title: Patterns of variation in DNA segments upstream of transcription start sites.
abstract: It is likely that evolutionary differences among species are driven by sequence changes in regulatory regions. Likewise, polymorphisms in the promoter regions may be responsible for interindividual differences at the level of populations. We present an unbiased survey of genetic variation in 2-kb segments upstream of the transcription start sites of 28 protein-coding genes, characterized in five population groups of different geographic origin. On average, we found 9.1 polymorphisms and 8.8 haplotypes per segment with corresponding nucleotide and haplotype diversities of 0.082% and 58%, respectively. We characterized these segments through different summary statistics, Hardy-Weinberg equilibria fixation index (Fst) estimates, and neutrality tests, as well as by analyzing the distributions of haplotype allelic classes, introduced here to assess the departure from neutrality and examined by coalescent simulations under a simple population model, assuming recombinations or different demography. Our results suggest that genetic diversity in some of these regions could have been shaped by purifying selection and driven by adaptive changes in the other, thus explaining the relatively large variance in the corresponding genetic diversity indices loci. However, some of these effects could be also due to linkage with surrounding sequences, and the neutralists' explanations cannot be ruled out given uncertainty in the underlying demographic histories and the possibility of random effects due to the small size of the studied segments.
authors.affiliation: Centre de Recherche, Hôpital Sainte-Justine, Montréal, Quebec, Canada. damian.labuda@umontreal.ca
authors.forename: Damian
authors.initials: D
authors.lastname: Labuda
authors.forename: Catherine
authors.initials: C
authors.lastname: Labbé
authors.forename: Sylvie
authors.initials: S
authors.lastname: Langlois
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Lefebvre
authors.forename: Virginie
authors.initials: V
authors.lastname: Freytag
authors.forename: Claudia
authors.initials: C
authors.lastname: Moreau
authors.forename: Jakub
authors.initials: J
authors.lastname: Sawicki
authors.forename: Patrick
authors.initials: P
authors.lastname: Beaulieu
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
mesh_terms: D000483:Alleles; D000818:Animals; D004247:DNA / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D004247:DNA