A complex genetic architecture in zebrafish relatives Danio quagga and D. kyathit underlies development of stripes and spots

Vertebrate pigmentation is a fundamentally important, multifaceted phenotype. Zebrafish, Danio rerio, has been a valuable model for understanding genetics and development of pigment pattern formation due to its genetic and experimental tractability, advantages that are shared across several Danio species having a striking array of pigment patterns. Here, we use the sister species D. quagga and D. kyathit, with stripes and spots, respectively, to understand how natural genetic variation impacts phenotypes at cellular and organismal levels. We first show that D. quagga and D. kyathit phenotypes resemble those of wild-type D. rerio and several single locus mutants of D. rerio, respectively, in a morphospace defined by pattern variation along dorsoventral and anteroposterior axes. We then identify differences in patterning at the cellular level between D. quagga and D. kyathit by repeated daily imaging during pattern development and quantitative comparisons of adult phenotypes, revealing that patterns are similar initially but diverge ontogenetically. To assess the genetic architecture of these differences, we employ reduced-representation sequencing of second-generation hybrids. Despite the similarity of D. quagga to D. rerio, and D. kyathit to some D. rerio mutants, our analyses reveal a complex genetic basis for differences between D. quagga and D. kyathit, with several quantitative trait loci contributing to variation in overall pattern and cellular phenotypes, epistatic interactions between loci, and abundant segregating variation within species. Our findings provide a window into the evolutionary genetics of pattern-forming mechanisms in Danio and highlight the complexity of differences that can arise even between sister species. Further studies of natural genetic diversity underlying pattern variation in D. quagga and D. kyathit should provide insights complementary to those from zebrafish mutant phenotypes and more distant species comparisons.

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A complex genetic architecture in zebrafish relatives Danio quagga and D. kyathit underlies development of stripes and spots

10.1101/2021.01.21.427615 ◽

2021 ◽

Author(s):

Braedan M. McCluskey ◽

Susumu Uji ◽

Joseph L. Mancusi ◽

John H. Postlethwait ◽

David M. Parichy

Keyword(s):

Genetic Architecture ◽

Genetic Basis ◽

Evolutionary Genetics ◽

Sister Species ◽

Pigment Cells ◽

Induced Mutations ◽

Pigment Pattern ◽

Wide Range ◽

Pattern Development ◽

Pigment Patterns

AbstractVertebrate pigmentation is a fundamentally important, multifaceted phenotype. Zebrafish, Danio rerio, has been a valuable model for understanding genetics and development of pigment pattern formation due to its genetic and experimental tractability, advantages that are shared across several Danio species having a striking array of pigment patterns. Here, we use the sister species D. quagga and D. kyathit, with stripes and spots, respectively, to understand how natural genetic variation impacts phenotypes at cellular and organismal levels. We first show that D. quagga and D. kyathit phenotypes resemble those of wild-type D. rerio and several single locus mutants of D. rerio, respectively, in a morphospace defined by pattern variation along dorsoventral and anteroposterior axes. We then identify differences in patterning at the cellular level between D. quagga and D. kyathit by repeated daily imaging during pattern development and quantitative comparisons of adult phenotypes, revealing that patterns are similar initially but diverge ontogenetically. To assess the genetic architecture of these differences, we employ reduced-representation sequencing of second-generation hybrids. Despite the similarity of D. quagga to D. rerio, and D. kyathit to some D. rerio mutants, our analyses reveal a complex genetic basis for differences between D. quagga and D. kyathit, with several quantitative trait loci contributing to variation in overall pattern and cellular phenotypes, epistatic interactions between loci, and abundant segregating variation within species. Our findings provide a window into the evolutionary genetics of pattern-forming mechanisms in Danio and highlight the complexity of differences that can arise even between sister species. Further studies of natural genetic diversity underlying pattern variation in D. quagga and D. kyathit should provide insights complementary to those from zebrafish mutant phenotypes and more distant species comparisons.Author SummaryPigment patterns of fishes are diverse and function in a wide range of behaviors. Common pattern themes include stripes and spots, exemplified by the closely related minnows Danio quagga and D. kyathit, respectively. We show that these patterns arise late in development owing to alterations in the development and arrangements of pigment cells. In the closely related model organism zebrafish (D. rerio) single genes can switch the pattern from stripes to spots. Yet, we show that pattern differences between D. quagga and D. kyathit have a more complex genetic basis, depending on multiple genes and interactions between these genes. Our findings illustrate the importance of characterizing naturally occuring genetic variants, in addition to laboratory induced mutations, for a more complete understanding of pigment pattern development and evolution.

