Just over 100 years ago, in 1911, Frederick Gudernach, a graduate student at the Medical School in Munich and future renowned American biologist, fed tadpoles with various animal tissues. This simple laboratory study, which today would be suitable for school biology classes, brought a startling discovery. Having eaten fragments of horse thyroid gland, the larvae suddenly began to rapidly metamorphose, that is, to turn into adult frogs. It was from this moment it became clear that the thyroid hormone secreted by the thyroid gland is a powerful stimulator of development, and then biological science decided to look at both the hormone and the gland as closely as possible. It is difficult to name the functions of the body that do not depend on the thyroid gland. Even stress is not without its “help”. Thyroid hormone is involved in mechanisms that increase the permeability of cell membranes, which allows the transfer of stress hormones such as adrenaline or noradrenaline inside the cells. Thyroid hormone regulates both the growth and development of the gonads.

For humans, changes in thyroid function almost always cause disease. Almost half of the world’s population is adversely affected by either a deficiency of thyroid hormone, thyroid hormone, or an excess of it. And most importantly, this hormone has a multifaceted effect. It affects growth, the formation of musculoskeletal, nervous and digestive systems, metabolism, maintenance of body temperature, etc. Lack of thyroid hormone in the early stages of human development often leads to cretinism: stunted growth, dementia and speech difficulties. Thyroid hormone contains iodine, and so the most serious problems associated with deficiency of the hormone have been observed where iodine is deficient. This is not always the case in environmentally deprived areas – in the recent past the term “alpine cretinism” has been in common use. In some areas of the Alps, as it turns out, the water is so pure that its iodine content is close to zero. The result is a high incidence of cretinism in the local population. The problem was solved by including iodised salt in the diet of people living in these areas.

But thyroid hormone plays an even more important role in the development of cold-blooded vertebrates, particularly fish and amphibians. And especially those whose ontogenesis includes the stage of metamorphosis – transformation from larval to mature form. The article “Underdeveloped pioneers” (“PM” № 9’2012) spoke in detail about the phenomenon of neoteny. In neoteny the child (juvenile), often larval form of a living being never acquires the appearance of an adult, but continues to grow and reaches sexual maturity. So, it turns out that one of the decisive factors for the occurrence of neoteny is a reduced level of thyroid hormone. A flounder larva looks like a normal fish larva. And only after metamorphosis, the fish turns on its side and lies on the bottom, changing the type of food, and the eye from the side facing the bottom, “moves” to the opposite side. However, the Japanese, breeding flounder on farms, once noticed that among the adult fish are individuals who have retained larval features: and they swim in the water column, not lying on the bottom on their side, and the eyes in the standard place, and predatory habits of flounder are absent. “Wrong” flounders were also caught in the open sea. All these adult larvae have one thing in common: they have not passed the stage of metamorphosis as a result of thyroid gland dysfunctions.

According to one hypothesis, Neanderthals also had thyroid problems. In the structure of their bodies there are some features characteristic of modern people suffering from cretinism: similar bone structure, curvaceous body, short lower limbs. The decisive role of thyroid hormone in the development of organisms makes us remember the theory of the German-American biologist Richard Goldschmidt, who considered macroevolutionary changes as a consequence of a single mutation affecting the work of endocrine glands and causing coordinated changes in the morphology of the organism, rather than the result of a gradual accumulation of small evolutionary changes. These could include mutations related to the production of thyroid hormone, or more precisely, to the entire thyroid axis.

The existence of the species flock phenomenon indicates that evolution, at least at times, has been explosive. For a long time it was believed that the most probable mechanism of speciation was allopatry – the division of the range of the ancestral species into several parts, leading to reproductive isolation of populations. Sympatric speciation (formation of several species from populations not separated by geographical barriers) remained hypothetical for a long time. Suddenly, one after another, “species bundles” began to be discovered. Among the best known are bundles of 200 and 500 species of cichlids from the African Great Lakes: Tanganyika and Victoria. In each, many genetically closely related species of fish have been found, presumably descended from a single ancestor. These fish, however, are so different from each other that they can be classified not only as different species, but also as different genera. Often the lakes in which “bundles” are formed have a very short geological history, which indicates that speciation was rapid and explosive. Is there no trace of thyroid hormone in such a rapid evolution?

