scholarly journals A novel enhancer of Agouti contributes to parallel evolution of cryptically colored beach mice

2021 ◽  
Author(s):  
T Brock Wooldridge ◽  
Andreas F Kautt ◽  
Jean-Marc Lassance ◽  
Sade S McFadden ◽  
Vera S Domingues ◽  
...  
Keyword(s):  
Evolutionary History ◽  
Coat Color ◽  
Atlantic Coast ◽  
Parallel Evolution ◽  
Regulatory Region ◽  
Color Variation ◽  
Coding Region ◽  
Peromyscus Polionotus ◽  
Southeastern Us ◽  
Gene Assay

Identifying the genetic basis of repeatedly evolved traits provides a way to reconstruct their evolutionary history and ultimately investigate the predictability of evolution. Here, we focus on the oldfield mouse (Peromyscus polionotus), which occurs in the southeastern United States, where it exhibits considerable coat-color variation. Dorsal coats range from dark brown in mice inhabiting mainland habitat to near white on the white-sand beaches of the southeastern US, where light pelage has evolved independently on Florida's Gulf and Atlantic coasts as an adaptation to visually hunting predators. To facilitate genomic analyses in this species, we first generated a high-quality, chromosome-level genome assembly of P. polionotus subgriseus. Next, in a uniquely variable mainland population that occurs near beach habitat (P. p. albifrons), we scored 23 pigment traits and performed targeted resequencing in 168 mice. We find that variation in pigmentation is strongly associated with a ~2 kb region approximately 5 kb upstream of the Agouti-signaling protein (ASIP) coding region. Using a reporter-gene assay, we demonstrate that this regulatory region contains an enhancer that drives expression in the dermis of mouse embryos during the establishment of pigment prepatterns. Moreover, extended tracts of homozygosity in this region of Agouti indicate that the light allele has experienced recent and strong positive selection. Notably, this same light allele appears fixed in both Gulf and Atlantic coast beach mice, despite these populations being separated by >1,000km. Given the evolutionary history of this species, our results suggest that this newly identified Agouti enhancer allele has been maintained in mainland populations as standing genetic variation and from there has spread to, and been selected in, two independent beach mouse lineages, thereby facilitating their rapid and parallel evolution.

scholarly journals A potential regulatory region near the EDN3 gene may control both harness racing performance and coat color variation in horses

2018 ◽  
Vol 6 (10) ◽  
pp. e13700 ◽  
Author(s):  
Kim Jäderkvist Fegraeus ◽  
Brandon D. Velie ◽  
Jeanette Axelsson ◽  
Rachel Ang ◽  
Natasha A. Hamilton ◽  
...  
Keyword(s):  
Coat Color ◽  
Regulatory Region ◽  
Color Variation ◽  
Racing Performance ◽  
Harness Racing

scholarly journals Detecting subtle variation in two cryptic primate families (tarsiidae and lorisidae) through morphology and genetics

2018 ◽  
Author(s):  
◽  
Rachel Anne Munds
Keyword(s):  
Candidate Gene ◽  
Cryptic Species ◽  
Evolutionary History ◽  
Coat Color ◽  
Color Variation ◽  
Cranial Variation ◽  
The Family ◽  
History Of ◽  
Slow Moving ◽  
African Genus

Cryptic species look morphologically similar but in fact are several different species lumped together. This is problematic as it hinders conservation efforts and makes it challenging to infer the evolutionary history of an organism. This dissertation research aims to improve our understanding of the evolution and variation of cryptic, nocturnal primates. Over 60% of primates are threatened with extinction, and many nocturnal species are poorly understood. Research aimed at elucidating species will help conserve them. To do so, I examined the multivariate craniodental allometry of the three genera of tarsiers. Tarsiers are small-bodied, nocturnal primates that have evolved to extreme-carnivorous niche. In order to see better at night their eyes have increased dramatically in size. Such evolution has led to minimal cranial variation among the three groups, despite millions of years of separation. Yet, two distinct groups were found through allometric analyses. Genetics is another tool that can discern the evolution and variation of cryptic species. The slow moving lorises of Asia and Africa appear morphologically similar, making it a challenge to determine their evolutionary history or variation. By using a multi-gene approach, I was able to determine the family is monophyletic with four distinct genera. Furthermore, analyses of a candidate gene that impacts coat color variation, found that the darker colored African genus has more mutations along its branch that result in amino acid changes than the vibrantly colored lorises in Asia. Such a result suggests that a transition to or a maintenance of a darker phenotype is conserved or that other genes besides this one candidate gene influence coat variation. Overall, I was able to find that through a variety of methods, it is possible to detect variation and the evolutionary history of cryptic species.

scholarly journals Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus.

