When female Anopheles mosquitoes take a blood meal from someone with malaria, a tiny Plasmodium parasite enters the mosquito’s digestive tract. That parasite can invade the mosquito’s salivary tissues, so when the insect takes another blood meal, the intruder can slip into the next human host and start a new malaria infection. Malaria is a life-threatening condition that infected 241 million people in 2020 and disproportionately affects vulnerable populations.

To combat the disease, researchers from the University of California, Irvine are developing genetically modified African malaria mosquitoes (Anopheles gambiae) that can’t transmit human malaria, alongside a gene-drive system that can quickly spread those genes and block the spread of the malaria parasite through the population. While this system usually operates with nearly 100 percent efficiency, a small number of mosquitoes will still wind up with mutant alleles that resist the gene drive. Could these mutant alleles sabotage the whole approach? In a paper published in GENETICS, Carballar-Lejarazú et al. looked at this phenomenon and found these mutations didn’t hamper the gene drive in their system.

Malaria-Resistant Mosquitoes

Contributing author Anthony James began exploring genetic methods for controlling vector-borne disease in the mid-1980s. Eventually he exploited mosquito genes that are only turned on in female mosquitoes after a blood meal and linked them with mouse antibodies that protect mice from human malaria parasites.

When these malaria-busting synthetic genes are inserted into mosquitoes, they can’t transmit malaria. And if it mates with a regular mosquito, the beneficial gene will be inherited like any other gene, gradually building up in the mosquito population. But what if that process could happen faster?

That’s when CRISPR gene editing technology hit the scene. “It seems like overnight when you work 10 or 15 years on something to make it work and then something new comes along and—in less than a year—you have it working,” says James.

Gene editing operates on the germline—the cells that will eventually become sperm or eggs—by snipping the normal chromosome and inserting the new sequence, in this case, the malaria fighting gene. In male mosquitoes, this works so well that each male passes on the new gene to nearly 100% of its offspring.

It’s a bit more complicated in female mosquitoes because egg cells are massive compared with sperm. When the system snips the normal chromosome and inserts the synthetic sequence, the second chromosome may be too far away to trigger the repair mechanism that sews the cut chromosome back up while including the system. That means there’s a chance the snipped chromosome will just stick itself back together—called nonhomologous end joining—possibly resulting in a mutant allele that resists the gene drive.

Exploring Gene Drive Mutations

To figure out if those mutant alleles could pose a problem for the gene drive system, the researchers linked the system to a somatic gene for eye color and marked it with a fluorescent protein. Then, the team performed various crosses to see how the genes passed on to future generations. Non-mutant progeny had black eyes (before adulthood) while those with the mutant allele had pink eyes. And all the progeny carrying the gene drive had eyes that fluoresced blue under light.

To make things a bit more complicated, some progeny were mosaics, with a mix of alleles and more complex eyes, but since the eye color gene isn’t part of the germline—it won’t pass on to the next generation—most of those mosaic mosquitoes still passed on the gene drive.

In the lab, about 25 percent of the first generation of progeny received the gene drive. By the fourth generation, the entire population had fluorescent blue eyes—meaning none of those mosquitoes could transmit malaria.

“Four generations is sufficient,” says James.  “That’s well short of one transmission season.”

James is quick to point out that this isn’t a magic bullet for malaria and there is more research to be done. There are also many thorny issues and debates for scientists and the broader community to work through before everyone is comfortable deploying gene drive mosquitoes in the wild. But James is hopeful the project to which he’s dedicated so many years may one day help ease the malaria crisis.

“There was a famous scientist who said a new idea doesn’t take hold because you change people’s minds; it takes hold because there’s a whole new generation of people that have grown up hearing about it,” says James. “I wish it was a little faster, but we’ll do our part, and hopefully people will take it up. It may not be me, but we have something to hand off.”

