve cord at all but rather a diffuse net. Further down the body, there are two nerve cords on opposite sides of the body. This looks like a great candidate for an axis-flipping intermediate.

But both we and they are part of a larger group called deuterostomes, and pretty much any of these could be a plausible bridge between vertebrates and the rest of the animals. These also include things that are obviously related to us, like the lancelet (amphioxus), an animal with a simple nerve cord. But oddly, they're not our closest relatives. That honor belongs to a group of organisms that includes sea squirts. These spend most of their life attached to rocks with little in the way of a body plan we'd view as familiar. However, their larval stage looks a lot more like a tadpole—complete with a nerve cord on its back.

Elsewhere in the group, we have the echinoderms like starfish and sea urchins. These organisms are famously radially symmetric in appearance. But that appearance hides what are some clear axes internally, some of which are even more obvious in the larval stages. Finally, on the periphery of the group are some truly bizarre creatures like xenoturbella.

Figuring out how they're all precisely related has been difficult, but genome sequencing is gradually helping sort that out. It's what placed the sea squirts between us and the lancelet, meaning they're ruled out as the transition to a nerve cord on our backs. So, what do the acorn worm genomes tell us?

The authors of the new paper sequenced the genomes of two different species. Both of them had about 19,000 obvious genes—roughly the same as humans. The authors found that they had a lot of the gene organization of other animals in this group, including us and echinoderms (introns in the same places and so on). They even identified a cluster of genes that were organized similarly throughout the group, so they're clearly one of us, if "us" is all the deuterostomes.

(The authors also found that the whole group has picked up a bunch of genes from marine microbes, like single-celled algae, which provides support for the idea that our ancestors lived in a marine environment.)

The sequence also makes clear that these worms are most closely related to echinoderms like the sea urchin. That group forms a sister group to everything with a nerve cord on its back.

That's still consistent with our ancestors having been organisms without an obvious top or bottom, but it expands it out a bit, suggesting that this is true for every animal within the deuterostomes—the entire group, including echinoderms and sea squirts.

To know more, we actually have to get into the timing of when specific groups branched off. And that's really hard given that the authors' molecular clock estimates place this all the way back in the Cambrian. It may take many more genomes to sort this one out.

Disclosure: I took a graduate seminar from one of the authors of this paper. He gave me a decent grade even though I was heavily drugged due to knee surgery for most of that semester.

Nature, 2015. DOI: 10.1038/nature16150 (About DOIs).