Genetics ◽  
1995 ◽  
Vol 140 (1) ◽  
pp. 255-265 ◽  
Author(s):  
C M Hustad ◽  
W L Perry ◽  
L D Siracusa ◽  
C Rasberry ◽  
L Cobb ◽  
...  
Keyword(s):  
Coat Color ◽  
Molecular Genetic ◽  
Regulatory Region ◽  
Chromosome 2 ◽  
Coding Region ◽  
Range Restriction ◽  
Agouti Locus ◽  
Regulatory Mutations ◽  
Immunological Disorder ◽  
Mouse Chromosome 2

Abstract The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (amJ, au, ada, a16H, a18H, ae) were examined at both the RNA and DNA level. Two of the alleles, a16H and ae, result from mutations in the agouti coding region. Four alleles (amJ, au, a18H, and ada) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a18H, also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a18H DNA are consistent with the hypothesis that a18H results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder.

scholarly journals Introgression drives repeated evolution of winter coat color polymorphism in hares

2019 ◽  
Vol 116 (48) ◽  
pp. 24150-24156 ◽  
Author(s):  
Iwona Giska ◽  
Liliana Farelo ◽  
João Pimenta ◽  
Fernando A. Seixas ◽  
Mafalda S. Ferreira ◽  
...  
Keyword(s):  
Coat Color ◽  
Color Change ◽  
Regulatory Region ◽  
Bird Species ◽  
Color Polymorphism ◽  
Genomic Region ◽  
Population History ◽  
Color Variation ◽  
Source Population ◽  
Whole Genome

Changing from summer-brown to winter-white pelage or plumage is a crucial adaptation to seasonal snow in more than 20 mammal and bird species. Many of these species maintain nonwhite winter morphs, locally adapted to less snowy conditions, which may have evolved independently. Mountain hares (Lepus timidus) from Fennoscandia were introduced into the Faroe Islands in 1855. While they were initially winter-white, within ∼65 y all Faroese hares became winter-gray, a morph that occurs in the source population at low frequency. The documented population history makes this a valuable model for understanding the genetic basis and evolution of the seasonal trait polymorphism. Through whole-genome scans of differentiation and single-nucleotide polymorphism (SNP) genotyping, we associated winter coat color polymorphism to the genomic region of the pigmentation gene Agouti, previously linked to introgression-driven winter coat color variation in the snowshoe hare (Lepus americanus). Lower Agouti expression in the skin of winter-gray individuals during the autumn molt suggests that regulatory changes may underlie the color polymorphism. Variation in the associated genomic region shows signatures of a selective sweep in the Faroese population, suggesting that positive selection drove the fixation of the variant after the introduction. Whole-genome analyses of several hare species revealed that the winter-gray variant originated through introgression from a noncolor changing species, in keeping with the history of ancient hybridization between the species. Our findings show the recurrent role of introgression in generating winter coat color variation by repeatedly recruiting the regulatory region of Agouti to modulate seasonal coat color change.

scholarly journals Unexpectedly High Allelic Diversity at the KIT Locus Causing Dominant White Color in the Domestic Pig

Genetics ◽  
2002 ◽  
Vol 160 (1) ◽  
pp. 305-311
Author(s):  
G Pielberg ◽  
C Olsson ◽  
A-C Syvänen ◽  
L Andersson
Keyword(s):  
Coat Color ◽  
Allelic Diversity ◽  
Growth Factor Receptor ◽  
Small Sample ◽  
Color Variation ◽  
Large White ◽  
High Genetic Diversity ◽  
High Allelic Diversity ◽  
Stem Cell Growth Factor ◽  
New Alleles

Abstract Mutations in KIT encoding the mast/stem cell growth factor receptor (MGF) are responsible for coat color variation in domestic pigs. The dominant white phenotype is caused by two mutations, a gene duplication and a splice mutation in one of the copies leading to skipping of exon 17. Here we applied minisequencing and pyrosequencing for quantitative analysis of the number of copies with the splice form. An unexpectedly high genetic diversity was revealed in white pigs. We found four different KIT alleles in a small sample of eight Large White females used as founder animals in a wild boar intercross. A similar number of KIT alleles was found in commercial populations of white Landrace and Large White pigs. We provide evidence for at least two new KIT alleles in pigs, both with a triplication of the gene. The results imply that KIT alleles with the duplication are genetically unstable and new alleles are most likely generated by unequal crossing over. This study provides an improved method for genotyping the complicated Dominant white/KIT locus in pigs. The results also suggest that some alleles may be associated with negative pleiotropic effects on other traits.

