Aug. 18, 2004 With increasing numbers of whole genomes being sequenced, researchers are keen to analyse the functions of the genes they contain and the proteins these genes encode. Yet, according to researchers writing in BMC Biology, to fully understand any genome, researchers must use palaeontology, geology and chemistry to help them discover the reasons why specific genes evolved.
Steven Benner and Eric Gaucher at the Foundation for Applied Molecular Evolution, Frank and Rosalie Simmen at the University of Arkansas, and their colleagues from the United States and Norway carried out the study. They used a diverse array of disciplines to investigate why the pig, Sus scrofa, has three different genes that encode the enzyme aromatase – an enzyme that catalyses the transformation of androgens, such as testosterone, into estrogens - whereas other hooved animals have only one.
The evidence that they collected suggests that the additional aromatase genes arose as a result of natural selection for pigs with larger litters than their ancestors. These larger litters may well have helped the animals to survive the dramatic cooling of the earth that started during the Oligocene period, around 35 million years ago.
Their investigations drew on the geological and palaeontological records, and used techniques from evolutionary biology, structural biology, chemistry and genetics. "As the geological, palaeontological and genomic records improve," write the authors, "our combined approach should become widely useful to make systems biology statements about high-level function for biomolecular systems. […] Over the long term, we expect that the histories of the geosphere, the biosphere and the genosphere will converge to give a coherent picture showing the relationship between life and the planet that supports it."
The researchers used genetic information to estimate that the ancestral aromatase gene duplicated twice, to give three genes, between 27 and 38 million years ago. By analysing the genetic sequence from two living relatives of Sus scrofa, peccary and babirusa, the researchers were able to narrow this time period further. As both these relatives have two genes encoding aromatases, one more than most hooved animals, the first gene duplication is likely to have occurred in the common ancestor of the three animals, around 35 million years ago. This coincides with the climate changes that started in the Oligocene.
By consulting the palaeontological record, which contains fossils of pregnant animals, the researchers found that the increase in the number of aromatase genes coincided with the emergence of larger litter sizes. Ancestral hooved animals produced between one and two offspring at a time, whereas peccaries produce at least two offspring, and the true pigs, such as Sus scrofa, routinely have between three and four young. This evidence suggested that the new aromatase genes could have played a role in altering the reproductive behaviour of the animals.
By studying the structure of the different enzymes encoded by the three genes, Dr Benner and his colleagues found small differences in the amino acid sequences within the protein's substrate-binding and active sites. This suggests that the three enzymes bind to different molecules, so each aids the formation of different products. It is the evolution of these different catalytic activities that might have caused changes in the pig's reproductive biology.
Obviously, the evolution of the aromatase genes is likely to be only a small part of the changes in reproductive endocrinology that enabled these animals to make the transition from small to large litter sizes. However, the multi-disciplinary analysis does go some way towards explaining why natural selection would have favoured pigs with multiple aromatase genes.
Dr Benner writes: "Natural history offers biological chemists the opportunity to place broad biological meaning on the detailed analysis of the changing structure of isolated biological molecules, studied in a reductionist setting. To do so, however, natural history must be connected to the physical and molecular sciences, both in subject matter and in culture."
### This press release is based on the following article:
The planetary biology of cytochrome P450 aromatases
Eric A Gaucher, Logan G Graddy, Tang Li, Rosalia CM Simmen, Frank A Simmen, David R Schreiber, David A Liberles, Christine M Janis and Steven A Benner BMC Biology 2004, 2:18 To be published Tuesday 17 August, 2004
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