Fitness Assays Reveal Incomplete Functional Redundancy of the HoxA1 and HoxB1 Paralogs of Mice.

Abstract:

:Gene targeting techniques have led to the phenotypic characterization of numerous genes; however, many genes show minimal to no phenotypic consequences when disrupted, despite many having highly conserved sequences. The standard explanation for these findings is functional redundancy. A competing hypothesis is that these genes have important ecological functions in natural environments that are not needed under laboratory settings. Here we discriminate between these hypotheses by competing mice (Mus musculus) whose Hoxb1 gene has been replaced by Hoxa1, its highly conserved paralog, against matched wild-type controls in seminatural enclosures. This Hoxb1(A1) swap was reported as a genetic manipulation resulting in no discernible embryonic or physiological phenotype under standard laboratory tests. We observed a transient decline in first litter size for Hoxb1(A1) homozygous mice in breeding cages, but their fitness was consistently and more dramatically reduced when competing against controls within seminatural populations. Specifically, males homozygous for the Hoxb1(A1) swap acquired 10.6% fewer territories and the frequency of the Hoxb1(A1) allele decreased from 0.500 in population founders to 0.419 in their offspring. The decrease in Hoxb1(A1) frequency corresponded with a deficiency of both Hoxb1(A1) homozygous and heterozygous offspring. These data suggest that Hoxb1 and Hoxa1 are more phenotypically divergent than previously reported and support that sub- and/or neofunctionalization has occurred in these paralogous genes leading to a divergence of gene function and incomplete redundancy. Furthermore, this study highlights the importance of obtaining fitness measures of mutants in ecologically relevant conditions to better understand gene function and evolution.

journal_name

Genetics

journal_title

Genetics

authors

Ruff JS,Saffarini RB,Ramoz LL,Morrison LC,Baker S,Laverty SM,Tvrdik P,Potts WK

doi

10.1534/genetics.115.178079

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

727-36

issue

2

eissn

0016-6731

issn

1943-2631

pii

201/2/727

journal_volume

201

pub_type

杂志文章

相关文献

GENETICS文献大全
  • Cytochemical studies on the problem of macronuclear subnuclei in tetrahymena.

    abstract::DNA amounts in macronuclei and micronuclei of Tetrahymena pyriformis were measured by Feulgen microspectrophotometry. Assuming that the unreplicated micronucleus is diploid, the unreplicated macronucleus was found to contain approximately 45 times the haploid DNA amount. The relationship of these findings to the 45 in...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Woodard J,Kaneshiro E,Gorovsky MA

    更新日期:1972-02-01 00:00:00

  • Mortality in the children of atomic bomb survivors and controls.

    abstract::A continuing study of mortality rates among children born to survivors of the atomic bombings and a suitable group of controls has been updated; the average interval between birth and verification of death or survival is 17 years. The mortality experience is now based on 18,946 children liveborn to parents one or both...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Neel JV,Kato H,Schull WJ

    更新日期:1974-02-01 00:00:00

  • Origin and diversification dynamics of self-incompatibility haplotypes.

    abstract::Self-incompatibility (SI) is a genetic system found in some hermaphrodite plants. Recognition of pollen by pistils expressing cognate specificities at two linked genes leads to rejection of self pollen and pollen from close relatives, i.e., to avoidance of self-fertilization and inbred matings, and thus increased outc...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.111.127399

    authors: Gervais CE,Castric V,Ressayre A,Billiard S

    更新日期:2011-07-01 00:00:00

  • Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres.

    abstract::While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellu...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.115.177360

    authors: Gent JI,Wang K,Jiang J,Dawe RK

    更新日期:2015-08-01 00:00:00

  • Distribution of retroelements in centromeres and neocentromeres of maize.

    abstract::Fluorescent in situ hybridization was used to examine the distribution of six abundant long terminal repeat (LTR) retroelements, Opie, Huck, Cinful-1, Prem-2/Ji, Grande, and Tekay/Prem-1 on maize pachytene chromosomes. Retroelement staining in euchromatin was remarkably uniform, even when we included the structurally ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Mroczek RJ,Dawe RK

    更新日期:2003-10-01 00:00:00

  • Resection activity of the Sgs1 helicase alters the affinity of DNA ends for homologous recombination proteins in Saccharomyces cerevisiae.