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Genetic architecture of quantitative flower and leaf traits in a pair of sympatric sister species of Primulina

Heredity ◽

10.1038/s41437-018-0170-2 ◽

2018 ◽

Vol 122 (6) ◽

pp. 864-876 ◽

Cited By ~ 4

Author(s):

Chen Feng ◽

Chao Feng ◽

Lihua Yang ◽

Ming Kang ◽

Mark D. Rausher

Keyword(s):

Genetic Architecture ◽

Leaf Traits ◽

Sister Species

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Mechanical Forces and Their Effect on the Ribosome and Protein Translation Machinery

Cells ◽

10.3390/cells9030650 ◽

2020 ◽

Vol 9 (3) ◽

pp. 650 ◽

Cited By ~ 2

Author(s):

Lisa J. Simpson ◽

Ellie Tzima ◽

John S. Reader

Keyword(s):

Messenger Rna ◽

Protein Translation ◽

Cellular Level ◽

Mechanical Forces ◽

Active Protein ◽

Translation Machinery ◽

Translational Machinery ◽

Naturally Occurring ◽

Bacterial Ribosome ◽

Cellular Phenotypes

Mechanical forces acting on biological systems, at both the macroscopic and microscopic levels, play an important part in shaping cellular phenotypes. There is a growing realization that biomolecules that respond to force directly applied to them, or via mechano-sensitive signalling pathways, can produce profound changes to not only transcriptional pathways, but also in protein translation. Forces naturally occurring at the molecular level can impact the rate at which the bacterial ribosome translates messenger RNA (mRNA) transcripts and influence processes such as co-translational folding of a nascent protein as it exits the ribosome. In eukaryotes, force can also be transduced at the cellular level by the cytoskeleton, the cell’s internal filamentous network. The cytoskeleton closely associates with components of the translational machinery such as ribosomes and elongation factors and, as such, is a crucial determinant of localized protein translation. In this review we will give (1) a brief overview of protein translation in bacteria and eukaryotes and then discuss (2) how mechanical forces are directly involved with ribosomes during active protein synthesis and (3) how eukaryotic ribosomes and other protein translation machinery intimately associates with the mechanosensitive cytoskeleton network.

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Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain

Neuron ◽

10.1016/j.neuron.2017.01.033 ◽

2017 ◽

Vol 93 (5) ◽

pp. 1094-1109.e7 ◽

Cited By ~ 20

Author(s):

Wei-Chao Huang ◽

Elliott Ferris ◽

Tong Cheng ◽

Cornelia Stacher Hörndli ◽

Kelly Gleason ◽

...

Keyword(s):

Genetic Architecture ◽

Cellular Level ◽

Mammalian Brain ◽

Specific Expression ◽

Allele Specific Expression ◽

Allele Specific

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The Genetic Architecture of Human Infectious Diseases and Pathogen-Induced Cellular Phenotypes

SSRN Electronic Journal ◽

10.2139/ssrn.3707276 ◽

2020 ◽

Author(s):

Andrew Hale ◽

Dan Zhou ◽

Rebecca L. Sale ◽

Lisa Bastarache ◽

Liuyang Wang ◽

...

