People have long been fascinated with birds, which exhibit one of the widest ranges of coloration among vertebrates. Parrots, in particular, have captivated humans by their ability to mimic human speech and spectacular plumage.

Brightly colored feathers are used primarily to attract mates, intimidate competitors, and protect birds from predators. Coloration is both environmentally and genetically mediated, and research into its genetic control can help us better understand its role in adaptation and survival.

Blue and yellow pigmentation combine to create the green hue—which blends well with the tree canopy—most commonly seen in wild parrots. In contrast, yellow alone is a popular color for captive-bred parrots. A study published in the February issue of G3: Genes|Genomes|Genetics investigates the molecular basis of yellow color variations in three species of captive-bred parrots.

Parrots’ yellow coloration has connections to albinism in humans

Researchers at the University of the Negev, led by principal investigator Uri Abdu, report that a mutation in SLC45A2 is responsible for the sex-linked yellow phenotype seen in Psittacula krameri and two other parrot species.

Although most birds employ dietary carotenoid pigments for yellow coloration, parrots use a unique group of pigments called psittacofulvins. The blue color of parrot plumage is partly due to light scattering by nanostructures within the feathers. Data suggested that the presence of melanosomes also plays a role in producing blue coloration. In contrast, the absence of melanosomes allows the solitary expression of yellow coloration.

Breeder data indicates that the yellow parrot phenotype is usually sex-linked. Unlike humans, sex chromosomes in birds are designated as Z and W. The male is the homomorphic sex (ZZ), and the female is heteromorphic (ZW). Pedigree analysis from breeders who supplied birds for the study implied that the sex-linked yellow locus resided on the Z chromosome. Therefore, the researchers hypothesized that a defect in a melanin synthesis gene located on the Z chromosome was primarily responsible for the yellow phenotype.

Using whole-genome sequencing, researchers zeroed in on one Z-chromosome gene with the help of previously annotated budgerigar genome data. They found one protein-terminating nonsense mutation and three nonsynonymous SLC45A2 polymorphisms in yellow parrots that were absent in wild-type parrots. Parrots with this mutation “lose melanin in their entire bodies,” Abdu explains.

In humans, changes in this gene can lead to oculocutaneous albinism type 4 (OCA4), which causes very little pigmentation. One of the mutations found in yellow Psitticula krameri is reported in the human albinism database and is associated with OCA4. Although mutations that can lead to albinism affect many species, this study provides the first evidence of parrot color variation involving SLC45A2.

Better genetic understanding supports breeding and conservation efforts

Shatadru Ghosh Roy, a Ph.D. candidate in Abdu’s lab, explains that this research can save breeders time and produce healthier hatchlings. To maintain the coveted yellow color mutation, breeders traditionally bred siblings, which led to unhealthy hatchlings that often died from lethal mutations. Now that breeders know the genetic basis of yellow coloration, they can breed parrots from distinct bloodlines and avoid the negative effects of inbreeding.

Another takeaway from this work concerns the parrot as a model organism. Abdu considers the parrot an ideal model system for studying the physical and genetic mechanisms underlying avian coloration. After all, parrots have been bred in captivity for decades—indeed, half of all parrots alive live in captivity—and breeders can provide abundant genetic information. Hopefully, more basic biological studies on parrots will add to the knowledge needed to keep parrots alive in the wild. Coloration is part of the parrot puzzle, and additional genetic research into these fascinating birds may uncover strategies to fight the extinction of natural populations. With almost one-third of wild parrot species threatened with extinction, Polly needs all the help she can get.

Analysis of insulin-like signaling in C. elegans reveals extensive positive and negative feedback regulation.

The insulin-like signaling system of nematode worms is comparable to that of more complex organisms; it helps regulate a wide range of the animal’s biology, including metabolism, growth, and development. This system is remarkably flexible, with the ability to maintain a physiological steady-state (homeostasis) while also controlling switches between quite different developmental fates (developmental plasticity). A report published in GENETICS reveals the pervasive involvement of both positive and negative feedback in regulating this master pathway in the model nematode Caenorhabditis elegans.

