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The sources of symmetry

On the outside, we are symmetrical. We each have two eyes, two ears, two arms, and two legs, one each on each side of the body. Unpaired parts of our anatomies - our noses and mouths - are placed straight down the middle.

On the inside, it?s a different story. Our hearts are on the left, but our livers are on the right. Many other internal organs are asymmetrically placed, or, if central, have their own characteristic asymmetries.

What causes this internal asymmetry? More fundamentally, why are we symmetrical on the outside, but asymmetrical on the inside?

Answers to the first question are starting to emerge, thanks to research into a condition called situs inversus viscerum (or just ?situs?) in which the layout of the internal organs is disturbed. A report in 6 August 1998 issue of Nature from Juan Carlos Izpisúaa Belmonte of the Salk Institute in La Jolla, California and colleagues identifies a gene, called Pitx2, that is central in directing internal asymmetry in early embryos.

Some people have a condition called ?dextrocardia?, in which the heart is placed on the right, rather than on the left. This condition may be accompanied by a mirror-image switch in the rest of the viscera, so that (for example) the liver will be on the left, rather than on the right. This is usually quite innocent, and the affected person may be unaware of it until a doctor examines him or her with a stethoscope. The wholesale mirror-image swap of the viscera has no adverse effects. Even though the organs are displaced relative to the situation in most other people, they maintain the correct mutual relations in the affected person, and everything is fine. More of a worry is the occasional case in which the internal organs are not placed consistently one way or the other, but arranged more randomly. This creates obvious problems for internal plumbing, and comes to medical attention. People with this condition, situs ambiguus, may have midline livers, lack the spleen, and have complicated heart defects. Situs is also a complication often associated with conjoined or ?Siamese? twins.

Situs sometimes runs in families. This has prompted researchers to look for genes, in humans and a variety of animals, that regulate the development of asymmetry - genes which, if disrupted, may lead to situs. Several genes have been found which are involved in symmetry to a greater or lesser extent. The emerging picture is of a ?cascade? or ?chain? of genes, each one acting to regulate the action of the next one in the sequence. Most of the genes found so far seem to be active extremely early in embryonic life, even before asymmetry becomes evident in the developing animal. This suggests that further genes, far down the chain of command and more directly involved in symmetry regulation, remain to be discovered. Pitx2 seems to be one of these genes. Regulated by genes higher up the chain, Pitx2 seems to be directly involved in the formation and maintenance of asymmetry.

In the chick, Pitx2 is ?switched on? (or ?expressed?) in tissues destined to become the heart and internal organs, but only on the left side of the animal. Later on, once internal asymmetry is established, it is expressed - symmetrically - in the tissues destined to become the body?s outer musculature, and in the limbs. The picture is very similar in other laboratory animals such as mice and frogs, and it is probably the same in humans, too. The researchers determined that the activity of Pitx2 is controlled by genes higher up the chain - genes with names such as nodal and sonic hedgehog - and that it is the closest thing yet discovered to being the gene most directly responsible for regulating left-right asymmetry. Indeed, Pitx2 seems to have the same role throughout the vertebrates, suggesting that tight regulation of the process has been conserved in evolution.

This finding begs the question posed above: why should we be symmetrical on the outside but not on the inside? Wouldn?t life be easier if we were symmetrical throughout? If so, we wouldn?t need this elaborate chain of genetic command that not only creates asymmetry, but ensures that it is just the right kind of asymmetry, with all the internal organs in a proper, functional relationship with one another. And if asymmetry is possible, and controllable, why aren?t we asymmetrical throughout, on the outside as well as on the inside?

Evolutionary biologists have been interested in external asymmetry as a measure of genetic ?quality?. It seems that animals choose their mates partly on the basis of symmetry. The rationale is as follows: tight control of symmetry is an external measure of orderly genetic control of development. Animals seeking to maximize their genetic contribution to the next generation naturally seek mates in prime genetic health. The more symmetrical a potential mate, the better genes he will have, and the better prospects he will have as a father. (I use the term ?he? deliberately: as females tend to invest more time and effort in family life than males, they generally get to do the choosing.) Researchers have shown, for example, that female barn-swallows (Hirundo rustica) tend to prefer males whose paired tail-forks are of similar lengths.