Keyword(s):

Infectious Diseases ◽

Genetic Architecture ◽

Cellular Phenotypes

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Geography of speciation affects rate of trait divergence in haemulid fishes

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2018.2852 ◽

2019 ◽

Vol 286 (1896) ◽

pp. 20182852 ◽

Cited By ~ 1

Author(s):

José J. Tavera ◽

Peter C. Wainwright

Keyword(s):

Divergence Time ◽

Marine Species ◽

Sister Species ◽

Colour Pattern ◽

Phenotypic Traits ◽

Trait Divergence ◽

Species Pairs ◽

Species Comparisons ◽

Elevated Rate ◽

Patterns And Processes

Speciation and the interactions between recently diverged species are thought to be major causes of ecological and morphological divergence in evolutionary radiations. Here, we explore the extent to which geographical overlap and time since speciation may promote divergence in marine species, which represent a small fraction of currently published studies about the patterns and processes of speciation. A time-calibrated molecular phylogeny of New World haemulid fishes, a major radiation of reef and shore fishes in the tropical West Atlantic and East Pacific, reveals 21 sister species pairs, of which eight are fully sympatric and 13 are allopatric. Sister species comparisons show a non-significant relation between most of the phenotypic traits and time since divergence in allopatric taxa. Additionally, we find no difference between sympatric and allopatric pairs in the rate of divergence in colour pattern, overall body shape, or functional morphological traits associated with locomotion or feeding. However, sympatric pairs show a significant decrease in the rate of divergence in all of these traits with increasing time since their divergence, suggesting an elevated rate of divergence at the time of speciation, the effect of which attenuates as divergence time increases. Our results are consistent with an important role for geographical overlap driving phenotypic divergence early in the speciation process, but the lack of difference in rates between sympatric and allopatric pairs indicates that the interactions between closely related species are not dominant drivers of this divergence.

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A FUNCTIONAL EPIGENETIC CLOCK FOR RATS

Innovation in Aging ◽

10.1093/geroni/igz038.128 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S33-S33

Author(s):

Morgan E Levine ◽

Ross McDevitt ◽

Luigi Ferrucci ◽

Rafael deCabo

Keyword(s):

Open Field ◽

Frailty Index ◽

Functional Enrichment ◽

Longitudinal Change ◽

Phenotypic Traits ◽

Epigenetic Clock ◽

Reduced Representation ◽

Reduced Representation Bisulfite Sequencing ◽

Species Comparisons ◽

Sample Age

Abstract Evidence from humans suggests that incorporation of phenotypic aging measures in the development of epigenetic clocks leads to more functionally relevant biomarkers. As a result, the aim of this study was to utilize a deeply phenotyped rat cohort—that included data from rotarod, open field, frailty index, and FACS—to generate a novel epigenetic clock. DNA methylation was assessed via reduced representation bisulfite sequencing (RRBS) for n=142 male Fischer rats from NIA aging colony, ranging in age from 1 to 27 months. Phenotypic traits were combined to generate an multi-system aging measure that was then used to train the epigenetic clock. Using an independent validation sample, age-adjusted epigenetic clock measures were associated with numerous traits, including: open field time resting (p=0.005), open field time climbing (p=0.001), body weight (p=0.02), and rotarod max (p=0.04). In moving forward, it will be important to examine cross-species comparisons, longitudinal change, and functional enrichment.

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The utility of genomic prediction models in evolutionary genetics

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2021.0693 ◽

2021 ◽

Vol 288 (1956) ◽

pp. 20210693

Author(s):

Suzanne E. McGaugh ◽

Aaron J. Lorenz ◽

Lex E. Flagel

Keyword(s):

Best Practices ◽

Genomic Prediction ◽

Complex Traits ◽

Genetic Architecture ◽

Prediction Models ◽

Evolutionary Genetics ◽

Breeding Value ◽

Evolutionary Genomics ◽

Genome Wide ◽

Genetic Value

Variation in complex traits is the result of contributions from many loci of small effect. Based on this principle, genomic prediction methods are used to make predictions of breeding value for an individual using genome-wide molecular markers. In breeding, genomic prediction models have been used in plant and animal breeding for almost two decades to increase rates of genetic improvement and reduce the length of artificial selection experiments. However, evolutionary genomics studies have been slow to incorporate this technique to select individuals for breeding in a conservation context or to learn more about the genetic architecture of traits, the genetic value of missing individuals or microevolution of breeding values. Here, we outline the utility of genomic prediction and provide an overview of the methodology. We highlight opportunities to apply genomic prediction in evolutionary genetics of wild populations and the best practices when using these methods on field-collected phenotypes.

