In his essay Evolution and Tinkering, published in Science in 1977, Francois Jacob argued that a common analogy between the process of evolution by natural selection and the methods of engineering is problematic. Instead, he proposed to describe the process of evolution with the concept of bricolage (tinkering). In this essay, Jacob did not deny the importance of the mechanism of natural selection in shaping complex adaptations. Instead, he maintained that the cumulative effects of history on the evolution of life, made evident by molecular data, provides an alternative account of the patterns depicting the history of life on earth. Jacob's essay contributed to genetic research in the late twentieth century that emphasized certain types of topics in evolutionary and developmental biology, such as genetic regulation, gene duplication events, and the genetic program of embryonic development. It also proposed why, in future research, biologists should expect to discover an underlying similarity in the molecular structure of genomes, and that they should expect to find many imperfections in evolutionary history despite the influence of natural selection.

The hedgehog signaling pathway is a mechanism that directs the development of embryonic cells in animals, from invertebrates to vertebrates. The hedgehog signaling pathway is a system of genes and gene products, mostly proteins, that convert one kind of signal into another, called transduction. In 1980, Christiane Nusslein-Volhard and Eric F. Wieschaus, at the European Molecular Biology Laboratory in Heidelberg, Germany, identified several fruit fly (Drosophila melanogaster) genes. They found that when those genes were changed or mutated, the mutated genes disrupted the normal development of fruit fly larvae. The researchers called one of the genes hedgehog (abbreviated hh). Nusslein-Volhard, Wieschaus, and Edward B. Lewis, at the California Institute of Technology in Pasadena, California, shared the 1995 Nobel Prize for Physiology or Medicine for their research on how genes control early embryonic development in fruit flies. The hedgehog signaling pathway is conserved across many animal taxa or phyla, from Drosophila to humans. The hedgehog signaling pathway controls several key components of embryonic development, stem-cell maintenance, and it influences the development of some cancers.

Walter Jakob Gehring discovered the homeobox, a DNA segment found in a specific cluster of genes that determine the body plan of animals, plants, and fungi. Gehring identified the homeobox in 1983, with the help of colleagues while isolating the Antennapedia (Antp) gene in fruit flies (Drosophila) at the University of Basel in Basel, Switzerland. Hox genes, a family of genes that have the homeobox, determine the head-to-tail (anterior-posterior) body axis of both vertebrates and invertebrates. Gehring also identified the homeobox-containing Pax-6 gene as the master control gene in eye development of Drosophila, the same gene that, when mutated or absent in humans, leads to aniridia, or lack of the iris, in humans. Gehring's work with the homeobox suggested to biologists that widely different species share a similar and evolutionarily conserved genetic pathway that controls the development of overall body plans, from fruit flies to humans.

In the early 2000s, Manjong Han, Xiaodang Yang, Jennifer Farrington, and Ken Muneoka investigated how genes and proteins in fetal mice (Mus musculus) influenced those fetal mice to regenerate severed toes at Tulane University in New Orleans, Louisiana. The group used hind limbs from mice to show how the gene Msx1 (Homeobox 7) functions in regenerating amputated digits. The researchers showed that in the process of regenerating digit tips, Msx1 genes make products that regulate or influence other genes, such as the Bone Morphogenetic Protein 4 gene (BMP4 gene), to produce proteins, such as the BMP4 proteins. The researchers also showed that BMP4 proteins, which are produced from the BMP4 gene, function in tissues during the process of limb development. Furthermore, while Msx1 genes regulate other genes during the process of regeneration, they don't produce proteins otherwise needed to organize cells in the regeneration of digit tissues. The group published their results in 2003 as Digit Regeneration Is Regulated by Msx1 and BMP4 in Fetal Mice.

In 1995, researchers Ann Burke, Craig Nelson, Bruce Morgan, and Cliff Tabin in the US studied the genes that regulate the construction of vertebra in developing chick and mouse embryos, they showed similar patterns of gene regulation across both species, and they concluded that those patterns were inherited from an ancestor common to all vertebrate animals. The group analyzed the head-to-tail (anterior-posterior) axial development of vertebrates, as the anterior-posterior axis showed variation between species over the course of evolutionary time. Along those axes, they showed where Hox genes produced RNAs. Hox genes have the homeobox, a portion of DNA contributes to the generation of the body plans of animals, plants, and fungi. In the 1995 study, the researchers compared the expression patterns of Hox genes across the chick and mouse embryos, showing where the patterns were similar and where they differed. Based on those comparisons, they argued that Hox genes were present in the ancestors of tetrapods and fishes, and that Hox genes function in the segmentation of the anterior-posterior vertebrate axis in both chick and mouse embryos.

Homeobox genes are a cluster of regulatory genes that are spatially and temporally expressed during early embryological development. They are interesting from both a developmental and evolutionary perspective since their sequences are highly conserved and shared across an enormously wide array of living taxa.

Bicoid is the protein product of a maternal-effect gene unique to flies of the genus Drosophila . In 1988 Christiane Nüsslein-Volhard identified bicoid as the first known morphogen . A morphogen is a molecule that determines the fate and phenotype of a group of cells through a concentration gradient across that developing region. The bicoid gradient, which extends across the anterior-posterior axis of Drosophila embryos, organizes the head and thorax.