Structural wrinkles and the genomic regulatory sites of eukaryotes

Summary Calculations of DNA angular parameters in 50 eukaryotic sequences reveal regions of large conformational deviations from ideal DNA around regulatory sites. Frequently, discrete peaks of structural variation are present upstream of genes. Known regulatory regions often include variants of consensus sequences. Thus, imprecise sequences and structures are recognized within large genomic stretches. The existence of structurally wrinkled regions in the vicinity of regulatory sequences is likely to facilitate greatly their recognition by proteins and enzymes.     

Synorth: exploring the evolution of synteny and long-range regulatory interactions in vertebrate genomes

Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, often immobilizing other, unrelated genes into long-lasting syntenic arrangements. Synorth is a web resource for exploring and categorizing the syntenic relationships in genomic regulatory blocks across multiple genomes, tracing their evolutionary fate after teleost whole genome duplication at the level of genomic regulatory block loci, individual genes, and their phylogenetic context.     

A Bayesian method for finding regulatory segments in DNA

A goal of the human genome project is to determine the entire sequence of DNA (3 x 10(9) base pairs) found in chromosomes. The massive amounts of data produced by this project require interpretation. A Bayesian model is developed for locating regulatory regions in a DNA sequence. Regulatory regions are areas of DNA to which specific proteins bind and control whether or not a gene is transcribed to produce templates for protein synthesis. Each human cell contains the same DNA sequence. Thus the particular function of different cells is determined by the genes that are transcribed in that cell. A Hidden Markov chain is used to model whether a small interval of the DNA is in a regulatory region or not. This can be regarded as a changepoint problem where the changepoints are the start of a regulatory or nonregulatory region. The data consists of protein-binding elements, which are short subsequences, or "words," in the DNA sequence. Although these words can occur anywhere in the sequence, a larger number are expected in regulatory regions. Therefore, regulatory regions are detected by locating clusters of words. For a particular DNA sequence, the model automatically selects those words that best predict regions of interest. Markov chain Monte Carlo methods are used to explore the posterior distribution of the Hidden Markov chain. The model is tested by means of simulations, and applied to several DNA sequences.     

Origin of a substantial fraction of human regulatory sequences from transposable elements

Transposable elements (TEs) are abundant in mammalian genomes and have potentially contributed to their hosts' evolution by providing novel regulatory or coding sequences. We surveyed different classes of regulatory region in the human genome to assess systematically the potential contribution of TEs to gene regulation. Almost 25% of the analyzed promoter regions contain TE-derived sequences, including many experimentally characterized cis-regulatory elements. Scaffold/matrix attachment regions (S/MARs) and locus control regions (LCRs) that are involved in the simultaneous regulation of multiple genes also contain numerous TE-derived sequences. Thus, TEs have probably contributed substantially to the evolution of both gene-specific and global patterns of human gene regulation.     

The molecular population genetics of regulatory genes

Regulatory loci, which may encode both trans acting proteins as well as cis acting promoter regions, are crucial components of an organism's genetic architecture. Although evolution of these regulatory loci is believed to underlie the evolution of numerous adaptive traits, there is little information on natural variation of these genes. Recent molecular population genetic studies, however, have provided insights into the extent of natural variation at regulatory genes, the evolutionary forces that shape them and the phenotypic effects of molecular regulatory variants. These recent analyses suggest that it may be possible to study the molecular evolutionary ecology of regulatory diversification by examining both the extent and patterning of regulatory gene diversity, the phenotypic effects of molecular variation at these loci and their ecological consequences.