    abstract::The RecQ helicase family is critical during DNA damage repair, and mutations in these proteins are associated with Bloom, Werner, or Rothmund-Thompson syndromes in humans, leading to cancer predisposition and/or premature aging. In the budding yeast Saccharomyces cerevisiae, mutations in the RecQ homolog, SGS1, phenoc...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.113.157370

    authors: Bernstein KA,Mimitou EP,Mihalevic MJ,Chen H,Sunjaveric I,Symington LS,Rothstein R

    更新日期:2013-12-01 00:00:00

  • Sex-linked inheritance in macaque monkeys: implications for effective population size and dispersal to Sulawesi.

    abstract::Sex-specific differences in dispersal, survival, reproductive success, and natural selection differentially affect the effective population size (N(e)) of genomic regions with different modes of inheritance such as sex chromosomes and mitochondrial DNA. In papionin monkeys (macaques, baboons, geladas, mandrills, drill...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.110.116228

    authors: Evans BJ,Pin L,Melnick DJ,Wright SI

    更新日期:2010-07-01 00:00:00

  • P element-mediated in vivo deletion analysis of white-apricot: deletions between direct repeats are strongly favored.

    abstract::We have isolated and characterized deletions arising within a P transposon, P[hswa], in the presence of P transposase. P[hswa] carries white-apricot (wa) sequences, including a complete copia element, under the control of an hsp70 promoter, and resembles the original wa allele in eye color phenotype. In the presence o...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Kurkulos M,Weinberg JM,Roy D,Mount SM

    更新日期:1994-03-01 00:00:00

  • Estimating the strength of selective sweeps from deep population diversity data.

    abstract::Selective sweeps are typically associated with a local reduction of genetic diversity around the adaptive site. However, selective sweeps can also quickly carry neutral mutations to observable population frequencies if they arise early in a sweep and hitchhike with the adaptive allele. We show that the interplay betwe...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.112.138461

    authors: Messer PW,Neher RA

    更新日期:2012-06-01 00:00:00

  • Gene conversion within regulatory sequences generates maize r alleles with altered gene expression.

    abstract::The maize r locus encodes a transcription factor that regulates the developmental expression of the plant pigment anthocyanin. In an unusual example of gene regulatory diversity, the R-sc (Sc, strong seed color) and the R-p (P, plant color) alleles of r have nonoverlapping tissue specificity and nonhomologous 5' flank...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Li Y,Bernot JP,Illingworth C,Lison W,Bernot KM,Eggleston WB,Fogle KJ,DiPaola JE,Kermicle J,Alleman M

    更新日期:2001-12-01 00:00:00

  • Involvement of the yeast DNA polymerase delta in DNA repair in vivo.

    abstract::The POL3 encoded catalytic subunit of DNA polymerase delta possesses a highly conserved C-terminal cysteine-rich domain in Saccharomyces cerevisiae. Mutations in some of its cysteine codons display a lethal phenotype, which demonstrates an essential function of this domain. The thermosensitive mutant pol3-13, in which...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Giot L,Chanet R,Simon M,Facca C,Faye G

    更新日期:1997-08-01 00:00:00

  • Assessing probability of ancestry using simple sequence repeat profiles: applications to maize inbred lines and soybean varieties.

    abstract::Determining parentage is a fundamental problem in biology and in applications such as identifying pedigrees. Difficulties inferring parentage derive from extensive inbreeding within the population, whether natural or planned; using an insufficient number of hypervariable loci; and from allele mismatches caused by muta...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Berry DA,Seltzer JD,Xie C,Wright DL,Jones ES,Sebastian S,Smith JS

    更新日期:2003-09-01 00:00:00

  • RNA-DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast.

    abstract::A subset of cancers rely on telomerase-independent mechanisms to maintain their chromosome ends. The predominant "alternative lengthening of telomeres" pathway appears dependent on homology-directed repair (HDR) to maintain telomeric DNA. However, the molecular changes needed for cells to productively engage in telome...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.119.302606

    authors: Hu Y,Bennett HW,Liu N,Moravec M,Williams JF,Azzalin CM,King MC

    更新日期:2019-10-01 00:00:00

  • A simple formula useful for positional cloning.

    abstract::We derive a formula for the distribution of the length T of the recombination interval containing a target gene and using N gametes in a region where R kilobases correspond to 1 cM. The formula can be used to calculate the number of meiotic events required to narrow a target gene down to a specific interval size and h...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Durrett RT,Chen KY,Tanksley SD

