HOX GENES: DISCOVERY, CHARACTERISTICS AND EVOLUTION - BIOLOGY - 2025

The Hox genes are a large gene family that are responsible for regulating the development of body structures. They have been found in all metazoans and in other lineages, such as plants and animals. Therefore, they are characterized by being evolutionarily very conserved.

These genes work as follows: they code for a transcription factor - a protein capable of interacting with DNA - which is expressed in a specific area of ​​the individual from the earliest stages of development. This DNA binding sequence is called a homeobox.

Source: Antonio Quesada Díaz, via Wikimedia Commons

With almost 30 years of research in this field, scientists have studied different lineages and have concluded that the expression patterns of these genes are strongly associated with the regionalization of the body axes.

This evidence suggests that the Hox genes have played an indispensable role in the evolution of the bodily plans of living beings, particularly in Bilateria. Thus, the Hox genes have made it possible to explain the magnificent diversity of animal forms, from a molecular perspective.

In us humans, there are 39 Hox genes. These are grouped into four clusters or groups, located on different chromosomes: 7p15, 17q21.2, 12q13 and 2q31.

Discovery

The discovery of the Hox genes was a milestone in evolutionary and developmental biology. These genes were discovered between the 70s and 80s thanks to the observation of two key mutations in the fruit fly, Drosophila melanogaster.

One of the mutations, antennapedia, transforms the antennae into legs, while the bithorax mutation causes the transformation of halteres (modified structures, typical of winged insects) into another pair of wings.

As can be seen, when the Hox genes have mutations, the result of this is quite dramatic. And, as in Drosophila, the change leads to the formation of structures in the wrong places.

Before the discovery of the Hox genes, most biologists believed that morphological diversity was supported by variety at the DNA level. It was logical to assume that the obvious differences between a whale and a hummingbird, for example, had to be reflected in genetic terms.

With the advent of the Hox genes, this thinking took a complete turn, giving way to a new paradigm in biology: a common pathway of genetic development that unifies the ontogeny of Metazoans.

What are Hox genes?

Before defining the concept of Hox genes, it is essential to know what a gene is and how it works. Genes are DNA sequences whose message is expressed in a phenotype.

The message of DNA is written in nucleotides, in some cases these pass into a messenger RNA and this is translated by ribosomes into a sequence of amino acids - the structural "building blocks" of proteins.

Hox genes are the best-known class of homeotic genes, whose function is to control specific patterns of body structures. These are in charge of controlling the identity of the segments along the anteroposterior axis of the animals.

They belong to a single family of genes that codes for a protein that has a specific amino acid sequence capable of interacting with the DNA molecule.

This is where the term homeobox comes from to describe this section in the gene, while in the protein it is called homeodomain. The homeobox sequence has a sequence of 180 base pairs and these domains are evolutionarily highly conserved among different Phyla.

Thanks to this interaction with DNA, the Hox genes are able to regulate the transcription of other genes.

Terminology

The genes involved in these morphological functions are called homeotic loci. In the animal kingdom, the most important ones are known as HOM loci (in invertebrates) and Hox loci (in vertebrates). However, they are generally known as Hox loci.

characteristics

The Hox genes have a series of very peculiar and interesting characteristics. These key aspects help to understand its functioning and its potential role in evolutionary biology.

These genes are organized into "gene complexes", which means that they are close together on the chromosomes - in terms of their spatial location.

The second characteristic is the surprising correlation that exists between the order of the genes in the DNA sequence and the anteroposterior location of the products of these genes in the embryo. Literally the genes that go "forward" are in that position.

Similarly, in addition to spatial collinearity, there is a temporal correlation. Genes located at the 3 'end occur earlier in the development of the individual, compared to those found further back.

The Hox genes belong to a class called ANTP, which also includes the ParaHox genes (related to these), NK genes, and others.

Evolution of genes

No genes of the ANTP class were from the Metazoans. In the evolutionary development of this animal group, the porifers were the first group to separate, followed by the cnidarians. These two lineages represent the two basal groups of bilaterals.

Genetic analysis performed on the famous sponge Amphimedon queenslandica - its fame is due to genes for the nervous system - revealed that this poriferous has several genes of the NK type, but no Hox or ParaHox genes.

Hox genes as such have not been reported in cnidarians that meet the aforementioned characteristics. However, there are Hox-like genes.

On the other hand, invertebrates have a single cluster of Hox genes, while vertebrates have multiple copies. This fact has been crucial and has inspired the development of theories about the evolution of the group.

Origin of vertebrates

The classical view of this aspect argues that the four gene clusters in the human genome originated thanks to two rounds of replication of the entire genome. However, the development of new sequencing technologies has cast doubt on the theory.

The new evidence favors the hypothesis related to small-scale events (segment duplication, individual duplication of genes and translocations) that achieved the high number of Hox genes that we observe today in this group.

References

1. Acampora, D., D'esposito, M., Faiella, A., Pannese, M., Migliaccio, E., Morelli, F.,… & Boncinelli, E. (1989). The human HOX gene family. Nucleic acids research, 17 (24), 10385-10402.
2. Ferner, DE (2011). Hox and ParaHox genes in evolution, development and genomics. Genomics, proteomics & bioinformatics, 9 (3), 63-4.
3. Hrycaj, SM, & Wellik, DM (2016). Hox genes and evolution. F1000Research, 5, F1000 Faculty Rev-859.
4. Lappin, TR, Grier, DG, Thompson, A., & Halliday, HL (2006). HOX genes: seductive science, mysterious mechanisms. The Ulster medical journal, 75 (1), 23-31.
5. Pearson, JC, Lemons, D., & McGinnis, W. (2005). Modulating Hox gene functions during animal body patterning. Nature Reviews Genetics, 6 (12), 893.