Abstract:
:Selection on phenotypes may cause genetic change. To understand the relationship between phenotype and gene expression from an evolutionary viewpoint, it is important to study the concordance between gene expression and profiles of phenotypes. In this study, we use a novel method of clustering to identify genes whose expression profiles are related to a quantitative phenotype. Cluster analysis of gene expression data aims at classifying genes into several different groups based on the similarity of their expression profiles across multiple conditions. The hope is that genes that are classified into the same clusters may share underlying regulatory elements or may be a part of the same metabolic pathways. Current methods for examining the association between phenotype and gene expression are limited to linear association measured by the correlation between individual gene expression values and phenotype. Genes may be associated with the phenotype in a nonlinear fashion. In addition, groups of genes that share a particular pattern in their relationship to phenotype may be of evolutionary interest. In this study, we develop a method to group genes based on orthogonal polynomials under a multivariate Gaussian mixture model. The effect of each expressed gene on the phenotype is partitioned into a cluster mean and a random deviation from the mean. Genes can also be clustered based on a time series. Parameters are estimated using the expectation-maximization algorithm and implemented in SAS. The method is verified with simulated data and demonstrated with experimental data from 2 studies, one clusters with respect to severity of disease in Alzheimer's patients and another clusters data for a rat fracture healing study over time. We find significant evidence of nonlinear associations in both studies and successfully describe these patterns with our method. We give detailed instructions and provide a working program that allows others to directly implement this method in their own analyses.
journal_name
Mol Biol Evoljournal_title
Molecular biology and evolutionauthors
Qu Y,Xu Sdoi
10.1093/molbev/msl019subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1558-73issue
8eissn
0737-4038issn
1537-1719pii
msl019journal_volume
23pub_type
杂志文章abstract::The capacity to biomineralize is closely linked to the rapid expansion of animal life during the early Cambrian, with many skeletonized phyla first appearing in the fossil record at this time. The appearance of disparate molluscan forms during this period leaves open the possibility that shells evolved independently a...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msp278
更新日期:2010-03-01 00:00:00
abstract::The structural genes for nitrogenase, nifK, nifD, and nifH, are crucial for nitrogen fixation. Previous phylogenetic analysis of the amino acid sequence of nifH suggested that this gene had been horizontally transferred from a proteobacterium to the gram-positive/cyanobacterial clade, although the confounding effects ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a040184
更新日期:1995-01-01 00:00:00
abstract::A simple model for the evolution of the rate of molecular evolution is presented. With a Bayesian approach, this model can serve as the basis for estimating dates of important evolutionary events even in the absence of the assumption of constant rates among evolutionary lineages. The method can be used in conjunction ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a025892
更新日期:1998-12-01 00:00:00
abstract::Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39), the most abundant protein in nature, catalyzes the assimilation of CO(2) (worldwide about 10(11) t each year) by carboxylation of ribulose-1,5-bisphosphate. It is a hexadecamer consisting of eight large and eight small subunits. Although the Rubis...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msr008
更新日期:2011-06-01 00:00:00
abstract::The quantitative immunological technique of micro-complement fixation (MC'F) has been routinely used during the past decade to assess evolutionary relationships among living vertebrate species. The large data base that has been generated, along with the excellent correlations between immunologically measured genetic d...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a040405
更新日期:1986-09-01 00:00:00
abstract::Bacterial plasmids substantially contribute to the rapid spread of antibiotic resistance, which is a crisis in healthcare today. Coevolution of plasmids and their hosts promotes this spread of resistance by ameliorating the cost of plasmid carriage. However, our knowledge of plasmid-bacteria coevolution is solely base...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msaa024
更新日期:2020-06-01 00:00:00
abstract::This paper concludes that the statistical properties of protein evolution are compatible with a particular model of evolution by natural selection. The argument begins with a statistical description of the molecular clock based on a Poisson process with a randomly varying tick rate. If the time scale of the change of ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a040382
更新日期:1986-03-01 00:00:00
abstract::The Sp family of transcription factors binds GC-rich DNA sequences. The ubiquitously expressed Sp1 and Sp3 have been well characterized in mammals. Presented here is the characterization of the only Sp protein expressed in the liver or heart tissue of the teleost fish Fundulus heteroclitus. This protein, fSp3, is most...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a004074
更新日期:2002-03-01 00:00:00
abstract::Diverging from the classic paradigm of random gene order in eukaryotes, gene proximity can be leveraged to systematically identify functionally related gene neighborhoods in eukaryotes, utilizing techniques pioneered in bacteria. Current methods of identifying gene neighborhoods typically rely on sequence similarity t...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msaa221
更新日期:2021-01-23 00:00:00
abstract::Colias eurytheme butterflies display extensive allozyme polymorphism in the enzyme phosphoglucose isomerase (PGI). Earlier studies on biochemical and fitness effects of these genotypes found evidence of strong natural selection maintaining this polymorphism in the wild. Here we analyze the molecular features of this p...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msj062
更新日期:2006-03-01 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 pyrimidine exchange type of RNA editing in land plant (embryophyte) organelles has largely remained an enigma with respect to its biochemical mechanisms, the underlying specificities, and its raison d'être. Apparently arising with the earliest embryophytes, RNA editing is conspicuously absent in one clade of liver...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msn084
更新日期:2008-07-01 00:00:00
abstract::The human Y chromosome consists of ampliconic genes, which are located in palindromes and undergo frequent gene conversion, and single-copy genes including the primary sex-determining locus, SRY. Here, we demonstrate that SRY is duplicated in a large palindrome in the European rabbit (Oryctolagus cuniculus). Furthermo...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msq139
更新日期:2010-11-01 00:00:00
abstract::The phylogenetic relationships of the biflagellate protist group Apusomonadidae have been unclear despite the availability of some molecular data. We analyzed sequences from 6 nuclear encoded genes-small-subunit rRNA, large-subunit rRNA, alpha-tubulin, beta-tubulin, actin, and heat shock protein 90-to infer the phylog...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msl120
更新日期:2006-12-01 00:00:00
abstract::Length variation due to tandem repeats is now recognized as a common feature of animal mitochondrial DNA; however, the evolutionary dynamics of repeated sequences are not well understood. Using phylogenetic analysis, predictions of three models of repeat evolution were tested for arrays of 260-bp repeats in the cyprin...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a025728
更新日期:1997-12-01 00:00:00
abstract::Disturbances in the schedules of gene expression in developing interspecific fish hybrids have been used to draw inferences about the extent of gene regulatory divergence between species and about the degree to which this gene regulatory divergence is correlated with structural gene divergence, as estimated by genetic...
