Abstract：
:Biological evolution generates a surprising amount of site-specific variability in protein sequences. Yet, attempts at modeling this process have been only moderately successful, and current models based on protein structural metrics explain, at best, 60% of the observed variation. Surprisingly, simple measures of protein structure, such as solvent accessibility, are often better predictors of site-specific variability than more complex models employing all-atom energy functions and detailed structural modeling. We suggest here that these more complex models perform poorly because they lack consideration of the evolutionary process, which is, in part, captured by the simpler metrics. We compare protein sequences that are computationally designed to sequences that are computationally evolved using the same protein-design energy function and to homologous natural sequences. We find that, by a wide variety of metrics, evolved sequences are much more similar to natural sequences than are designed sequences. In particular, designed sequences are too conserved on the protein surface relative to natural sequences, whereas evolved sequences are not. Our results suggest that evolutionary simulation produces a realistic sampling of sequence space. By contrast, protein design-at least as currently implemented-does not. Existing energy functions seem to be sufficiently accurate to correctly describe the key thermodynamic constraints acting on protein sequences, but they need to be paired with realistic sampling schemes to generate realistic sequence alignments.
journal_name
Geneticsjournal_title
Geneticsauthors
Jiang Q,Teufel AI,Jackson EL,Wilke COdoi
10.1534/genetics.118.300699subject
Has Abstractpub_date
2018-04-01 00:00:00pages
1387-1395issue
4eissn
0016-6731issn
1943-2631pii
genetics.118.300699journal_volume
208pub_type
杂志文章相关文献
GENETICS文献大全abstract：:The gastrulation defective (gd) locus encodes a novel serine protease that is involved in specifying the dorsal-ventral axis during embryonic development. Mutant alleles of gd have been classified into three complementation groups, two of which exhibit strong interallelic (intragenic) complementation. To understand th...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:To understand the in vivo function of the unique and conserved carboxy-terminal repeat domain (CTD) of RNA polymerase II largest subunit (RpII215), we have studied RNA polymerase II biosynthesis, activity and genetic function in Drosophila RpII215 mutants that possessed all (C4), half (W81) or none (IIt) of the CTD re...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:We analyze nucleotide polymorphism data for a large number of loci in areas of normal to high recombination in Drosophila melanogaster and D. simulans (24 and 16 loci, respectively). We find a genome-wide, systematic departure from the neutral expectation for a panmictic population at equilibrium in natural population...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:Drosophila adult leg development provides an ideal model system for characterizing the molecular mechanisms of hormone-triggered morphogenesis. A pulse of the steroid hormone ecdysone at the onset of metamorphosis triggers the rapid transformation of a flat leg imaginal disc into an immature adult leg, largely through...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：2003-11-01 00:00:00
abstract：:Drosophila melanogaster, an ancestrally African species, has recently spread throughout the world, associated with human activity. The species has served as the focus of many studies investigating local adaptation relating to latitudinal variation in non-African populations, especially those from the United States and...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.114.161463
更新日期：2014-05-01 00:00:00
abstract：:Scans of the human genome have identified many loci as potential targets of recent selection, but exploration of these candidates is required to verify the accuracy of genomewide scans and clarify the importance of adaptive evolution in recent human history. We present analyses of one such candidate, enamelin, whose p...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.107.077123
更新日期：2008-03-01 00:00:00
abstract：:In yeast, 17 histidine-requiring mutants derived from and interallelically complementary to his1-7 were analyzed. The genetic basis of the complementation response was elucidated by mitotic and meiotic gene conversion. Each allele probably carries an unaltered 7-site mutation and a unique second-site alteration. The s...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1978-11-01 00:00:00
abstract：:Electrophoretic comparisons of 40S and 55S ribosomal subunit proteins from 18 strains of Drosophila melanogaster revealed the virtual absence of allelic variation. More detailed two-dimensional studies on the large subunit proteins in 6 of the strains demonstrated additional complexity but still no interstrain variati...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1974-12-01 00:00:00
abstract：:The Saccharomyces cerevisiae mitochondrial endonuclease I-SceI creates a double-strand break as the initiating step in the gene conversional transfer of the omega+ intron to omega- DNA. We have expressed a galactose-inducible synthetic I-SceI gene in the nucleus of yeast that also carries the I-SceI recognition site o...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:The spatial model of Levene (1953) was examined in a finite population and compared to a temporal model. The spatial model was much more effective in retaining genetic variation in a finite population. Furthermore, the haploid spatial model was more effective in retaining genetic variation than the analogous diploid a...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1978-06-01 00:00:00
abstract：:An elevated mutation rate can provide cells with a source of mutations to adapt to changing environments. We identified a negative epistatic interaction involving naturally occurring variants in the MLH1 and PMS1 mismatch repair (MMR) genes of Saccharomyces cerevisiae We hypothesized that this MMR incompatibility, cre...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.116.199513
更新日期：2017-04-01 00:00:00