The argument may extend to humans, too. Everywhere, symmetry is seen as a sign of desirability, beauty and health. Could the wickedness of traditional melodrama villains be increased by such asymmetrical props as an eye-patch or a wooden leg? Perhaps: but in a paper in Nature in 1994, provocatively entitled ?Symmetry, beauty and evolution?, Magnus Enquist of the University of Stockholm, Sweden, and British-based engineer Anthony Arak proposed that symmetry was initially favoured in evolution, simply because symmetrical objects are simpler to recognize from a variety of viewing angles than asymmetrical ones. Our vision-driven brains have learned to recognize symmetry as something special, and this may have been exploited in mate choice - as well as in human art and aesthetics.

All this could explain why animals tend to be symmetrical on the outside. What happens inside is less important, because it is, literally, out of sight. Functionality is a more important consideration than beauty as regards the arrangement of the internal organs, and it could be that the most efficient and compact way of arranging the viscera happens to be asymmetrical.

But there could be an even deeper reason for internal asymmetry. According to one British palaeontologist, Richard Jefferies of the Natural History Museum in London, the tightly regulated asymmetry of vertebrates all started as a symmetry-shattering accident. This misfortune befell a symmetrical creature living on a long-vanished ocean floor, perhaps more than 600 million years ago. This animal was the ancestor of the vertebrates. The subsequent story of vertebrate evolution has been one of a struggle to regain symmetry, a struggle that has been only partially successful. The asymmetry of the internal organs within a symmetrical exterior represents this half-billion-year legacy.

For more than 30 years, Jefferies has been studying an obscure, long-extinct group of creatures called carpoids. These fossil creatures, rarely more than a few centimetres long, have long, spiny ?tails? and blobby, potato-like heads, which are more or less covered with spines and other excrescences. The carpoid body was supported by a skeleton of calcitic plates, exactly like those found in modern echinoderms - starfishes and their relatives - and so carpoids are usually classed with echinoderms.

Jefferies has presented a detailed argument suggesting that the common ancestor of echinoderms and vertebrates would have been a carpoid. This is not quite as outlandish as it may seem, because echinoderms and vertebrates - surprisingly - share many features of their early embryonic development not seen in other animals, and most zoologists mark this as a sign of close common ancestry.

The important thing here is that carpoids differ from all other animals, living and extinct, including echinoderms, in that many of them are completely asymmetrical, inside and outside.

Jefferies has interpreted this asymmetry in a particular way. He suggests that the common ancestor of echinoderms and vertebrates evolved from a symmetrical animal which - for some unknown reason - adopted a lopsided habit, in which all the structures on the right-hand side became suppressed. The animal was not so much asymmetrical, but represented a body-plan in which left-side structures predominated over right-hand structures. (If this sounds far-fetched, one can see a similar phenomenon in flatfishes such as the plaice, in which the body has become rotated by a quarter-turn, and both eyes are effectively on the same side of the animal.)

The descendants of this unfortunate creature were carpoids in which a body consisting, essentially, of the left-hand-side of one animal was reshaped into a symmetrical animal. The results, eventually, were echinoderms and vertebrates. In support of this idea, Jefferies points to pronounced and otherwise inexplicable asymmetries in the development of starfishes, and also in a closer relative of vertebrates, a small fish-like creature called the amphioxus (Branchiostoma). These asymmetries contrast with the more-or-less thoroughly symmetrical bodies of most animals, such as insects and worms (though the spiralling shells of molluscs present an exception.)

Interestingly, this process of symmetry loss afflicted the parts of the carpoid body which, in vertebrates, are cognate with the internal organs. Those parts of the carpoid body which Jefferies envisions as corresponding with the external parts of modern vertebrates largely remained unaffected. This could, in part, explain why modern vertebrates look symmetrical on the outside, but asymmetrical within.

It has to be said that Jefferies?s vision of vertebrate origins is not widely accepted. Yet it seems consistent with the genetic evidence - and it, at least, attempts to provide answers to the intriguing question of the origin of asymmetry.

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Gee, H. The sources of symmetry. Nature (1998). https://doi.org/10.1038/news980806-7

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