The C. elegans genome encodes one insulin-like receptor and 40 insulin-like signaling proteins. The activity of insulin-like peptides can, in turn, affect the expression of these peptides themselves, yet exactly how this signaling network is regulated remains ambiguous. Kaplan et al. explored the extent of the feedback mechanisms of insulin-like signaling, along with their dependence on nutrient availability.

The worm insulin-like receptor, DAF-2, signals through antagonizing the activity of the transcription factor DAF-16, the nematode ortholog of mammalian FoxO. Because of these opposing functions, daf-2– and daf-16-mutant nematodes were employed to observe how changes in insulin-like signaling affect the expression of insulin-like genes.

Using these mutants under multiple conditions, such as fed vs. starved larval worms, the authors analyzed the expression of insulin-like genes, along with other genes involved in insulin-like signaling, like those in the PI3K pathway.

The authors found extensive feedback regulations within insulin-like signaling; the expression of nearly all detectable insulin-like genes was affected by altering insulin-like signaling, as were some components of the PI3K pathway. These feedback mechanisms were extensive and complex; for example, the well-studied insulin-like protein DAF-28, an agonist of DAF-2, seems to be repressed by DAF-16—thus, DAF-28 is a positive regulator of its own transcription, since activating DAF-2 represses DAF-16.

Overall, considerable evidence for both negative and positive feedback of insulin-like signaling was found; the authors write that this is likely to allow for rapid response to stimuli—like food availability—while still maintaining homeostasis. Further studies will be needed to delve into the precise molecular mechanisms of such feedback systems and to explore similar regulation in other organisms.

CITATION:

Pervasive Positive and Negative Feedback Regulation of Insulin-Like Signaling in Caenorhabditis elegans

Rebecca E. W. Kaplan, Colin S. Maxwell, Nicole Kurhanewicz Codd, L. Ryan Baugh

GENETICS  January 2019 211: 349-361; https://doi.org/10.1534/genetics.118.301702

https://www.genetics.org/content/211/1/349

Programmed ribosomal frameshifting has translational costs that may influence codon usage bias.

The genetic code has some redundancy—the same amino acid is often encoded by several codons. However, these codons are not necessarily equal in their effect, as evidenced by the codon usage bias observed in many organisms. The translation efficiency hypothesis posits that some codons are more easily translated than others, and these are the ones more commonly used. Based on this hypothesis, the codon usage bias index of a given mRNA should correlate closely with its translation efficiency—but in a report in G3: Genes|Genomes|Genetics, Garcia et al. explain why this might not always be the case.

Programmed ribosomal frameshifting (PRF) occurs when a ribosome stalls at specific sequences—appropriately termed “slippery sites”—which shifts  translation to a new reading frame. The authors were specifically interested in “-1 PRF” cases, where the ribosome moves a single nucleotide backward during translation. This phenomenon is ubiquitous across the tree of life, and it is generally used by eukaryotes as a way to regulate gene expression, but the authors wondered if it could also induce translational costs.

To test this, they used the database PRFdb to examine associations between -1 PRF signals and gene expression in yeast, determining that -1 PRF signals are less common in highly expressed genes. They also found that these signals tend to be present towards the start of open reading frames, which makes sense if the -1 PRF signals are causing translational costs—if the signals occur towards the start of the mRNA, translation is disrupted more quickly, so less energy is wasted. These lines of evidence support the idea that PRF signals do incur translational costs.

The authors then retested the association between codon usage bias and translational efficiency while accounting for the cost of -1 PRF signals. Using a set of mathematical models, they found that incorporating this data generally strengthened support of the translational efficiency hypothesis—that is, more costly transcripts were less often translated, whether the cost was incurred due to codon usage bias or -1 PRF signals. Better understanding these phenomena may help elucidate how translational efficiency is controlled.

CITATION:

Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices

Victor Garcia, Stefan Zoller, Maria Anisimova

G3: Genes, Genomes, Genetics October 2018 8: 3173-3183; https://doi.org/10.1534/g3.118.200185

http://www.g3journal.org/content/8/10/3173

[wysija_form id=”1″]

Offshoot of the modENCODE project provides crucial data and strains for understanding gene regulation.

