Homeotic genes are genes which regulate the development of anatomical structures in various organisms such as echinoderms,[1] insects, mammals, and plants. Homeotic genes often encodetranscription factor proteins, and these proteins affect development by regulating downstream gene networks involved in body patterning.[2]
Mutations in homeotic genes cause displaced body parts (homeosis), such as antennae growing at the posterior of the fly instead of at the head.[3] Mutations that lead to development of ectopic structures are usually lethal.[4]
There are several subsets of homeotic genes. They include many of theHox andParaHox genes that are important forsegmentation.[5] Hox genes are found in bilateral animals, includingDrosophila (in which they were first discovered) and humans. Hox genes are a subset of thehomeobox genes. The Hox genes are oftenconserved across species, so some of the Hox genes ofDrosophila are homologous to those in humans. In general, Hox genes play a role of regulating expression of genes as well as aiding in development and assignment of specific structures during embryonic growth. This can range from segmentation inDrosophila tocentral nervous system (CNS) development in vertebrates.[6] Both Hox and ParaHox are grouped as HOX-Like (HOXL) genes, a subset of the ANTP class (named after theDrosophila gene,Antennapedia).[7]
They also include theMADS-box-containing genes involved in theABC model of flower development.[8] Besides flower-producing plants, the MADS-box motif is also present in other organisms such as insects, yeasts, and mammals. They have various functions depending on the organism including flower development, proto-oncogene transcription, and gene regulation in specific cells (such as muscle cells).[9]
Despite the terms being commonly interchanged, not all homeotic genes are Hox genes; the MADS-box genes are homeotic but not Hox genes. Thus, the Hox genes are a subset of homeotic genes.
One of the most commonly studiedmodel organisms in regards to homeotic genes is the fruit flyDrosophila melanogaster. Its homeotic Hox genes occur in either the Antennapedia complex (ANT-C) or the Bithorax complex (BX-C) discovered byEdward B. Lewis.[10] Each of the complexes focuses on a different area of development. Theantennapedia complex consists of five genes, includingproboscipedia, and is involved in the development of the front of the embryo, forming the segments of the head and thorax.[11] The bithorax complex consists of three main genes and is involved in the development of the back of the embryo, namely the abdomen and the posterior segments of the thorax.[12]
During development (starting at theblastoderm stage of the embryo), these genes are constantly expressed to assign structures and roles to the different segments of the fly's body.[13]
Much research has been done on homeotic genes in different organisms, ranging from basic understanding of how the molecules work to mutations to how homeotic genes affect the human body. Changing the expression levels of homeotic genes can negatively impact the organism. For example, in one study, a pathogenic phytoplasma caused homeotic genes in a flowering plant to either be significantly upregulated or downregulated. This led to severe phenotypic changes including dwarfing, defects in the pistils, hypopigmentation, and the development of leaf-like structures on most floral organs.[14] In another study, it was found that the homeotic geneCdx2 acts as atumor suppressor. In normal expression levels, the gene prevents tumorgenesis and colorectal cancer when exposed tocarcinogens; however, whenCdx2 was not well expressed, carcinogens caused tumor development.[15] These studies, along with many others, show the importance of homeotic genes even after development.