    更新日期:2002-01-01 00:00:00

  • Counteracting Environmental Chemicals with Coenzyme Q10: An Educational Primer for Use with "Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline".

    abstract::Environmental toxicants are chemicals that negatively affect human health. Although there are numerous ways to limit exposure, the ubiquitous nature of certain environmental toxicants makes it impossible to avoid them entirely. Consequently, scientists are continuously working toward developing strategies for combatin...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.120.303577

    authors: Bradford BR,Briand NE,Fassnacht N,Gervasio ED,Nowakowski AM,FitzGibbon TC,Maurina S,Benjamin AV,Kelly M,Checchi PM

    更新日期:2020-12-01 00:00:00

  • Heterozygote Advantage Is a Common Outcome of Adaptation in Saccharomyces cerevisiae.

    abstract::Adaptation in diploids is predicted to proceed via mutations that are at least partially dominant in fitness. Recently, we argued that many adaptive mutations might also be commonly overdominant in fitness. Natural (directional) selection acting on overdominant mutations should drive them into the population but then,...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.115.185165

    authors: Sellis D,Kvitek DJ,Dunn B,Sherlock G,Petrov DA

    更新日期:2016-07-01 00:00:00

  • Best Prediction of the Additive Genomic Variance in Random-Effects Models.

    abstract::The additive genomic variance in linear models with random marker effects can be defined as a random variable that is in accordance with classical quantitative genetics theory. Common approaches to estimate the genomic variance in random-effects linear models based on genomic marker data can be regarded as estimating ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.119.302324

    authors: Schreck N,Piepho HP,Schlather M

    更新日期:2019-10-01 00:00:00

  • Synaptonemal Complex Central Region Proteins Promote Localization of Pro-crossover Factors to Recombination Events During Caenorhabditis elegans Meiosis.

    abstract::Crossovers (COs) between homologous chromosomes are critical for meiotic chromosome segregation and form in the context of the synaptonemal complex (SC), a meiosis-specific structure that assembles between aligned homologs. During Caenorhabditis elegans meiosis, central region components of the SC (SYP proteins) are e...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.119.302625

    authors: Cahoon CK,Helm JM,Libuda DE

    更新日期:2019-10-01 00:00:00

  • Yeast Mn2+ transporter, Smf1p, is regulated by ubiquitin-dependent vacuolar protein sorting.

    abstract::Conditional cdc1(Ts) mutants of S. cerevisiae arrest with a phenotype similar to that exhibited by Mn(2+)-depleted cells. Sequence similarity between Cdc1p and a class of Mn(2+)-dependent phosphoesterases, as well as the observation that conditional cdc1(Ts) growth can be ameliorated by Mn(2+) supplement, suggests tha...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.167.1.107

    authors: Eguez L,Chung YS,Kuchibhatla A,Paidhungat M,Garrett S

    更新日期:2004-05-01 00:00:00

  • A genomics approach to the detection of positive selection in cattle: adaptive evolution of the T-cell and natural killer cell-surface protein CD2.

    abstract::The detection of adaptive evolution at the molecular level is of interest not only as an insight into the process of evolution but also because of its functional implications for genes of interest. Here, we present the first genomics approach to detecting positive selection operating on the Bos taurus lineage, an impo...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.104.039040

    authors: Lynn DJ,Freeman AR,Murray C,Bradley DG

    更新日期:2005-07-01 00:00:00

  • Intrachromosomal recombination between well-separated, homologous sequences in mammalian cells.

    abstract::In the present study, we investigated intrachromosomal homologous recombination in a murine hybridoma in which the recipient for recombination, the haploid, endogenous chromosomal immunoglobulin mu-gene bearing a mutation in the constant (Cmu) region, was separated from the integrated single copy wild-type donor Cmu r...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Baker MD,Read LR,Ng P,Beatty BG

    更新日期:1999-06-01 00:00:00

  • A comparison of survival and repair of UV-induced DNA damage in cultured insect versus mammalian cells.

    abstract::Survival and unscheduled DNA synthesis (UDS) were measured in a cultured insect cell line, TN-368, and a cultured mammalian cell line, V-79-4, following exposure to several fluences of ultraviolet light. TN-368 cells were approximately seven times more resistant to the lethal effects of UV than V-79 cells, as determin...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Koval TM,Hart RW,Myser WC,Hink WF