journal_title:Molecular biology and evolution
pub_type: 杂志文章,评审
doi:10.1093/oxfordjournals.molbev.a040349
更新日期:1985-05-01 00:00:00
abstract::Some of the assumptions underlying estimates of DNA and protein sequence divergence are examined. A solution for the variance of these estimates that allows for different mutation rates and different population sizes in each species and for an arbitrary structure in the initial population is obtained. It is shown that...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a040303
更新日期:1983-12-01 00:00:00
abstract::Finding correct species relationships using phylogeny reconstruction based on molecular data is dependent on several empirical and technical factors. These include the choice of DNA sequence from which phylogeny is to be inferred, the establishment of character homology within a sequence alignment, and the phylogeny a...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a026285
更新日期:2000-12-01 00:00:00
abstract::The nuclear large subunit (LSU) rRNA gene is a rich source of phylogenetic characters because of its large size, mosaic of slowly and rapidly evolving regions, and complex secondary structure variation. Nevertheless, many studies have indicated that inconsistency, bias, and gene-specific error (e.g., within-individual...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a003767
更新日期:2001-12-01 00:00:00
abstract::Here, we address a much-debated topic: is there or is there not an organismal tree of gamma-proteobacteria that can be unambiguously inferred from a core of shared genes? We apply several recently developed analytical methods to this problem, for the first time. Our heat map analyses of P values and of bootstrap bipar...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msj113
更新日期:2006-05-01 00:00:00
abstract::Standard methods of phylogenetic reconstruction are based on models that assume homogeneity of nucleotide composition among taxa. However, this assumption is often violated in biological data sets. In this study, we examine possible effects of nucleotide heterogeneity among lineages on the phylogenetic reconstruction ...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msi036
更新日期:2005-03-01 00:00:00
abstract::Molluscs in general, and bivalves in particular, exhibit an extraordinary degree of mitochondrial gene order variation when compared with other metazoans. Two factors inhibiting our understanding the evolution of gene rearrangement in bivalves are inadequate taxonomic sampling and failure to examine gene order in a ph...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msg218
更新日期:2003-11-01 00:00:00
abstract::Remarkably little is known about the population-level processes leading up to the extinction of the neandertal. To examine this, we use mitochondrial DNA sequences from 13 neandertal individuals, including a novel sequence from northern Spain, to examine neandertal demographic history. Our analyses indicate that recen...
journal_title:Molecular biology and evolution
pub_type: 信件
doi:10.1093/molbev/mss074
更新日期:2012-08-01 00:00:00
abstract::How is adaptability generated in a system composed of interacting cellular machineries, each with a separate and functionally critical job to perform? The machinery for organelle inheritance is precisely one such system, requiring coordination between robust and ancient cellular modules, including the cell cycle, cyto...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msr264
更新日期:2012-03-01 00:00:00
abstract::The level of DNA polymorphism in the ancestral species at the time of speciation can be estimated using DNA sequences from many loci sampled from 2 or more extant species. The comparison between ancestral and extant polymorphism can be informative about the population genetics of speciation. In this study, we collecte...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msm209
更新日期:2007-12-01 00:00:00
abstract::Plasticity and robustness of signaling pathways partly rely on genetic redundancy, although the precise mechanism that provides functional specificity to the different redundant elements in a given process is often unknown. In Arabidopsis, functional redundancy in gibberellin signaling has been largely attributed to t...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msq012
更新日期:2010-06-01 00:00:00
abstract::Examination of the genomic sequence of the telomere region makes it possible to understand the evolution of the structure of chromosomal ends. We compared the genomic sequences of 14 chromosomal ends of rice, Oryza sativa, L., on the basis of the variation in TTTAGGG repeats. In the proximal telomere repeats, nucleoti...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msm227
更新日期:2008-01-01 00:00:00
abstract::Although evolutionary studies of gene function often rely on RNA interference, the ideal approach would use reverse genetics to create null mutations for cross-species comparisons and forward genetics to identify novel genes in each species. We have used transcription activator-like effector nucleases (TALENs) to faci...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/mst213
更新日期:2014-02-01 00:00:00
abstract::Alpha-defensins are a family of mammalian antimicrobial peptides that exhibit variable activity against a panel of microbes, including bacteria, fungi, and enveloped viruses. We have employed a maximum-likelihood approach to detect evidence of positive selection (adaptive evolution) in the evolution of these important...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/molbev/msh084
更新日期:2004-05-01 00:00:00
abstract::Two longstanding issues on the molecular clock hypothesis are studied in this article. First, is there a global molecular clock in mammals? Although many authors have observed unequal rates of nucleotide substitution among mammalian lineages, some authors have proposed a global clock for all eutherians, i.e., a single...
journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a004043
更新日期:2002-12-01 00:00:00