@article {19364735,
	title = {Sexual selection drives weak positive selection in protamine genes and high promoter divergence, enhancing sperm competitiveness},
	journal = {Proc Biol Sci},
	year = {2009},
	note = {<p>Journal article Proceedings. Biological sciences / The Royal Society Proc Biol Sci. 2009 Apr 8.</p>},
	abstract = {<p>Phenotypic adaptations may be the result of changes in gene structure or gene regulation, but little is known about the evolution of gene expression. In addition, it is unclear whether the same selective forces may operate at both levels simultaneously. Reproductive proteins evolve rapidly, but the underlying selective forces promoting such rapid changes are still a matter of debate. In particular, the role of sexual selection in driving positive selection among reproductive proteins remains controversial, whereas its potential influence on changes in promoter regions has not been explored. Protamines are responsible for maintaining DNA in a compacted form in chromosomes in sperm and the available evidence suggests that they evolve rapidly. Because protamines condense DNA within the sperm nucleus, they influence sperm head shape. Here, we examine the influence of sperm competition upon protamine 1 and protamine 2 genes and their promoters, by comparing closely related species of Mus that differ in relative testes size, a reliable indicator of levels of sperm competition. We find evidence of positive selection in the protamine 2 gene in the species with the highest inferred levels of sperm competition. In addition, sperm competition levels across all species are strongly associated with high divergence in protamine 2 promoters that, in turn, are associated with sperm swimming speed. We suggest that changes in protamine 2 promoters are likely to enhance sperm swimming speed by making sperm heads more hydrodynamic. Such phenotypic changes are adaptive because sperm swimming speed may be a major determinant of fertilization success under sperm competition. Thus, when species have diverged recently, few changes in gene-coding sequences are found, while high divergence in promoters seems to be associated with the intensity of sexual selection.</p>},
	keywords = {Adaptation, positive selection, sperm competition},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=19364735},
	author = {Martin-Coello, J. and H. Dopazo and Arbiza, L. and Ausio, J. and Roldan, E. R. and Gomendio, M.}
}
@article {16584746,
	title = {Selective pressures at a codon-level predict deleterious mutations in human disease genes},
	journal = {J Mol Biol},
	volume = {358},
	number = {5},
	year = {2006},
	note = {Arbiza, Leonardo Duchi, Serena Montaner, David Burguet, Jordi Pantoja-Uceda, David Pineda-Lucena, Antonio Dopazo, Joaquin Dopazo, Hernan Research Support, Non-U.S. Gov{\textquoteright}t England Journal of molecular biology J Mol Biol. 2006 May 19;358(5):1390-404. Epub 2006 Mar 15.},
	pages = {1390-404},
	abstract = {Deleterious mutations affecting biological function of proteins are constantly being rejected by purifying selection from the gene pool. The non-synonymous/synonymous substitution rate ratio (omega) is a measure of selective pressure on amino acid replacement mutations for protein-coding genes. Different methods have been developed in order to predict non-synonymous changes affecting gene function. However, none has considered the estimation of selective constraints acting on protein residues. Here, we have used codon-based maximum likelihood models in order to estimate the selective pressures on the individual amino acid residues of a well-known model protein: p53. We demonstrate that the number of residues under strong purifying selection in p53 is much higher than those that are strictly conserved during the evolution of the species. In agreement with theoretical expectations, residues that have been noted to be of structural relevance, or in direct association with DNA, were among those showing the highest signals of purifying selection. Conversely, those changing according to a neutral, or nearly neutral mode of evolution, were observed to be irrelevant for protein function. Finally, using more than 40 human disease genes, we demonstrate that residues evolving under strong selective pressures (omega<0.1) are significantly associated (p<0.01) with human disease. We hypothesize that non-synonymous change on amino acids showing omega<0.1 will most likely affect protein function. The application of this evolutionary prediction at a genomic scale will provide an a priori hypothesis of the phenotypic effect of non-synonymous coding single nucleotide polymorphisms (SNPs) in the human genome.},
	keywords = {Amino Acid Sequence Amino Acid Substitution Codon/*genetics Databases, Genetic Evolution, Genetic Models, Human Humans Models, Inborn/*genetics Genome, Molecular Genes, Molecular Molecular Sequence Data *Mutation Neoplasms/genetics Proteins/genetics *Selection (Genetics) Tumor Suppressor Protein p53/chemistry/genetics, p53 Genetic Diseases},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=16584746},
	author = {Arbiza, L. and Duchi, S. and Montaner, D. and Burguet, J. and Pantoja-Uceda, D. and Pineda-Lucena, A. and Dopazo, J. and H. Dopazo}
}
