• Mohor Sengupta

Snails are quick to pick sides.

Updated: Aug 8, 2019

Image source: Wikimedia Commons.

Chirality, or lateral orientation, pervades the biological world. As humans, we have the heart to left side of the body, stomach to the left again and the appendix to the right. But 1 in 10,000 humans are born with a mirror image of this setting, that is, their heart is on the right side of the body. The condition is called situs inversus totalis. Although this condition doesn't affect the person born with it, and before the advent of modern medicine it was undiscovered until someone opened up a cadaver, scientists remain inquisitive about its cause.

Situs inversus. Image source: Wikimedia Commons.

The snail has proven to be a good model organism to understand the biology behind chirality during development, in this case manifested by shell coiling. Chirality in snails has been studied since a long time. Snails mostly coil their shells to the right. If you observe a snail sideways with its anterior tip facing the top, the shell is usually on the right (dextral). However, in some species, rare individuals coil their shell to the left (sinistral). The reversed chirality affects the snail's internal organization as well.

Years ago, the hero of modern genetics Alfred Sturtevant published a paper in which he noted that the sinistral determining genetic factor (let's call it d) is recessive to D, the dextral coiling factor. However, there's a twist here. Only the mother's genetic makeup influences the offspring's chiral preference. That is, if a dd snail mom has babies with a DD snail dad, the kids are sinistral irrespective of their d/D situation. It has taken years for scientists to identify the 'D' gene Sturtevant was talking about in 1923.

In 2016 Dr. Angus Davison and colleagues identified the gene Ldia2 whose mutation causes sinistral coiling in Lymnaea stagnalis, the freshwater snail. At the same time, Dr. Reiko Kuroda and colleagues independently stumbled upon Lsdia1, whose mutation was responsible for sinistral coiling in the same species. A working Lsdia1 gene was necessary and sufficient for dextral coiling; in other words, it was the 'D' sought after for decades.

In a recent publication in the journal 'Development', Kuroda and Dr. Masanori Abe used CRISPR/Cas9 to mutate functional Lsdia1 in L. stagnalis. The mutation produced left-coiled snails in otherwise totally dextral genetic background. This is the first time the popular gene editing technology, CRISPR, has been used in a mollusc.

Another striking revelation from Kuroda's studies is that chirality in the freshwater snail is determined at one-cell stage, "the earliest observed symmetry-breaking event linked directly to body handedness in the animal kingdom".

While the cytoskeletal spindle of a right-handed snail embryo tilts clockwise, causing its cells to twist in a clockwise direction, in absence of the Lsdia1-encoded protein LsDia1, the spindle does not tilt at all. Without this tilt, cells in the developing mutant embryo don't twist. As they divide, they perfectly position themselves radially, and grow up to become a left-coiling snail.

Without working copies of Lsdia1 gene, the left-coiling snails survive for generations compensated by the closely related Lsdia2 gene, which doesn't determine chirality. Lefty snails spend a lifetime looking for lefty mates. However, some, like Jeremy, find their match, thanks to human intervention. Some others manage to mate with a right-coiling partner (it's not easy!).

Dr. Angus Davison, scientist at the University of Nottingham, holding two rare left-coiling snails. These snails were found as a result of worldwide search to find a mate for Jeremy, the lefty garden snail. Source: Wikimedia Commons.