page_title: Hox genes in amphibians and reptiles
section_title: Hox clusters
hierarchical_section_title: Hox genes in amphibians and reptiles / Hox clusters
caption_attribution_description: Notophthalmus viridescens العربية: سمندر مائي شرقي أحمر. المكان: مُقاطعة دورهام، كارولينا الشماليَّة، الولايات المُتحدة. (نسخة جديدة، 1600 عنصورة (پكسل) عرضًا، عُدِّل توازن الألوان، رُفعت يوم 29 تشرين الثاني (نوڤمبر) 2007.) English: Eastern Newt (Red Eft). Location: Durham County, North Carolina, United States. (New version, 1600 pixels width, color balance adjusted, uploaded 29 November 2007.)
context_page_description: Hox genes play a massive role in some amphibians and reptiles in their ability to regenerate lost limbs, especially HoxA and HoxD genes.
  If the processes involved in forming new tissue can be reverse-engineered into humans, it may be possible to heal injuries of the spinal cord or brain, repair damaged organs and reduce scarring and fibrosis after surgery. Despite the large conservation of the Hox genes through evolution, mammals and humans specifically cannot regenerate any of their limbs. This raises a question as to why humans which also possess an analog to these genes cannot regrow and regenerate limbs. Beside the lack of specific growth factor, studies have shown that something as small as base pair differences between amphibian and human Hox analogs play a crucial role in human inability to reproduce limbs. Undifferentiated stem cells and the ability to have polarity in tissues is vital to this process.
context_section_description: As previously mentioned, Hox genes encode transcription factors that regulate embryonic and post-embryonic developmental processes.  The expression of Hox genes is regulated in part by the tight, spatial arrangement of conserved coding and non-coding DNA regions. The potential for evolutionary alterations in Hox cluster composition is viewed to be small among vertebrates. On the other hand, recent studies of a small number of non-mammalian taxa propose greater dissimilarity than initially considered. Next, generation sequencing of considerable genomic fragments greater than 100 kilobases from the eastern newt (Notophthalmus viridescens) was analyzed. Subsequently, it was found that the composition of Hox cluster genes were conserved relative to orthologous regions from other vertebrates. Furthermore, it was found that the length of introns and intergenic regions varied. In particular, the distance between HoxD13 and HoxD11 is longer in newt than orthologous regions from vertebrate species with expanded Hox clusters and is predicted to exceed the length of the entire HoxD clusters (HoxD13–HoxD4) of humans, mice, and frogs. Many recurring DNA sequences were recognized for newt Hox clusters, counting an enrichment of DNA transposon-like sequences similar to non-coding genomic fragments. Researchers found the results to suggest that Hox cluster expansion and transposon accumulation are common features of non-mammalian tetrapod vertebrates.
  After the loss of a limb, cells draw together to form a clump known as a blastema. This superficially appears undifferentiated, but cells that originated in the skin later develop into new skin, muscle cells into new muscle and cartilage cells into new cartilage. It is only the  cells from just beneath the surface of the skin that are pluripotent and able to develop into any type of cell. Salamander Hox genomic regions show elements of conservation and variety in comparison to other vertebrate species. Whereas the structure and organization of Hox coding genes is conserved, newt Hox clusters show variation in the lengths of introns and intergenic regions, and the HoxD13–11 region exceeds the lengths of orthologous segments even among vertebrate species with expanded Hox clusters. Researchers have suggested that the HoxD13–11 expansion predated a basal salamander genome size amplification that occurred approximately 191 million years ago, because it preserved in all three extant amphibian groups. Supplementary verification supports the proposal that Hox clusters are acquiescent to structural evolution and variation is present in the lengths of introns and intergenic regions, relatively high numbers of repetitive sequences, and non-random accumulations of DNA transposons in newts and lizards. Researchers found that the non-random accretion of DNA-like transposons could possibly change developmental encoding by generating sequence motifs for transcriptional control.
  In conclusion, the available data from several non-mammalian tetrapods suggest that Hox structural flexibility is the rule, not the exception. It is thought that this elasticity may allow for developmental variation across non-mammalian taxa. This is of course true for both embryogenesis and during the redeployment of Hox genes during post-embryonic developmental processes, such as metamorphosis and regeneration.
caption: The eastern newt (Notophthalmus viridescens)
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