Following a multidisciplinary effort spanning six institutions, researchers working on the modERN (model organism Encyclopedia of Regulatory Networks) project have released a powerful resource for biologists studying the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. So far, report Kudron, Victorsen, et al., the project has yielded information about the interactions of 262 transcription factors (TFs) with 1.23 million binding sites in flies, along with 219 TFs with 670,000 binding sites in worms—all of which can be found in a searchable database organized by gene and developmental stage.

Along with announcing the availability of this resource, the group shared findings made during its construction. One such observation is that genomic regions with a large number of TF binding sites are often associated with broadly expressed genes, whereas regions with fewer TF binding sites are more often found near genes that are expressed mainly in specific tissues.

The collection includes 403 worm strains and 427 fly strains, each of which has a different TF tagged with green fluorescent protein. Researchers can obtain stocks through existing resources, the Caenorhabditis Genetics Center and the Bloomington Drosophila Stock Center. The strains have a variety of possible uses—for example, determining expression patterns of TF genes of interest.

Choosing flies and worms for the modERN project was a logical choice for multiple reasons, not least of which being that so much is known about these important model organisms. The authors also note that a major advantage of working with flies and worms for this project is that they can be studied as whole, living organisms at all developmental stages, which is not possible with human subjects. And since many fly and worm TFs are homologous to human TFs, it’s likely that research fueled by modERN data will provide a treasure trove of useful leads for biologists studying humans as well.

CITATION:

The ModERN Resource: Genome-Wide Binding Profiles for Hundreds of Drosophila and Caenorhabditis elegans Transcription Factors
Michelle M. Kudron, Alec Victorsen, Louis Gevirtzman, LaDeana W. Hillier, William W. Fisher, Dionne Vafeados, Matt Kirkey, Ann S. Hammonds, Jeffery Gersch, Haneen Ammouri, Martha L. Wall, Jennifer Moran, David Steffen, Matt Szynkarek, Samantha Seabrook-Sturgis, Nader Jameel, Madhura Kadaba, Jaeda Patton, Robert Terrell, Mitch Corson, Timothy J. Durham, Soo Park, Swapna Samanta, Mei Han, Jinrui Xu, Koon-Kiu Yan, Susan E. Celniker, Kevin P. White, Lijia Ma, Mark Gerstein, Valerie Reinke, Robert H. Waterston
Genetics 2018 208: 937-949; https://doi.org/10.1534/genetics.117.300657
http://www.genetics.org/content/208/3/937

Photosensitive alternative splicing of a malt fly circadian clock gene varies between northern and southern populations.

Over the course of a day, most organisms undergo profound changes. Over the course of a season, the changes can be even more dramatic. For example, insects’ responses to the brisk nights and cooler days of fall and winter often involve transformations of both physiology and behavior, including reproduction, activity level, and metabolism. Whether in insects or humans, these daily and seasonal transitions are in part controlled by the internal circadian clock, with the expression of circadian genes responding to rhythmic environmental fluctuations.

Tapanainen et al. wondered how alternative splicing—a common gene regulatory mechanism—of the core circadian gene timeless might be linked to light and temperature in the fly Drosophila montana, a much more cold-tolerant relative of the familiar lab model D. melanogaster. They discovered that in D. montana, timeless splicing is regulated only by the amount of daily light exposure, not by temperature—in contrast to the thermal regulation seen in D. melanogaster. There was also no evidence that northern or southern D. montana had a particular timeless splice variant found in many cold-adapted D. melanogaster populations.

The group also made a peculiar observation: the way timeless splicing was regulated in D. montana differed depending on where the flies originated. For any given number of hours of light per day, if a splice variant was more abundant in flies from northern populations in North America and Europe, it was less abundant in flies from southern populations of the same continents, and vice versa. That the regulation of critical genes can be completely reversed even in two populations of the same species is a reminder of the importance of studying individuals from different populations and regions—perhaps especially in research on something as complex as the circadian clock.