CITATION:

Cas9-mediated maternal effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae

Rebeca Carballar-Lejarazú, Taylor Tushar, Thai Binh Pham, Anthony A James

GENETICS

2022: iyac055

https://doi.org/10.1093/genetics/iyac055

Melissa Mayer is a freelance science writer based in Portland, Oregon.

Sexual reproduction is scarce in skin infection culprit.

While some people love to feel the burn during a workout, we generally seek that sensation in our muscles—not our feet. Treading barefoot in damp, communal environments like gym showers and the perimeters of pools can expose us to the fungus Trichophyton rubrum, the most common cause of athlete’s foot. Despite its name, athlete’s foot isn’t found exclusively in fitness fanatics—it affects around 15% of people worldwide. New work published in GENETICS shows that across this global range, the T. rubrum genome varies surprisingly little.

T. rubrum is widespread and comes in many varieties called morphotypes that differ in characteristics such as which parts of the body they can infect and the appearance of their colonies. In this study, the researchers found that T. rubrum samples from around the world were remarkably genetically similar to one another despite representing many different morphotypes. The data also suggest T. rubrum rarely, if ever, sexually reproduces. Mating in many fungi occurs between cells of different mating types, but of the 135 samples tested, the mating types of all but a single Mediterranean strain were identical.

The researchers found no evidence of mating when they paired the Mediterranean strain with strains of the opposite mating type, which supports the idea that the fungi reproduce clonally. This result comes with some caveats, though: the lab conditions may not have favored mating, and it’s possible that mating does occur when the Mediterranean strain comes in contact with some of the other strains in the wild. Overall, the results are consistent with one hypothesis that has been put forth about the fungi, which that is the species recently experienced a sharp decrease in sexual reproduction. The authors suggest this might have occured when T. rubrum began specializing for growth on humans.

Given that pathogens must dodge the defenses of their constantly adapting hosts, it may seem strange that T. rubrum exhibits such low genetic diversity, but it’s not alone in this trait. For reasons that haven’t been fully established, bacteria that cause tuberculosis and Hansen’s disease (leprosy) also come in a variety of types despite being highly clonal.

Although T. rubrum infections are treatable and rarely progress to serious disease, they’re common and often extremely uncomfortable. Those of us who wear sandals in the gym shower would certainly agree it’s well worth it to learn more about how this pesky fungus operates.

CITATION:

Whole-Genome Analysis Illustrates Global Clonal Population Structure of the Ubiquitous Dermatophyte Pathogen Trichophyton rubrum
Gabriela F. Persinoti, Diego A. Martinez, Wenjun Li, Aylin Döğen, R. Blake Billmyre, Anna Averette, Jonathan M. Goldberg, Terrance Shea, Sarah Young, Qiandong Zeng, Brian G. Oliver, Richard Barton, Banu Metin, Süleyha Hilmioğlu-Polat, Macit Ilkit, Yvonne Gräser, Nilce M. Martinez-Rossi, Theodore C. White, Joseph Heitman, Christina A. Cuomo
GENETICS 2018 208: 1657-1669; https://doi.org/10.1534/genetics.117.300573
http://www.genetics.org/content/208/4/1657

[wysija_form id=”1″]

Biolistic genetic transformation in C. neoformans produces few off-target side effects.

While genome editing is a staple of genetics research, there remains anxiety about unintended side effects of genetic transformation, one of the most common longstanding genome-editing techniques. Some researchers fear that the process of introducing exogenous DNA into a cell may cause unwanted mutations, adding confounding variables to their experiments—but others aren’t content to accept this lore.

In G3, Friedman et al. report their study of the off-target effects of transformation in the common fungal pathogen Cryptococcus neoformans. They created 23 new strains using biolistic transformation, a standard procedure for this organism that involves shooting gold beads coated with DNA into cells, to add a marker to a neutral site in the strains’ genomes. They then sequenced the genomes of these new strains. Across all 23 strains, they found only four point mutations; of these, just one changed an amino acid in the encoded protein. They also found one case of insertion of a second, partial copy of the drug resistance marker.

