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While many studies of cis-elements CArG bound by serum response factor (SRF) are in progress, little is known about the positional distribution of the functional CArG elements around the transcription start site (TSS) of genes that they influence. We use a validated CArG data set to calculate the distance distribution of functional CArG elements around the TSS. Distances between adjacent CArGs were also analyzed. We compare these distributions with those derived using a control set of randomly selected CArGs (that were not experimentally validated for function). Our results show that most functional CArG elements (108 of 152, 71%) exist upstream of the annotated TSS, with copy number increasing as one moves closer to the TSS. Moreover, the average number of the CArG elements in the CArG-containing genes is significantly more than that in the control genes. Our study extends earlier bioinformatic analyses of functional CArG elements and provides an application of comparative sequence data to the identification of transcription factor binding sites. Key words: CArG elements, cis-elements, positional distribution, TSS, bioinformatics, mouse genome. Bien que plusieurs etudes soient en cours sur les boites cis CArG sur lesquelles se lie le facteur de reponse au serum (SRF), la distribution des boites CArG fonctionnelles autour des sites d'initiation de la transcription (TSS) des genes qu'ils regulent est peu connue. Les auteurs ont employe un jeu valide de boites CArG pour calculer la distribution des distances entre les boites CArG fonctionnelles et le TSS. Les distances entre boites CArG voisines ont egalement ete analysees. Les auteurs comparent ces distributions a celles obtenues en employant un jeu temoin constitue de boites CArG choisies aleatoirement (n'ayant pas ete validees experimentalement pour leur fonction). Les resultats montrent que la plupart des boites CArG fonctionnelles (108 de 152, 71%) sont situees en amont du TSS annote et que le nombre de copies augmente plus on se rapproche du TSS. De plus, le nombre moyen de boites CArG au sein de genes qui comptent de tels elements est significativement plus eleve que chez les temoins. Cette etude s'inscrit dans la suite d'analyses bioinformatiques anterieures sur les boites CArG fonctionnelles et fournit un exemple de l'utilisation d'une analyse comparee de sequences pour l'identification de sites de liaison de facteurs de transcription. Mots-cles : boites CArG, elements cis, distribution de position, TSS, bioinformatique, genome de la souris. [Traduit par la Redaction], Introduction One strong picture emerging from whole-genome sequencing in humans and model organisms is that noncoding DNA makes up the majority of most eukaryotic genomes. Noncoding regions in the DNA [...]

Newly emerging data from genome sequencing projects suggest that gene duplication, often accompanied by genetic map changes, is a common and ongoing feature of all genomes. This raises the possibility that differential expansion/contraction of various genomic sequences may be just as important a mechanism of phenotypic evolution as changes at the nucleotide level. However, the population-genetic mechanisms responsible for the success vs. failure of newly arisen gene duplicates are poorly understood. We examine the influence of various aspects of gene structure, mutation rates, degree of linkage, and population size (N) on the joint fate of a newly arisen duplicate gene and its ancestral locus. Unless there is active selection against duplicate genes, the probability of permanent establishment of such genes is usually no less than 1/(4N) (half of the neutral expectation), and it can be orders of magnitude greater if neofunctionalizing mutations are common. The probability of a map change (reassignment of a key function of an ancestral locus to a new chromosomal location) induced by a newly arisen duplicate is also generally >1/(4N) for unlinked duplicates, suggesting that recurrent gene duplication and alternative silencing may be a common mechanism for generating microchromosomal rearrangements responsible for postreproductive isolating barriers among species. Relative to subfunctionalization, neofunctionalization is expected to become a progressively more important mechanism of duplicate-gene preservation in populations with increasing size. However, even in large populations, the probability of neofunctionalization scales only with the square of the selective advantage. Tight linkage also influences the probability of duplicate-gene preservation, increasing the probability of subfunctionalization but decreasing the probability of neofunctionalization.