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The first fly embryos were stained for three target genes Bcd, Otd (light blue), Hb (dark blue) and Kr (red). Credit: Rhea Datta.
Scientists from the University of New York and the University of Chicago have created fruit flies carrying reconstructed old genes, revealing how ancient mutations have led to major evolutionary changes in embryonic development, including we are seeing the impact today.
The work, published in the journal eLife, discovered that two mutations occurred 140 million years ago have altered the function of a critical gene of development, which now regulates the development of the head and other structures in virtually all current fly species.
"By introducing into the old genes individual mutations that occurred in the deep past, we were able to show precisely how each of them had affected development millions of years ago," says Stephen Small, a biologist with NYU and one of the main authors of the newspaper.
"We discovered that two fortuitous mutations were the main causes of a profound change in the processes of animal development – a change that has become indispensable in all of its current descendants," says Joseph Thornton, another author main newspaper and professor of ecology. and evolution and human genetics at the University of Chicago.
Scientists have long sought to understand how genetic mutations modify embryonic development to produce the various animal forms we observe today. But identifying important mutations is very difficult because they have occurred in the deep past, in animals long extinct, and they have usually been mixed with dozens of subsequent mutations.
The NYU and Thornton Small laboratories of the University of Chicago have tackled this problem in an innovative way: computationally deduce ancient gene sequences based on their modern descendants, chemically recreate the genes, and then place them in embryos of flies, thus creating transgenic embryos, namely: those inserted with a foreign gene – to track their effects on development in the laboratory.
The study is the first to use ancestral reconstruction in the field of evolution of development, or evo-devo.
The researchers focused on the evolution of a gene called bicoide. The bicoid triggers the formation of structures at the (anterior) head of fruit fly embryos, an important model organism because many aspects of its genetics and development are shared with humans and others animals. Bicoid serves as the "main regulator" of previous development by activating the expression of a set of genes that ensure the development of the head and suppress the development of the tail, and only at the end earlier.
Bicoid has long presented an evolutionary puzzle. Flies embryos lacking active Bcd protein die very early because instead of forming a head, they form a structure of the tail at both ends. But the bicoid gene does not even exist in other insects or in more distant relatives, who use other genes to control the previous development. Bicoid shows that even the most basic aspects of development can change dramatically in the course of evolution, but the way this process occurs is unknown.
The Small and Thornton laboratories sought to understand how the new development function of the bicoide evolved: to recreate the precursor gene from which it was derived, to characterize its biochemical functions, to introduce it into modern fruit flies whose bicoid gene had been removed , study its effects on the formation of head structures and the expression of specific genes that govern the development of the head, and the introduction of historical mutations in the ancestral gene to determine their effects.
Their first results showed that flies carrying the precursor gene do not develop head, with tails at both ends and none of the key genes involved in the development of the head is correctly expressed. The group then introduced into the precursor gene all the mutations that occurred during the old interval in which the bicoid evolved.
Most of the changes had little or no effect on the functions of the bicoide, but two of them together allowed the latter to activate a completely new set of target genes. When introduced into fly embryos, this bicoid evolutionary version of the bicoid gene activated most of the genes involved in head development, and the embryos formed recognizable, although incomplete, head structures at the same time. place tail structures at the anterior end.
The group concluded that these two mutations, when combined, were the predominant causes of the functional evolution of the bicoid, with additional mutations during the same ancient period, allowing to refine the new function of the gene.
"By combining the most advanced techniques of developmental biology and evolutionary genetics, we have been able to dissect the way in which the molecular modifications of an ancient gene have fundamentally altered one of the most important processes – and the most conserved – of animal development, "says Small.
Explore further:
Genetic changes in basic development processes evolve more frequently than expected
More information:
Qinwen Liu et al, Ancient Mechanisms for the Evolution of the Function of the Bicoid Homeodomain in the Development of Flies, eLife (2018). DOI: 10.7554 / eLife.34594
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