- Open Access
How the vertebrates were made: selective pruning of a double-duplicated genome
© Manning and Scheeff; licensee BioMed Central Ltd. 2010
- Received: 6 December 2010
- Accepted: 7 December 2010
- Published: 13 December 2010
Vertebrates are the result of an ancient double duplication of the genome. A new study published in BMC Biology explores the selective retention of genes after this event, finding an extensive enrichment of signaling proteins and transcription factors. Analysis of their expression patterns, interactions and subsequent history reflect the forces that drove their evolution, and with it the evolution of vertebrate complexity.
See research article: http://www.biomedcentral.com/1741-7007/8/146/abstract
- Epidermal Growth Factor Receptor
- Whole Genome Duplication
- Whole Genome Duplication Event
- Dosage Sensitivity
- Small Scale Duplication
Another receptor tyrosine kinase (RTK) family, the Ephs, has expanded by WGD and SSD from one gene in invertebrates to 14 in human, giving rise to a similar explosion in complexity through heterodimerization and ligand cross-talk. This richness is used extensively in developmental patterning, and demonstrates continued evolvability. For instance, in chicken, graded expression of EphA3 across the retina provides the basis for spatial mapping of retinal ganglion cells projecting to the tectum . However, in mouse, EphA3 is not expressed in these cells, and instead EphA5 and EphA6 fulfill this role, suggesting that new and swapped functions can emerge from duplicates long after they have acquired essential roles, and that WGD can represent a quantum leap in the potential for new complexity and evolvability within the vertebrates. We estimate that, excluding the Ephs, 2R caused an expansion of RTKs from 20 to 46, but only two new human RTKs have emerged since then (ES and GM, unpublished): the two rounds of WGD thus seem to have been crucially important in shaping human RTK signaling.
One notable aspect of the patterns reported by Huminiecki and Heldin is how similar they are to those seen in other WGD events [8–10]. Enrichment in signaling proteins and transcription factors has also been seen in WGD from yeast, plants, and fish. Conversely, other genes (mostly those involved in basic cellular processes) preferentially return to singleton status, and similarities in these loss patterns can also be detected across kingdoms. While SSDs show more lineage-specific variability, there are also similarities, such as the increased SSD rate in plant secondary metabolic genes involved in pathogen defense  mimicking the increased vertebrate SSD in immune genes.
It is tempting to speculate from these observations that WGD produces a consistent drive towards higher complexity , and the two rounds of vertebrate WGD doubly so. However, it is a vexed question exactly what is meant by complexity. It is not clear, for example, that fish and frogs, which have undergone an extra round of genome duplication, are more complex than humans, which have not.
The kind of molecular archaeology pursued by Huminiecki and Heldin is not just of academic interest: detailed comparison of ohnologs from many species can provide the unique sequence signatures underlying their specific functions, and patterns of gain or loss can help us to understand functional interactions between genes. As more vertebrate genomes become available, we will gain greater precision in determining orthology, synteny and post-2R changes. Knowing the trends in ohnolog retention and the history of human genes will help us to better understand their dosage sensitivity, and the shared and unique functions of all ohnologs.
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