Abstract:
:Measuring natural selection on genomic elements involved in the cis-regulation of gene expression--such as transcriptional enhancers and promoters--is critical for understanding the evolution of genomes, yet it remains a major challenge. Many studies have attempted to detect positive or negative selection in these noncoding elements by searching for those with the fastest or slowest rates of evolution, but this can be problematic. Here, we introduce a new approach to this issue, and demonstrate its utility on three mammalian transcriptional enhancers. Using results from saturation mutagenesis studies of these enhancers, we classified all possible point mutations as upregulating, downregulating, or silent, and determined which of these mutations have occurred on each branch of a phylogeny. Applying a framework analogous to Ka/Ks in protein-coding genes, we measured the strength of selection on upregulating and downregulating mutations, in specific branches as well as entire phylogenies. We discovered distinct modes of selection acting on different enhancers: although all three have experienced negative selection against downregulating mutations, the selection pressures on upregulating mutations vary. In one case, we detected positive selection for upregulation, whereas the other two had no detectable selection on upregulating mutations. Our methodology is applicable to the growing number of saturation mutagenesis data sets, and provides a detailed picture of the mode and strength of natural selection acting on cis-regulatory elements.
journal_name
Mol Biol Evoljournal_title
Molecular biology and evolutionauthors
Smith JD,McManus KF,Fraser HBdoi
10.1093/molbev/mst134subject
Has Abstractpub_date
2013-11-01 00:00:00pages
2509-18issue
11eissn
0737-4038issn
1537-1719pii
mst134journal_volume
30pub_type
杂志文章abstract::While it is widely accepted that most animals (Metazoa) do not have endogenous cellulases, relying instead on intestinal symbionts for cellulose digestion, the glycosyl hydrolase family 9 (GHF9) cellulases found in the genomes of termites, abalone, and sea squirts could be an exception. Using information from expresse...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msi107
更新日期:2005-05-01 00:00:00
abstract::Male reproductive fitness is strongly affected by seminal fluid. In addition to interacting with the female environment, seminal fluid mediates important physiological characteristics of sperm, including capacitation and motility. In mammals, the male reproductive tract shows a striking degree of compartmentalization,...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msp094
更新日期:2009-08-01 00:00:00
abstract::The proportion of functional sequence in the human genome is currently a subject of debate. The most widely accepted figure is that approximately 5% is under purifying selection. In Drosophila, estimates are an order of magnitude higher, though this corresponds to a similar quantity of sequence. These estimates depend...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msp299
更新日期:2010-04-01 00:00:00
abstract::We propose an improved version of the neighbor-joining (NJ) algorithm of Saitou and Nei. This new algorithm, BIONJ, follows the same agglomerative scheme as NJ, which consists of iteratively picking a pair of taxa, creating a new mode which represents the cluster of these taxa, and reducing the distance matrix by repl...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a025808
更新日期:1997-07-01 00:00:00
abstract::Drosophila melanogaster is widely used as a model in DNA variation studies. Patterns of polymorphism have, however, been affected by the history of this species, which is thought to have recently spread out of Africa to the rest of the world. We analyzed DNA sequence variation in 11 populations, including four contine...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msh089
更新日期:2004-08-01 00:00:00
abstract::To explain why informational genes (i.e., those involved in transcription, translation, and related processes) are less likely than housekeeping genes to be horizontally transferred, Jain and coworkers proposed the complexity hypothesis. The underlying idea is that informational genes belong to large, complex systems ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msi006
更新日期:2005-02-01 00:00:00
abstract::Polyploidization events have occurred during the evolution of many fungi, plant, and animal species and are thought to contribute to speciation and tumorigenesis, however little is known about how ploidy level contributes to adaptation at the molecular level. Here we integrate whole genome sequencing, RNA expression a...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msx205
更新日期:2017-10-01 00:00:00
abstract::There are three common alleles (A, B, and O) at the human ABO blood group locus. We compared nucleotide sequences of these alleles, and relatively large numbers of nucleotide differences were found among them. These differences correspond to the divergence time of at least a few million years, which is unusually large...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a025776
更新日期:1997-04-01 00:00:00
abstract::Mitochondrial transcription factor B (mtTFB), an essential component in regulating the expression of mitochondrial DNA-encoded genes in both yeast and humans, is a dimethyladenosine methyltransferase (DMT) that has acquired a secondary role in mitochondrial transcription. So far, mtTFB has only been well studied in Op...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msk001
更新日期:2006-06-01 00:00:00
abstract::It is known that the effective population size (Ne) and the mutation rate (u) vary across the genome. Here, we show that ignoring this heterogeneity may lead to biased estimates of past demography. To solve the problem, we develop new methods for jointly inferring past changes in population size and detecting variatio...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msy212
更新日期:2019-02-01 00:00:00
abstract::Genetic incompatibilities are commonly observed between hybridizing species. Although this type of isolating mechanism has received considerable attention, we have few examples describing how genetic incompatibilities evolve. We investigated the evolution of two loci involved in a classic example of a Bateson-Dobzhans...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/mst127
更新日期:2013-10-01 00:00:00
abstract::Flowering time is one of the key determinants of crop adaptation to local environments during domestication. However, the genetic basis underlying flowering time is yet to be elucidated in most cereals. Although staple cereals, such as rice, maize, wheat, barley, and sorghum, have spread and adapted to a wide range of...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msv148
更新日期:2015-10-01 00:00:00
