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Origin of limbs in the evolutionary lineage of vertebrates

Date:
June 21, 2012
Source:
Universidad de Barcelona
Summary:
A chromosomal rearrangement in the genome could be the genetic base of the origin of limbs in vertebrates, according to a new research.

Genomic location of tissue-specific Shh enhancers in mouse and zebrafish.
Credit: Image courtesy of Universidad de Barcelona

A chromosomal rearrangement in the genome could be the genetic base of the origin of limbs in vertebrates, according to a new research published online in the Nature Scientific Reports and which has been led by experts Jordi Garcia-Fernández and Manuel Irimia, from the Department of Genetics and from the Institute of Biomedicine of the University of Barcelona (IBUB), affiliated centre to the campus of international excellence Barcelona Knowledge Campus (BKC).

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This new research focuses on the study of the Sonic Hedgehog (Shh) gene, a morphogen located on the short arm of the chromosome 7. As professor Jordi Garcia- Fernández, head of the Reg-Volution Lab of the UB, explains, "the Shh gene is a key factor in the embryogenesis and in the development of various structures (nervous system, limbs, gastrointestinal tract). In vertebrates, this gene is mainly expressed in the brain and the limbs. If you delete it, limbs are not developed. Alterations of this gene are associated with several diseases of the nervous system."

Reconstructing the evolutionary lineage between invertebrates and vertebrates

The scientific research studies Hedgehog loci in three species of amphioxus: Branchiostoma floridae (United States), Branchiostoma lanceolatum (Europe) and Branchiostoma belcheri (Asia), which are animal models of reference in genomics and the oldest representatives of the phylum of chordates. Using bioinformatic analysis of genomic sequences and zebrafish transgenesis, the study compares the ancestral genetic architecture of Hedgehog gene with that of the three representatives of the Hedgehog family in vertebrates: Sonic Hedgehog (Shh), Desert Hedgehog (Dhh), and Indian Hedgehog (Ihh) gene.

One of the most surprising results is that the regulatory region (the enhancer) that directs the expression of Shh gene in vertebrate limbs is located within another gene -Lmbr1-, at a distance of one thousand kilobases. In the case of the development of the nervous system, the distance between the gene and the regulatory region is considerably shorter (tens of kilobases).

From the expression in the brain to the origin of the limbs

Why is Shh gene also important in developing limbs? Why is it located so far away from the regulatory region? To answer these questions, the experts have studied the regulation of genes (synteny) in the species that have been compared. "The regulatory regions that determine the expression of Shh in the brain are well characterised and are very close to this gene," explains Garcia-Fernández. "According to our study, about 400 million years ago, as a result of a chromosomal translocation, which is an exchange of fragments between chromosomes, Lmrb gene was placed near Shh gene, acquiring a new function in vertebrate phylogeny: the development of limbs." Hence, the study shows that what could be considered a genetic mistake -in this case, a translocation- resulted in the expression of the Shh gene in a new area and in the origin of vertebrate limbs.

When the whole genome was duplicated

The study provides new data to the scientific debate on the 2R hypothesis, which explains the origin of the vertebrate genome from two ancestral genomic duplications. According to this hypothesis, the two consecutive duplications of an ancestral genome are the origin of major gene families in vertebrates, a process by which genes could also acquire new functions. The authors of the paper claim that Shh and Dhh genes originated in the second round of the whole genome duplication, whereas Ihh gene, which is not influenced by the regulatory region of Lmbr1 gene, would even be a more ancestral copy in the phylogenetic scale.

Chromosomal rearrangements are changes in the genome architecture that change the location and function of genes. Hence, they are key processes in the dynamical evolution of genomes and in the species adaptation process to their environment. "Chromosomal rearrangements -points out Garcia-Fernández- are common phenomena in the biological evolution. We know, for example, that genomes of mouse and man are quite similar and that they differ by many chromosomal rearrangements. These genetic mistakes are the engine to many changes in the genome, as it has been seen with the two rounds of the whole genome duplication in the origin of vertebrates, and now also in the case of the expression of Shh gene in the origin of vertebrate limbs."

This new study, which deepens the understanding of the patterns of physical development in vertebrates, is also signed by experts Ignacio Maeso and Demian Burguera, from the Department of Genetics of the UB, and by José Luis Gómez-Skarmeta and José L. Royo, from the Andalusian Centre for Developmental Biology (CSIC).


Story Source:

The above story is based on materials provided by Universidad de Barcelona. Note: Materials may be edited for content and length.


Journal Reference:

  1. Manuel Irimia, Jose L. Royo, Demian Burguera, Ignacio Maeso, José L. Gómez-Skarmeta, Jordi Garcia-Fernandez. Comparative genomics of the Hedgehog loci in chordates and the origins of Shh regulatory novelties. Scientific Reports, 2012; 2 DOI: 10.1038/srep00433

Cite This Page:

Universidad de Barcelona. "Origin of limbs in the evolutionary lineage of vertebrates." ScienceDaily. ScienceDaily, 21 June 2012. <www.sciencedaily.com/releases/2012/06/120621125441.htm>.
Universidad de Barcelona. (2012, June 21). Origin of limbs in the evolutionary lineage of vertebrates. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2012/06/120621125441.htm
Universidad de Barcelona. "Origin of limbs in the evolutionary lineage of vertebrates." ScienceDaily. www.sciencedaily.com/releases/2012/06/120621125441.htm (accessed December 21, 2014).

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