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Punctuated loci on chromosome IV determine natural variation in Orsay virus susceptibility of Caenorhabditis elegans strains Bristol N2 and Hawaiian CB4856

10.1101/2020.10.30.361683 ◽

2020 ◽

Author(s):

Mark G. Sterken ◽

Lisa van Sluijs ◽

Yiru A. Wang ◽

Wannisa Ritmahan ◽

Mitra L. Gultom ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Genetic Architecture ◽

Recombinant Inbred Lines ◽

Natural Genetic Variation ◽

C Elegans ◽

Viral Susceptibility ◽

The Difference ◽

Multiple Strains ◽

Orsay Virus ◽

Insight Into

AbstractHost-pathogen interactions play a major role in evolutionary selection and shape natural genetic variation. The genetically distinct Caenorhabditis elegans strains, Bristol N2 and Hawaiian CB4856, are differentially susceptible to the Orsay virus (OrV). Here we report the dissection of the genetic architecture of susceptibility to OrV infection. We compare OrV infection in the relatively resistant wild-type CB4856 strain to the more susceptible canonical N2 strain. To gain insight into the genetic architecture of viral susceptibility, 52 fully sequenced recombinant inbred lines (CB4856 x N2 RILs) were exposed to OrV. This led to the identification of two loci on chromosome IV associated with OrV resistance. To verify the two loci and gain additional insight into the genetic architecture controlling virus infection, introgression lines (ILs) that together cover chromosome IV, were exposed to OrV. Of the 27 ILs used, 17 had an CB4856 introgression in an N2 background and 10 had an N2 introgression in a CB4856 background. Infection of the ILs confirmed and fine-mapped the locus underlying variation in OrV susceptibility and we found that a single nucleotide polymorphism in cul-6 contributes to the difference in OrV susceptibility between N2 and CB4856. An allele swap experiment showed the strain CB4856 became more susceptible by having an N2 cul-6 allele, although having the CB4856 cul-6 allele did not increase resistance in N2. Additionally, we found that multiple strains with non-overlapping introgressions showed a distinct infection phenotype from the parental strain, indicating that there are punctuated locations on chromosome IV determining OrV susceptibility. Thus, our findings reveal the genetic complexity of OrV susceptibility in C. elegans and suggest that viral susceptibility is governed by multiple genes.

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Bayesian analysis of GWAS summary data reveals differential signatures of natural selection across human complex traits and functional genomic categories

10.1101/752527 ◽

2019 ◽

Cited By ~ 6

Author(s):

Jian Zeng ◽

Angli Xue ◽

Longda Jiang ◽

Luke R Lloyd-Jones ◽

Yang Wu ◽

...

Keyword(s):

Natural Selection ◽

Complex Traits ◽

Genetic Architecture ◽

Evolutionary Genetics ◽

Functional Genomic ◽

Individual Level ◽

Level Data ◽

Genomic Regions ◽

Evolutionary Simulations ◽

Transcriptional Start Sites

AbstractUnderstanding how natural selection has shaped the genetic architecture of complex traits and diseases is of importance in medical and evolutionary genetics. Bayesian methods have been developed using individual-level data to estimate multiple features of genetic architecture, including signatures of natural selection. Here, we present an enhanced method (SBayesS) that only requires GWAS summary statistics and incorporates functional genomic annotations. We analysed GWAS data with large sample sizes for 155 complex traits and detected pervasive signatures of negative selection with diverse estimates of SNP-based heritability and polygenicity. Projecting these estimates onto a map of genetic architecture obtained from evolutionary simulations revealed relatively strong natural selection on genetic variants associated with cardiorespiratory and cognitive traits and relatively small number of mutational targets for diseases. Averaging across traits, the joint distribution of SNP effect size and MAF varied across functional genomic regions (likely to be a consequence of natural selection), with enrichment in both the number of associated variants and the magnitude of effect sizes in regions such as transcriptional start sites, coding regions and 5’- and 3’-UTRs.

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