Inherent hepatocytic heterogeneity determines expression and retention of edited F9 alleles post-AAV/CRISPR infusion

2021 ◽  
Vol 118 (42) ◽  
pp. e2110887118
Author(s):  
Qiang Wang ◽  
Lin Zhang ◽  
Guo-Wei Zhang ◽  
Jian-Hua Mao ◽  
Xiao-Dong Xi ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Gene Editing ◽  
Regulatory Region ◽  
Factor Ix ◽  
Host Cells ◽  
Clotting Factor ◽  
Dependent Manner ◽  
Coding Region ◽  
Therapeutic Benefits

Infusing CRISPR/donor-loaded adeno-associated viral vectors (AAV/CRISPR) could enable in vivo hepatic gene editing to remedy hemophilia B (HB) with inherited deficiency of clotting factor IX (FIX). Yet, current regimens focus on correcting HB with simple mutations in the coding region of the F9, overlooking those carrying complicated mutations involving the regulatory region. Moreover, a possible adverse effect of treatment-related inflammation remains unaddressed. Here we report that a single DNA cutting-mediated long-range replacement restored the FIX-encoding function of a mutant F9 (mF9) carrying both regulatory and coding defects in a severe mouse HB model, wherein incorporation of a synthetic Alb enhancer/promoter-mimic (P2) ensured FIX elevation to clinically meaningful levels. Through single-cell RNA sequencing (scRNA-seq) of liver tissues, we revealed that a subclinical hepatic inflammation post-AAV/CRISPR administration regulated the vulnerability of the edited mF9-harboring host cells to cytotoxic T lymphocytes (CTLs) and the P2 activity in a hepatocytic subset–dependent manner via modulating specific sets of liver-enriched transcription factors (LETFs). Collectively, our study establishes an AAV/CRISPR-mediated gene-editing protocol applicable to complicated monogenetic disorders, underscoring the potentiality of improving therapeutic benefits through managing inflammation.

scholarly journals Signal peptide specificity in posttranslational processing of the plant protein phaseolin in Saccharomyces cerevisiae.

1987 ◽  
Vol 7 (1) ◽  
pp. 121-128 ◽  
Author(s):  
J H Cramer ◽  
K Lea ◽  
M D Schaber ◽  
R A Kramer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Acid Phosphatase ◽  
Signal Peptide ◽  
Regulatory Region ◽  
Cellular Protein ◽  
Proteolytic Processing ◽  
Coding Region ◽  
Molecular Weights ◽  
Amino Terminal ◽  
Acid Phosphatase Gene

We linked the cDNA coding region for the bean storage protein phaseolin to the promoter and regulatory region of the Saccharomyces cerevisiae repressible acid phosphatase gene (PHO5) in multicopy expression plasmids. Yeast transformants containing these plasmids expressed phaseolin at levels up to 3% of the total soluble cellular protein. Phaseolin polypeptides in S. cerevisiae were glycosylated, and their molecular weights suggested that the signal peptide had been processed. We also constructed a series of plasmids in which the phaseolin signal-peptide-coding region was either removed or replaced with increasing amounts of the amino-terminal coding region for acid phosphatase. Phaseolin polypeptides with no signal peptide were not posttranslationally modified in S. cerevisiae. Partial or complete substitution of the phaseolin signal peptide with that from acid phosphatase dramatically inhibited both signal peptide processing and glycosylation, suggesting that some specific feature of the phaseolin signal amino acid sequence was required for these modifications to occur. Larger hybrid proteins that included approximately one-half of the acid phosphatase sequence linked to the amino terminus of the mature phaseolin polypeptide did undergo proteolytic processing and glycosylation. However, these polypeptides were cleaved at several sites that are not normally used in the unaltered acid phosphatase protein.