abstract::Human DNA variation is currently a subject of intense research because of its importance for studying human origins, evolution, and demographic history and for association studies of complex diseases. A approximately 10-kb region on chromosome 1, which contains only four small exons (each <155 bp), was sequenced for 6...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a003795
更新日期:2001-02-01 00:00:00
abstract::Homeobox genes encode transcription factors involved in many aspects of developmental processes. The homeodomain-leucine zipper (HD-Zip) genes, which are characterized by the presence of both a homeodomain and a leucine zipper motif, form a clade within the homeobox superfamily and were previously reported only from v...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a003828
更新日期:2001-04-01 00:00:00
abstract::Polymerases are essential for life, being responsible for replication, transcription, and the repair of nucleic acid molecules. Those that share a right-hand-shaped fold and catalytic site structurally similar to the DNA polymerase I of Escherichia coli may catalyze RNA- or DNA-dependent RNA polymerization, reverse tr...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msu219
更新日期:2014-10-01 00:00:00
abstract::The distribution of fitness effects of mutations is a factor of fundamental importance in evolutionary biology. We determined the distribution of fitness effects of 510 mutants that each carried between 1 and 10 mutations (synonymous and nonsynonymous) in the hisA gene, encoding an essential enzyme in the l-histidine ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msx325
更新日期:2018-03-01 00:00:00
abstract::During the course of a random sequencing project of the genome of the dimorphic yeast Yarrowia lipolytica, we have identified sequences that were repeated in the genome and that matched the reverse transcriptase (RT) sequence of non-long terminal repeat (non-LTR) retrotransposons. Extension of sequencing on each side ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a004125
更新日期:2002-05-01 00:00:00
abstract::Cysteine-rich secretory proteins (CRISPs) are glycoproteins found exclusively in vertebrates and have broad diversified functions. They are hypothesized to play important roles in mammalian reproduction and in reptilian venom, where they disrupt homeostasis of the prey through several mechanisms, including among other...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/mss058
更新日期:2012-07-01 00:00:00
abstract::Some genes have repeatedly been found to control diverse adaptations in a wide variety of organisms. Such gene reuse reveals not only the diversity of phenotypes these unique genes control but also the composition of developmental gene networks and the genetic routes available to and taken by organisms during adaptati...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msz194
更新日期:2019-12-01 00:00:00
abstract::Wolbachia bacteria infect about half of all arthropods, with diverse and extreme consequences ranging from sex-ratio distortion and mating incompatibilities to protection against viruses. These phenotypic effects, combined with efficient vertical transmission from mothers to offspring, satisfactorily explain the invas...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msx073
更新日期:2017-05-01 00:00:00
abstract::Empirical codon models (ECMs) estimated from a large number of globular protein families outperformed mechanistic codon models in their description of the general process of protein evolution. Among other factors, ECMs implicitly model the influence of amino acid properties and multiple nucleotide substitutions (MNS)....
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/mss266
更新日期:2013-03-01 00:00:00
abstract::Due to its speed, the distance approach remains the best hope for building phylogenies on very large sets of taxa. Recently (R. Desper and O. Gascuel, J. Comp. Biol. 9:687-705, 2002), we introduced a new "balanced" minimum evolution (BME) principle, based on a branch length estimation scheme of Y. Pauplin (J. Mol. Evo...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msh049
更新日期:2004-03-01 00:00:00
abstract::Computational tools with a balanced sensitivity and specificity in identification of candidate cancer drivers are highly desired. In this study, we propose a new statistical test, namely the dJ/dS ratio test, to compute the relative mutation rate of exon/intron junction sites (dJ) to synonymous sites (dS); observation...
journal_title:Molecular biology and evolution
pub_type: 信件
doi:10.1093/molbev/msv083
更新日期:2015-08-01 00:00:00
abstract::Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200-4,100 m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome o...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msv071
更新日期:2015-07-01 00:00:00
abstract::Phenotypic evolution may occur either through alterations to the structure of protein-coding genes or their expression. Evidence for which of these two mechanisms more commonly contribute to the evolution of a phenotype can be garnered from examples of parallel and convergent evolution. The visual system of East Afric...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msq171
更新日期:2010-12-01 00:00:00
abstract::Patterns of population structure provide insights into evolutionary processes and help identify groups of individuals for genotype-phenotype association studies. With increasing availability of polymorphic molecular markers across genomes, the examination of population structure using large numbers of unlinked loci ha...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msp052
更新日期:2009-06-01 00:00:00
abstract::Ecological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or "specialized" metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and cha...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msaa122
更新日期:2020-10-01 00:00:00
abstract::Because they represent the earliest divergences of the Chlorophyta and include the smallest known eukaryotes (e.g., the coccoid Ostreococcus), the morphologically diverse unicellular green algae making up the Prasinophyceae are central to our understanding of the evolutionary patterns that accompanied the radiation of...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msn285
更新日期:2009-03-01 00:00:00
abstract::Numerous studies have used indices of genetic distance between species to reconstruct evolutionary relationships and to estimate divergence time. However, the empirical relationship between molecular-based indices of genetic divergence and divergence time based on the fossil record is poorly known. To date, the result...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a040651
更新日期:1991-05-01 00:00:00
abstract::The giant extracellular hexagonal bilayer hemoglobin (HBL-Hb) of the deep-sea hydrothermal vent tube worm Riftia pachyptila is able to transport simultaneously O(2) and H(2)S in the blood from the gills to a specific organ: the trophosome that harbors sulfide-oxidizing endosymbionts. This vascular HBL-Hb is made of 14...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a004205
更新日期:2002-09-01 00:00:00