The review by Hunter Fraser discusses the role of gene expression in adaptation, the challenges facing the field, recent genome-wide studies that allow the rejection of the null model of neutrality and how the latter thus help to determine, with some confidence, if positive selection is occurring. He then goes on to discuss questions that can be addressed and the empirical evidence available for answering these.
Challenges in studying gene expression adaptation:
The author discusses the two important stages at which adaptation can occur – the inherent sequences of proteins and the pattern and level of expression of these proteins. Protein sequence evolution and its role in adaptation have received a lot of attention from the scientific community and have been widely studied. The study of gene expression adaptation (GEA) on the other hand, has been very limited. There are three reasons for this aberration – the little significance attributed to GEA in adaptation as compared to protein sequences until recently (as recent as 2003!), difficulty to characterize gene regulation as compared to deducing DNA sequences, mainly because of its dynamic nature, and thus the unavailability of suitable methods for simple and effective study of GEA.
Genome wide studies – Vm and sign tests:
The most important problem in tests of selection are determining a neutral reference for comparison of all results, and availability of adequate data to satisfactorily dismiss the null model of neutrality. Genome scale studies can help in providing an unbiased repertoire of data for this purpose. There are two strategies currently used in genome-wide studies on GEA.
Future questions:
The author discusses a number of future questions that need to be addressed in the field. Some supporting evidence is already available for answering some of these questions. However, everyone in the group thought that these were majorly open-ended questions and possibilities, and the little evidence that was available was inadequate to establish any answers. However, the preliminary data available was interesting and some of the questions were discussed in detail.
“How often is GEA tissue or condition-specific?”
GEA offers an amazing advantage in that selection is based on the level of functioning of the genotype and requires no change in the protein sequence. This leads to the question if GEA occurs across all tissues or in certain tissues, as well if certain conditions cause GEA. The genome-wide study for tissue specificity was thought to be inadequate in terms of number of tissues studied.
“Does GEA affect single mutations of large effect or many mutations of smaller effect”
Genome-wide studies show that mutations of smaller effect are generally involved in GEA. It was discussed that single mutations of large effect might be economical for causing adaptation. However, the probability of single mutations reverting would be harmful for the individual and hence many mutations of small effect would provide a more robust path for GEA.
“Does GEA affect particular types of traits or genes”
Genome-wide studies can only help in answering this question without any bias. This question is important because if GEA affects a gene involved in many pathways, it can have a widespread effect.
“Are most evolutionary adaptations due to GEA or protein-coding changes or both?”
It is interesting that a genome-wide study indicates GEA to be the major contributor to evolution. This is interesting in light of the earlier question “What fraction of gene expression change is adaptive?” because a very small fraction of gene expression change is adaptive, but this little change is responsible for most adaptations.
Almost all of the questions require broad and intensive genome-scale studies to satisfactorily establish any results. The ability to detect a change and the choice of genes severely affects the results of the experiment. Also, robust methods need to be developed that can satisfactorily answer the impendig questions. Overall, the paper does a good job of presenting the new genome-scale strategies used to study GEA and the questions that need to be addressed in the field, constantly stressing on the importance of genome-wide studies in each case.
My views on the paper:
Fraser, H. (2011). Genome-wide approaches to the study of adaptive gene expression evolution BioEssays, 33 (6), 469-477 DOI: 10.1002/bies.201000094