CITATION:
Photosensitive Alternative Splicing of the Circadian Clock Gene timeless Is Population Specific in a Cold-Adapted Fly, Drosophila montana
Riikka Tapanainen, Darren J. Parker, Maaria Kankare
G3: Genes|Genomes|Genetics 2018 8: 1291-1297; https://doi.org/10.1534/g3.118.200050
http://www.g3journal.org/content/8/4/1291

Although foxes look cuddly, these wild animals are equipped with sharp bites—and temperaments to match. Fear not, however, if you’re dying to get close to theses fluffy foxes: a nearly 60-year-old experiment has produced a line of them that are friendly enough to pet.  

The process of creating these tame foxes mirrors the way dogs are thought to have been domesticated from their wild wolf ancestors. These friendly foxes have altered hormone balances, and many of them have dog-like changes in appearance, such as white spotting and curled tails. In a report published in G3: Genes|Genomes|Genetics, Hekman et al. delve into the genetics of these tame foxes, taking a detailed look at their brains.

The tame foxes are the result of a famous experiment started at the Institute of Cytology and Genetics in Siberia, in which the animals were selectively bred for traits like agreeability. For comparison, a line of more aggressive foxes was also bred so that differences between the two groups could illuminate the usually slow processes of domestication.

Levels of the stress hormone cortisol are much lower in the blood of tame foxes than in the aggressive animals. “The question that was really driving me was: What’s different in the brain?” says Jessica Hekman, lead author of the study.

Hekman and her colleagues used RNA sequencing to measure gene expression in the pituitary glands of tame and aggressive foxes. They were interested in the pituitary because it is vital in coordinating the release of many hormones—including cortisol.

The researchers found that genes related to exocytosis were differentially expressed, which suggests the cells could be secreting neurotransmitters and hormones to the blood differently in the two lines. Given the differing levels of blood cortisol observed, this wasn’t all that surprising.

Some other differentially expressed genes were more unexpected, however. “I kept finding a bunch of genes related to pseudopodia, which was a huge surprise,” Hekman recalls. Pseudopodia are cellular protrusions best known for driving movement in single-celled organisms—think of how an amoeba moves by extending its cellular membrane. Cells in the brain aren’t mobile in the same sense, but pituitary cells use pseudopodia to coordinate with each other and move closer to blood vessels for hormone release. This study suggests that pseudopodia function differently in the pituitary glands of tame foxes than in aggressive ones. Hekman explains that this makes a lot of sense because tame and aggressive foxes actually produce similar amounts of hormones in the pituitary gland—the critical difference is in the amount that is released into the bloodstream.

Hekman is optimistic that a better understanding of these differences in foxes might reveal more about what’s going on in aggressive pets. A better understanding of the biological underpinnings of aggression could even have implications for the development of behavioral medication in the future. “It’s a correlational study; it’s a first step,” says Hekman, “The next step is to get living cells and put them through functional tests.” Though the study is an early investigation, it opens doors for future work that might point toward a pill for your pugnacious pup.

CITATION

Anterior Pituitary Transcriptome Suggests Differences in ACTH Release in Tame and Aggressive Foxes

Fruit fly mutants can sometimes be grisly. Ecdysteroid hormones control aspects of fly development, including molting and metamorphosis; because aberrations in these genes lead to embryos with a ghastly appearance, they have been collectively dubbed “Halloween genes.”

In a study published in GENETICS, Uryu et al. investigated how the expression of these genes is regulated. Halloween genes, such as spookier and neverland, are expressed in specific parts of the developing fly at specific times, suggesting that precise transcriptional programming is at play. Since some Halloween genes are regulated by zinc finger transcription factors like Ouija board and Molting defective, the authors explored whether other, structurally similar transcription factors in the Drosophila genome could also play a role.

Uryu et al. identified the novel transcription factor Séance as a regulator of Halloween genes. They found that Seance, Ouija board, and Molting defective collectively control the expression of spookier and neverland, which in turn regulate ecdysteroid synthesis. The cooperation of three transcription factors to modulate expression of just two genes underscores the critical importance of spatiotemporal regulation of gene expression.

As developmental genes are characterized and studied, our understanding of them continues to increase, hopefully making these sinister-sounding genes a little less scary. However, one burning question still looms: why do Drosophila genes get all the cool names?