The gene for the heat-shock protein 70 of Euplotes focardii, an Antarctic psychrophilic ciliate

2004 ◽  
Vol 16 (1) ◽  
pp. 23-28 ◽  
Author(s):  
ANTONIETTA LA TERZA ◽  
CRISTINA MICELI ◽  
PIERANGELO LUPORINI
Keyword(s):  
Thermal Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Regulatory Region ◽  
Regulatory Elements ◽  
Specific Response ◽  
Hsp70 Gene ◽  
Sequence Motifs ◽  
Coding Region

In the Antarctic ciliate, Euplotes focardii, the heat-shock protein 70 (Hsp70) gene does not show any appreciable activation by a thermal stress. Yet, it is activated to appreciable transcriptional levels by oxidative and chemical stresses, thus implying that it evolved a mechanism of selective, stress-specific response. A basic step in investigating this mechanism is the determination of the complete nucleotide sequence of the E. focardii Hsp70 gene. This gene contains a coding region specific for an Hsp70 protein that carries unique amino acid substitutions of potential significance for cold adaptation, and a 5' regulatory region that includes sequence motifs denoting two distinct types of stress-inducible promoters, known as “Heat Shock Elements” (HSE) and “Stress Response Elements” (StRE). From the study of the interactions of these regulatory elements with their specific transactivator factors we expect to shed light on the adaptive modifications that prevent the Hsp70 gene of E. focardii from responding to thermal stress while being responsive to other stresses.

scholarly journals Roles of Transcription Factor Mot3 and Chromatin in Repression of the Hypoxic Gene ANB1 in Yeast

2000 ◽  
Vol 20 (19) ◽  
pp. 7088-7098 ◽  
Author(s):  
Alexander J. Kastaniotis ◽  
Thomas A. Mennella ◽  
Christian Konrad ◽  
Ana M. Rodriguez Torres ◽  
Richard S. Zitomer
Keyword(s):  
Binding Site ◽  
Regulatory Region ◽  
Direct Interaction ◽  
Minor Effect ◽  
Histone H4 ◽  
Coding Region ◽  
Basal Transcriptional Machinery ◽  
In The Wild ◽  
A Minor

ABSTRACT The hypoxic genes of Saccharomyces cerevisiae are repressed by a complex consisting of the aerobically expressed, sequence-specific DNA-binding protein Rox1 and the Tup1-Ssn6 general repressors. The regulatory region of one well-studied hypoxic gene,ANB1, is comprised of two operators, OpA and OpB, each of which has two strong Rox1 binding sites, yet OpA represses transcription almost 10 times more effectively than OpB. We show here that this difference is due to the presence of a Mot3 binding site in OpA. Mutations in this site reduced OpA repression to OpB levels, and the addition of a Mot3 binding site to OpB enhanced repression. Deletion of the mot3 gene also resulted in reduced repression of ANB1. Repression of two other hypoxic genes in which Mot3 sites were associated with Rox1 sites was reduced in the deletion strain, but other hypoxic genes were unaffected. In addition, the mot3Δ mutation caused a partial derepression of the Mig1–Tup1-Ssn6-repressed SUC2 gene, but not the α2–Mcm1–Tup1-Ssn6-repressed STE2 gene. The Mot3 protein was demonstrated to bind to the ANB1 OpA in vitro. Competition experiments indicated that there was no interaction between Rox1 and Mot3, indicating that Mot3 functions either in Tup1-Ssn6 recruitment or directly in repression. A great deal of evidence has accumulated suggesting that the Tup1-Ssn6 complex represses transcription through both nucleosome positioning and a direct interaction with the basal transcriptional machinery. We demonstrate here that under repressed conditions a nucleosome is positioned over the TATA box in the wild-type ANB1promoter. This nucleosome was absent in cells carrying arox1, tup1, or mot3 deletion, all of which cause some degree of derepression. Interestingly, however, this positioned nucleosome was also lost in a cell carrying a deletion of the N-terminal coding region of histone H4, yet ANB1expression remained fully repressed. A similar deletion in the gene for histone H3, which had no effect on repression, had only a minor effect on the positioned nucleosome. These results indicate that the nucleosome phasing on the ANB1 promoter caused by the Rox1–Mot3–Tup1-Ssn6 complex is either completely redundant with a chromatin-independent repression mechanism or, less likely, plays no role in repression at all.

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