They used the same transformation method to create more than 100 strains, each with a single gene replaced by a marker gene. By carrying out RNA-Seq on this group, they identified six strains that expressed the marker at unusually high or low levels. On average, these outlier strains had 1.67 off-target point mutations, and three of them (50%) carried multiple copies of the marker. The greater number of mutations in these six strains compared to the first set of 23 likely reflects selection for mutations that compensate for the genes the researchers replaced. Nonetheless, the overall number of off-target effects was still low, and the authors write that the mutations would be unlikely to have consequences as drastic as deleting the intended gene would. Therefore, they argue, effects observed when a gene is deleted using this protocol are likely most often due to the deletion and not to off-target effects, although additional confirmation of any deletion’s effects is still prudent.

The study illustrates the importance of testing conventional wisdom, and it will be important to investigate whether these findings apply to other species used in research and other transformation techniques. In the process of conducting this study, the researchers also sequenced a frequently used C. neoformans laboratory strain’s genome—a vital resource because this fungus is estimated to kill hundreds of thousands of people each year.

CITATION:

Unintended Side Effects of Transformation Are Very Rare in Cryptococcus neoformans
Ryan Z. Friedman, Stacey R. Gish, Holly Brown, Lindsey Brier, Nicole Howard, Tamara L. Doering and Michael R. Brent
G3: GENES|GENOMES|GENETICS 2018 8: 815-822; https://doi.org/10.1534/g3.117.300357
http://www.g3journal.org/content/8/3/815

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

When a group of microorganisms needs to stick together, they build a biofilm. The cells cement themselves together onto a surface, forming durable structures that are notoriously hard to remove. In a medical setting, biofilms can contribute to dangerous antibiotic resistance. In the August issue of G3, Cromie et al. use a yeast model to identify six genes involved in biofilm formation, providing new leads for methods to combat biofilm-forming pathogens.

When forming a biofilm, microorganisms have to transition from a solitary lifestyle to one anchored down and surrounded by companions. This requires substantial changes in gene expression. To identify genes whose regulation contributes to biofilm formation, the authors used a genome-wide overexpression screen in a yeast strain that naturally forms biofilms. They examined 4,600 colonies that had been transformed with plasmids carrying individual yeast genes, looking for a change from the “fluffy” biofilm colony structure to the smooth unstructured globs typical of laboratory yeast. In the end, they identified six genes whose overexpression disrupted biofilm formation, causing colonies to change from fluffy to smooth.

Interestingly, all six of these genes are regulatory proteins—and four of them are transcription factors. To investigate the gene network changes triggered by overexpression, the authors performed RNA-seq on the six transformed yeast strains. They found evidence that the same transcriptional network was activated by overexpression in five of the six strains, and this network contains some genes already known to affect colony morphology.

Expression levels of these regulators may act as a switch that yeast that can use to easily transition between growing in a solitary state and growing as a biofilm. Targeting these switches might be one way to prevent pernicious biofilms from forming in the first place.

CITATION

Transcriptional Profiling of Biofilm Regulators Identified by an Overexpression Screen in Saccharomyces cerevisiae

Gareth A. Cromie, Zhihao Tan, Michelle Hays, Amy Sirr, Eric W. Jeffery and  Aimée M. Dudley

G3: GENES, GENOMES, GENETICS August 1, 2017 vol. 7 no. 8 2845-2854; https://doi.org/10.1534/g3.117.042440

http://www.g3journal.org/content/7/8/2845

Taking probiotics might be the latest health fad, but for people with inflammatory bowel diseases, the microbiome is a more serious matter. With these autoimmune diseases, the composition of the gut microbiome can have critical health consequences. In the June issue of GENETICS, Mistry et al. use fruit flies to determine whether immune system activity affects the composition of the gut microbiome. They found that flies with compromised immune systems had a similar microbiome to their healthy relatives, but flies with overactive immune systems had distinctly different microbiome compositions and more gut microbes overall. This work suggests that the interaction between the immune system and the gut microbiome is a two-way street.