To confirm or refute this hypothesis, the authors of this article are conducting research as part of a joint Russian-Ethiopian biological expedition on the shores of Lake Tana, the largest lake in Ethiopia. In its waters, perhaps one of the most famous “species bundle” of carp fishes, consisting of 15 species of large African whiskers, well differentiated by morphology, lifestyle, behaviour and type of feeding, has arisen. More than half of these species are active predators, which is highly atypical for carps, because they have no jaw teeth, only pharyngeal teeth. Moreover, among the predators there are huge fish, while the parental form is quite small. Lake Tana has dried up more than once in its history and was last filled with water 15,000 years ago. So all this diversity, both morphological and behavioural, has occurred in a time frame that, by evolutionary standards, is comparable to fractions of a second. The hypothalamus is the part of the intermediate brain that controls the endocrine system. It also records all changes that occur in the blood and cerebrospinal fluid.

The first step in the study was to obtain fertilised eggs from ancestral fish. Most species of Tanae roach spawn in rivers flowing into the lake, travelling quite far upstream (50–70 km), where they look for small rapids with a bottom covered with fine gravel, clean and oxygen-rich water, and a fast current. Bearded carp spawn mainly at night, which makes it difficult to catch a spawning group, i.e. females and males of the same species that are ready to reproduce. If such a group is found, it is caught with a cast net. The eggs are squeezed out of the female into a special Petri dish with high mesh sides, and sperm from one of the males is added nearby. The sperm and eggs are then carefully mixed and washed with river water. Fertilised sturgeon eggs are highly adhesive and instantly stick to the bottom and sides of the Petri dish. When the eggs begin to detach from the bottom and sides of the dish, they are carefully transferred to a plastic bottle with river water and transported to the laboratory (sometimes more than 100 km away), where the larvae and young catfish are then grown. In the laboratory, the eggs are divided into groups: a control group, grown in clean water; a group grown in conditions of hyperthyroidism — with an increased concentration of thyroid hormone (for this, the active form of the hormone is added directly to the water); and a group kept in conditions of hypothyroidism or thyroid hormone deficiency (for this, goitrogen, a substance that suppresses the activity of the thyroid gland, is added to the water). Fish species and even genera differ in several important characteristics: the number of scales, pharyngeal teeth, bones, fin rays, etc. It was found that a change in the level of thyroid hormone causes a change in the number of these structures. The characteristics used to distinguish between species of Tansky barbels are the shape and proportions of the head and body. It turned out that at high hormone levels, their snouts become shorter (a distinctive feature of one of the species). When the hormone concentration was reduced, the fish became more similar to some species of predatory barbels than to their parents, which were omnivorous. Another example. In the back of fish, above the spine between the head and the dorsal fin, there are bones called supraneuralia. Ancient fish had many such bones, but in modern carp, their number has greatly decreased. Tansky barbels have only six or seven of them. By exposing them to high doses of thyroid hormone, we managed to achieve an even more noticeable reduction in their number. When the caddisflies’ larvae were kept in conditions of hormone deficiency, the number of supraneuralia increased, and it was established that each of them is a complex bone formed as a result of the fusion of several rudiments. Similar consequences of changes in hormone levels were found in other skeletal structures. This means that a decrease in thyroid hormone levels during development partially returns the living being to its ancestral state, while high hormone levels lead to the appearance of more evolutionarily advanced features. These facts suggest that changes in hormonal regulation may underlie the formation not only of species but also of higher-order groups, as Goldschmidt suggested.

How did it happen that Lake Tana was so quickly colonised by such different species descended from the same ancestor? Obviously, when the ancestral species inhabited the lake, there was a very poor ichthyofauna and many places where it was possible to settle, and with quite diverse conditions. There are deep places, shallow waters, areas with different oxygen concentrations and different amounts of food, with weak water mixing, there are areas where rivers flow into the lake with a large outflow. And oxygen demand and active behaviour are also directly related to metabolic rate and therefore thyroid hormone levels. Variability in metabolic rate allowed the ancestral species to occupy different habitats and do well in each. In 2010, Japanese biologist Jun Kitano and his colleagues from Japan and the US studied a fish called the three-headed stickleback. It has two forms: marine (historically primary) and riverine, which evolved as a result of sticklebacks colonising freshwater bodies. Sea and river sticklebacks differ not only in habitat, but also in morphology and physiology. Kitano managed to establish the difference between them in the level of thyroid hormone and proved that this difference is inherited, i.e. fixed genetically. Low levels of the hormone are adaptive for living in places with a lack of oxygen and reduced food resources. Active forms require higher levels. Thus, different levels of the hormone contributed to the separation of forms of the same species by habitat and actually created the prerequisites for the emergence of new species. It is likely that something similar happened in Lake Tana, but the reason for the rapid evolution of the whiskers remains to be seen. Whether we find this reason in genetic mutations or in the field of epigenetics, i.e. in changes in the expression of the same genes, will show further research. But already now we can say with a high degree of certainty that thyroid hormone has played a serious role in evolutionary transformations.