    更新日期:1977-11-01 00:00:00

  • A heritable structural alteration of the yeast mitochondrion.

    abstract::Prions have revived interest in hereditary change that is due to change in cellular structure. How pervasive is structural inheritance and what are its mechanisms? Described here is the initial characterization of [Leu(P)], a heritable structural change of the mitochondrion of Saccharomyces cerevisiae that often but n...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Lockshon D

    更新日期:2002-08-01 00:00:00

  • Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity.

    abstract::A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC class I region (coding units or full contigs) in several human and nonhuman primate haplotypes allowed an analysis of single nucleotide variations (SNV) across this entire segment. This diversity was not evenly distributed. It was r...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.106.057034

    authors: Shiina T,Ota M,Shimizu S,Katsuyama Y,Hashimoto N,Takasu M,Anzai T,Kulski JK,Kikkawa E,Naruse T,Kimura N,Yanagiya K,Watanabe A,Hosomichi K,Kohara S,Iwamoto C,Umehara Y,Meyer A,Wanner V,Sano K,Macquin C,Ikeo K,T

    更新日期:2006-07-01 00:00:00

  • Possible derivation of the laboratory mouse genome from multiple wild Mus species.

    abstract::Laboratory strains of mice are thought to be derived from wild populations of Mus domesticus. Many instances of non-domesticus genetic information fixed in these strains have been described, however, and the amount of strain-to-strain genetic variation exceeds that found in wild domesticus populations. In order to est...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Blank RD,Campbell GR,D'Eustachio P

    更新日期:1986-12-01 00:00:00

  • A Bayesian multilocus association method: allowing for higher-order interaction in association studies.

    abstract::For most common diseases with heritable components, not a single or a few single-nucleotide polymorphisms (SNPs) explain most of the variance for these disorders. Instead, much of the variance may be caused by interactions (epistasis) among multiple SNPs or interactions with environmental conditions. We present a new ...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.107.071696

    authors: Albrechtsen A,Castella S,Andersen G,Hansen T,Pedersen O,Nielsen R

    更新日期:2007-06-01 00:00:00

  • Combining data from multiple inbred line crosses improves the power and resolution of quantitative trait loci mapping.

    abstract::Rodent inbred line crosses are widely used to map genetic loci associated with complex traits. This approach has proven to be powerful for detecting quantitative trait loci (QTL); however, the resolution of QTL locations, typically approximately 20 cM, means that hundreds of genes are implicated as potential candidate...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:10.1534/genetics.104.033993

    authors: Li R,Lyons MA,Wittenburg H,Paigen B,Churchill GA

    更新日期:2005-03-01 00:00:00

  • Age-dependent sexually asymmetric selection: the use of intrinsic values.

    abstract::To study the evolutionary role played by differential male and female fertility (sexual asymmetry) both between individuals and over the life span within single individuals, the terms "intrinsic male fertility" and "intrinsic female fertility" are introduced. With the help of these terms, the concept of sexual asymmet...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Gregorius HR

    更新日期:1991-11-01 00:00:00

  • Characterization of X-linked recessive lethal mutations affecting embryonic morphogenesis in Drosophila melanogaster.

    abstract::This study attempted to assay the zygotic contribution of X chromosome genes to the genetic control of embryonic morphogenesis in Drosophila melanogaster. A systematic screen for X-linked genes which affect the morphology of the embryo was undertaken, employing the phenotype of whole mount embryos as the major screeni...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Eberl DF,Hilliker AJ

    更新日期:1988-01-01 00:00:00

  • The role of Gcr1p in the transcriptional activation of glycolytic genes in yeast Saccharomyces cerevisiae.

    abstract::To study the interdependence of Gcr1p and Rap1p, we prepared a series of synthetic regulatory sequences that contained various numbers and combinations of CT-boxes (Gcr1p-binding sites) and RPG-boxes (Rap1p-binding sites). The ability of the synthetic oligonucleotides to function as regulatory sequences was tested usi...

    journal_title:Genetics

    pub_type: 杂志文章

    doi:

    authors: Uemura H,Koshio M,Inoue Y,Lopez MC,Baker HV

    更新日期:1997-10-01 00:00:00