abstract：:bld2-1 mutant Chlamydomonas reinhardtii strains assemble basal bodies with singlet microtubules; bld2-1 cells display flagellar assembly defects as well as positioning defects of the mitotic spindle and cleavage furrow. To further understand the role of the BLD2 gene, we have isolated three new bld2 alleles and three ...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:During selection for protein content in mice at the Technical University of Berlin, individuals showing high protein content and a compact exterior were noted. Animals showing this "Compact" phenotype were separated to form a new line. The present investigations were carried out on a Hungarian subpopulation of this li...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:We examined linkage relationships for RecBC-mediated recombination in lytic cycle crosses of lambda phages bearing two cohesive end sites (cos) oriented in the same direction. The relationships obtained imply that a given recombinant tends to be packaged from the cos site that is the nearer one to the right of the exc...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:Genetic divergence in the form of the mandible is examined in ten inbred strains of mice. Several univariate and multivariate genetic distance estimates are given for the morphological data and these estimates are compared to measures of genealogical and molecular divergence. Highly significant divergence occurs among...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:Microsatellites are tandemly repeated short DNA sequences that are favored as molecular-genetic markers due to their high polymorphism index. Plant genomes characterized to date exhibit taxon-specific differences in frequency, genomic location, and motif structure of microsatellites, indicating that extant microsatell...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.105.054791
更新日期：2006-04-01 00:00:00
abstract：:Parentage analysis is an important method that is used widely in zoological and ecological studies. Current mathematical models of parentage analyses usually assume that a population has a uniform genetic structure and that mating is panmictic. In a natural population, the geographic or social structure of a populatio...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.118.301592
更新日期：2018-12-01 00:00:00
abstract：:One of the most important parameters in population genetics is theta = 4Ne mu where Ne is the effective population size and mu is the rate of mutation per gene per generation. We study two related problems, using the maximum likelihood method and the theory of coalescence. One problem is the potential improvement of a...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:Preliminary studies with restriction fragment length polymorphisms of mitochondrial DNA (mtDNA) in natural populations of Drosophila melanogaster revealed considerable variation in terms of nucleotide sequence and overall size. In this report we present data from more isofemale lines and more restriction enzymes, and ...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:Centromeres control chromosome inheritance in eukaryotes, yet their DNA structure and primary sequence are hypervariable. Most animals and plants have megabases of tandem repeats at their centromeres, unlike yeast with unique centromere sequences. Centromere function requires the centromere-specific histone CENH3 (CEN...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.110.120337
更新日期：2010-10-01 00:00:00
abstract：:Conspicuous differences in floral morphology are partly responsible for reproductive isolation between two sympatric species of monkeyflower because of their effect on visitation of the flowers by different pollinators. Mimulus lewisii flowers are visited primarily by bumblebees, whereas M. cardinalis flowers are visi...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate stimulus-dependent activation of cognate heterotrimeric G-proteins, triggering ensuing downstream cellular responses. Tight regulation of GPCR-evoked pathways is required because prolonged stimulation can be detrimental to an organism. St...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.115.186122
更新日期：2016-05-01 00:00:00
abstract：:The recessive mutation, hop1-1, was isolated by use of a screen designed to detect mutations defective in homologous chromosomal pairing during meiosis in Saccharomyces cerevisiae. Mutants in HOP1 displayed decreased levels of meiotic crossing over and intragenic recombination between markers on homologous chromosomes...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：:Mitotic cell divisions increase cell number while faithfully distributing the replicated genome at each division. The Caenorhabditis elegans embryo is a powerful model for eukaryotic cell division. Nearly all of the genes that regulate cell division in C. elegans are conserved across metazoan species, including humans...
journal_title：Genetics
pub_type： 杂志文章,评审
doi：10.1534/genetics.118.301367
更新日期：2019-01-01 00:00:00
abstract：:The human fungal pathogen Candida albicans can reversibly switch between two cell types named "white" and "opaque," each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A hi...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.116.190645
更新日期：2016-08-01 00:00:00
abstract：:Interactions between Drosophila C virus (DCV) and its natural host, Drosophila melanogaster, were investigated using 15 geographical population samples infected by intraabdominal inoculation. These strains derived from natural populations of D. melanogaster differed in susceptibility to the DCVc. One strain was "parti...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:Thirty-five nucleotide polymorphisms were found in a 21.5-kbp region including the Est6 locus among 42 isoallelic lines extracted from a single natural population of Drosophila melanogaster. The heterozygosity per nucleotide pair was estimated to be 0.010 overall, but was lower in sequences hybridizing to transcripts ...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Mutants of Paramecium caudatum with abnormal swimming behavior or responses to cations were obtained by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Some of the mutants, like pawn in P. tetraurelia, cannot swim backward and are called CNR. Seven independently obtained CNR mutants belonged to three complement...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
abstract：:Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable expressivity of traits. Although quantitative trait locus (QTL) analysis has been a powerful tool for localizing the ...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.108.090175
更新日期：2008-12-01 00:00:00
abstract：:Predicting the chromosomal location of mapped markers has been difficult because linkage maps do not reveal differences in crossover frequencies along the physical structure of chromosomes. Here we combine a physical crossover map based on the distribution of recombination nodules (RNs) on Solanum lycopersicum (tomato...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.107.074138
更新日期：2007-08-01 00:00:00
