September 20, 2021

I, Science

The science magazine of Imperial College

A ‘double’ variation of the household flower, Busy Lizzy (Impatiens wallenaria) caused by a homeotic mutation

Picking up a penny won’t make you an instant millionaire. But what if it was the penny that made up the exact price of a lottery ticket you were going to buy, and that ticket won you the lottery, and hence made you a millionaire?

Small and singular changes can result in massive consequences. However, as the situation above exhibits, these occurrences can be few and far between. Although, when it does happen, it certainly happens.

Single gene mutations have displayed some of the most remarkable physical changes in humans, insects and plants. It is largely uncommon to see such a dramatic change as a result of a single mutation of a gene.

However, research from the Yale School of Medicine released this week has shown that a single gene, namely laminin gamma3 (LAMC3), determines the characteristic folding of the brain’s cerebral cortex.  A patient who had two base pair deletions within LAMC3 displayed a smooth unfolded conformation of the brain.

Folding of the brain is found in higher mammals, i.e. those with larger brains. This elite includes apes, dolphins and us. Less advanced, and arguably less evolved, mammals possess similar unfolded brain structures to that of the patient above. These creases of the brain are thought to be an evolved strategy to increase surface area of the cerebral cortex within the circumferential limitations of the skull. An advance on surface area allowed more complex thought and reasoning. It’s now possible to theorise that mutations in the gene now labeled LAMC3 allowed the advent of more intelligent forms of life, and further along the line, us.

A Hox mutation is thought to be responsible for this terrifying snake with a leg. Don’t worry, an old Chinese woman batted it to death with a spade.

Some single gene mutations, those of the so called ‘homeotic’ variety, provide us with some of the most astounding morphological alterations. Homeotic mutants possess entire limbs or organs which abnormally replace what was meant to be there in the first place.

The phenomenon of homeosis was first discovered as far back as 1894 when British geneticist William Bateson noticed extra stamens growing in place of entire petals on natural flower mutant varieties. Such a dramatic change in floral organ structure led Bateson to believe these natural variations were distinct from the mechanisms of evolution proposed by Charles Darwin in the Origin of Species. Of course, he turned out to be wrong.

Floral homeosis has been harnessed for horticultural purposes. ‘Double’ flowers are cultivated when natural variants possessing extra petals in place of stamens are purposefully selected for. We’ve always had a keen eye for homeotic variants in nature. The Ancient Chinese were known to be selecting double variants of peonies around 750AD and the China Rose, Rosa chinensis, was bred from naturally-occurring double mutants. The more petals, the more pleasing to the eye; the majority of cultivated rose varieties exhibit some form of homeosis upon wild variants.

Imagine having an extra leg on your face. This unfortunate fly didn’t have to.

Perhaps the most disturbing examples of homeotic mutations are from studies on the fruit fly, Drosophila melongaster.  The body composition of the fruit fly is determined by homeotic genes, or Hox (Homeobox) genes; Hox mutant organisms can exhibit devastating physical defects. Flies with a defective Ubx (Ultrabithorax) gene develop a redundant second set of wings. Another terrifying but strangely intriguing  Hox mutant of the fruit fly has a leg in place of an antennae. An extra limb on your face is interesting by any means.

Hox mutations in humans result in synpolydactyly, characterised by an extra finger between the third and fourth. These three digits are often poorly separated in development and can also be fused.

Homeotic genes are another example of how wondrous the nature of our genetic make-up is. Such a small genetic alteration creating a largely uncorrelated physical change has almost allowed the otherwise gradual process of evolution to leapfrog itself. Homeosis is the underlying mechanism behind instantly different and wildly varying iterations of previous ‘normal’ formations in plants, insects and animals. Whether mutants in these linchpin genes are fatal to the organism or not, the genes still exist across different kingdoms of biology.  Their presence is as beneficial, in the case of human evolution and horticultural breeding, as it is disturbing and sometimes fatal when things go wrong.