CITATION

Cooperative Control of Ecdysone Biosynthesis in Drosophila by Transcription Factors Séance, Ouija board, and Molting Defective

Outa Uryu, Qiuxiang Ou, Tatsuya Komura-Kawa, Takumi Kamiyama, Masatoshi Iga, Monika Syrzycka, Keiko Hirota, Hiroshi Kataoka, Barry M. Honda, Kirst King-Jones and Ryusuke Niwa. 

Genetics February 2018 208: 605-62

https://doi.org/10.1534/genetics.117.300268

http://www.genetics.org/content/208/2/605

The Genetics Society of America (GSA) is pleased to announce that Job Dekker of the University of Massachusetts Medical School is the recipient of the 2018 Edward Novitski Prize. The award honors investigators who have exhibited “an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research.” Dekker, a Howard Hughes Medical Institute investigator, is recognized for scientific contributions that include the development of chromosome conformation capture—a technique that has revolutionized chromosome research.

Job Dekker

Chromosome conformation capture, or 3C, allows researchers to study the interactions of chromosomes at resolutions and scales previously impossible to attain. In 3C, chromatin is treated with a crosslinking chemical that causes chromosomal regions that are near each other to be chemically linked together. By isolating these crosslinked regions of chromatin and determining their DNA sequences, geneticists can deduce which parts of the genome are in proximity to each other. Although the foundation of the technique seems simple, no one before Dekker had formulated a practical way to take advantage of it for a high-throughput molecular assay like 3C.

Dekker developed the approach while he was working as a postdoctoral fellow in Nancy Kleckner’s lab at Harvard. His original aim was to create a method that would aid his research on homologous chromosome pairing, but he soon recognized that the new technique could be used for much more.

“His invented approach has ushered in a completely new era in the study of chromosomes; has impacted and stimulated diverse disciplines from cytology to molecular biology to polymer physics; and has revolutionized the fields of genomics and human genetics,” Kleckner says.

3C is now used in labs around the world and has spawned numerous spinoff techniques; some of the most exciting research employing these methods has come from Dekker’s own lab. His group found that, contrary to the then-popular idea that chromatin exists in an essentially randomly arranged blob, chromatin is actually organized into different types of domains and compartments. Chromosomal compartments allow massive amounts of chromatin to be spatially separated into distinct functional sub-nuclear neighborhoods, preventing inappropriate mixing of parts of chromosomes that are differentially regulated.

One of Dekker’s lab’s most influential findings is the discovery of topologically associating domains. These domains represent the structural and functional units of gene regulation: genes located within these domains are acted on by regulatory elements contained within these domains, while also being isolated from regulatory elements in other topologically associating domains.

The team also discovered how chromosomes become tightly packed into their recognizable rod shapes in preparation for mitosis. Further, Dekker and his group pioneered the use of chromosome conformation capture data to assemble the linear sequence of complete genomes.

The body of work produced in Dekker’s lab has led to his recognition as one of the most important investigators in his area of research. “In my opinion, Dekker is the very best scientist of his generation working in the chromosomes field. He would bring appropriate honor to the memory of Ed Novitski,” says Kleckner, who received the GSA’s Thomas Hunt Morgan Medal in 2016.

The Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity and intellectual ingenuity has been used to design and execute scientific experiments to solve a difficult problem in genetics. It recognizes the beautiful and ingenious experimental design and execution involved in genetics research. The Prize, established by the Novitski family and GSA, honors the memory of Edward Novitski (1918–2006), a Drosophila geneticist and lifelong GSA member who specialized in chromosome mechanics and meiosis through the construction of modified chromosomes.

The Prize will be presented to Dekker at the Annual Drosophila Research Conference in Philadelphia, which will take place from April 11^th–15^th, 2018.

When a noni fruit ripens, it stinks like old cheese—or even vomit. Familiar to many in the form of expensive juices sold as health supplements, this pungent fruit is engaged in a slow-motion arms race with would-be insect pests. Fruit flies are unable to feast on noni—scientific name Morinda citrifolia—because the fruit is dosed with large quantities of octanoic acid (OA), making it highly toxic to them. But one species has sidestepped this defense system: in tropical Seychelles, a specialized type of fruit fly called Drosophila sechellia has evolved to feed exclusively on the unappetizing fruit.

To learn how D. sechellia thrives on a diet that should kill it, Lanno et al. looked for D. sechellia genes that were differentially expressed when the flies were given OA-containing food. Their analysis revealed 104 differentially regulated genes that have known orthologs in the OA-susceptible fly D. melanogaster. Many of the downregulated genes are involved in the immune system—an interesting result given the recent finding that D. sechellia can’t mount an immune response to an attack by the parasitoid wasp Asobara tabida. The downregulated immune genes include some that are involved in responses to a variety of threats, including bacteria, so OA exposure may deal a major blow to the immune system.  

Among the upregulated genes are several in the insect-specific Osiris family. One of these, Osi6, is the only gene in the set of 104 that is found in a region of the genome known to have a major impact on OA resistance. This aligns with the research group’s previous discoveries that Osi6 expression is 72 times greater in D. sechellia than it is in D. simulans, an OA-susceptible fly, and that knocking down Osi6 in D. melanogaster makes it even more vulnerable to OA.

A different research group recently found that the Osiris gene cluster is under strong selection in an isolated population of the fly D. yakuba that has just begun adapting to a diet of poison-laden noni, another clue that learning more about these genes may be crucial for understanding OA resistance and this compelling model of ecological adaptation.

CITATION:

Lanno, S.; Gregory, S.; Shimshak, S.; Alverson, M.; Chiu, K.; Feil, A.; Findley, M.; Forman, T.; Gordon, J.; Ho, J.; Krupp, J.; Lam, I.; Lane, J.; Linde, S.; Morse, A.; Rusk, S.; Ryan, R.; Saniee, A.; Sheth, R.; Siranosian, J.; Sirichantaropart, L.; Sternlieb, S.; Zaccardi, C.; Coolon, J. Transcriptomic Analysis of Octanoic Acid Response in Drosophila sechellia Using RNA-Sequencing.
G3, 7(12), 3867-3873.
DOI: 10.1534/g3.117.300297
http://www.g3journal.org/content/7/12/3867

The yeast Candida albicans lives on and even inside many of us. Most of the time, its silent presence goes unnoticed, but this fungus can turn on its host, causing infections ranging in severity from annoying to life-threatening. For the yeast to become pathogenic, some of the C. albicans must transform from small, round cells into long, thread-like filaments, a process that can be triggered by environmental cues. To learn more about how these yeast morph, Azadmanesh et al. examined C. albicans filamentation under ten different conditions—and their results may have implications for the ways we study and treat infections.

C. albicans filamentation can be triggered by a variety of stimuli, from the surface the yeast are growing on to chemicals floating around them. Acidic environments, for example, make filamentation less likely, which is thought to be one reason maintaining a healthy balance of lactic acid-generating bacteria helps prevent vaginal yeast infections. Azadmanesh et al. determined which genes are required for filamentation under ten different environmental conditions, and for each condition, they also examined how gene expression changes during filamentation.

The researchers identified several genes needed for filamentation in all the conditions tested. In most cases, the reasons these genes are needed isn’t clear, but some have roles that make sense given what we know about how filamentation works. A few of the genes, for example, are involved in regulating the actin cytoskeleton, and modifications to the actin cytoskeleton are required for filamentation.

Surprisingly, though, the core genes required for filamentation under all conditions are the exceptions. Mostly, they found that both the genetic requirements for filamentation and the gene expression changes vary significantly in different conditions. This means that when researchers are comparing previous studies of C. albicans filamentation, they may not be comparing two like things: the programs of filamentation may be different in each case. The group’s work also has medical implications. The genes required for filamentation are different in solid and liquid media, suggesting that C. albicans infections in the gastrointestinal and genitourinary tracts are likely different from those found in bodily fluids like blood—which may be an important factor to consider when studying these infections and designing treatments.

CITATION:

Azadmanesh, J.; Gowen, A.; Creger, P.; Schafer, N.; Blankenship, J. Filamentation Involves Two Overlapping, but Distinct, Programs of Filamentation in the Pathogenic Fungus Candida albicans.
G3, 7(11), 3797-3808.
DOI: 10.1534/g3.117.300224
http://www.g3journal.org/content/7/11/3797