As a fruit fly ages, the species composition of its gut microbiome changes Young flies have diverse microbiomes that vary with their genotype and environment, but as they mature into adults, the composition converges on a typical makeup. In this study, Mistry et al. surveyed microbiome composition across the lifespan of flies with healthy, compromised, or constitutively active immune systems while controlling for bacterial transmission from the mother—the most important initial source of microbiome bacteria.

Overall, their results revealed that a constitutively active immune system has a much larger impact on gut microbiome composition than an underactive immune system. In normal conditions, flies with an immune deficit develop the typical adult microbiome more rapidly and end up with a higher density of microbes but are otherwise similar to healthy flies. Only flies whose maternally introduced microbes were eliminated showed a difference in microbiome composition.

In contrast, flies with an overactive immune system maintained very different microbiome diversity to normal, even for those exposed to their mother’s microbes, indicating that constitutively active immunity has a powerful impact on the microbiome. The authors also found that when these flies were co-housed with healthy flies, the microbiomes of the healthy flies become more similar to those with overactive immune systems.

One possible explanation is that constant immune activity triggers inflammation in the gut, creating an aerobic environment that cultivates a different variety of bacteria than a healthy intestinal tract. Human conditions like Crohn’s disease and ulcerative colitis are characterized by constant inflammation and have been linked to changes in the gut microbiome. In fact, some types of bacteria commonly found in these patients were the same as those identified in the flies with overactive immune systems, suggesting Drosophila may prove a useful model for these debilitating diseases.

Interaction Between Familial Transmission and a Constitutively Active Immune System Shapes Gut Microbiota in Drosophila melanogaster.

Rupal Mistry, Ilias Kounatidis and Petros Ligoxygakis

GENETICS. June 1, 2017 vol. 206 no. 2 889-904; https://doi.org/10.1534/genetics.116.190215

http://www.genetics.org/content/206/2/889

In the ruins of the Chernobyl Nuclear Power Plant—an area deemed unsafe for humans for the next 20,000 years after a catastrophic failure—life thrives. Fungi that reside there, along with other organisms that can survive large radiation doses, must have strategies to cope with the DNA-damaging effects of living at a meltdown site. In the April issue of GENETICS, Repar et al. report that radiation-resistant prokaryotes tend to have higher rates of genome rearrangements—a sign of improperly repaired double-strand breaks in DNA—than related species do, meaning that even these hardy organisms can’t fully prevent or fix radiation-induced DNA damage.

The failure to repair all DNA damage doesn’t result from lack of trying. Prior research showed that Deinococcus radiodurans, one of the most radiation-resistant organisms identified to date, has a special method for repairing double-strand breaks in DNA, and along with several other radiation-resistant prokaryotes, it can patch its genome back together after hundreds of double-strand breaks. Variation in the DNA repair machinery is under positive selection in radiation-resistant bacteria but not in related nonresistant bacteria, indicating that there’s a need to optimize these genes’ functions to cope with radiation.

Despite their adaptations to radiation bombardment, these species’ genomes are more shuffled around than their more radiation-sensitive relatives’ are. This suggests it’s not possible to prevent or patch up all the damage, even with super-charged DNA repair, but it’s also conceivable that the increased rate of genome rearrangements might actually be beneficial in conditions of stress. The rearrangements could cause mutations that allow the radiation-resistant organisms to survive in their dangerous environments. But Repar et al. found that radiation-resistant organisms were no different from their nonresistant cousins in selection for genome organization (i.e., against genome rearrangements), implying that their high rate of rearrangements does not affect their ability to adapt to radiation stress. Ultimately, although these extremophiles are uniquely skilled at fixing their genomes, they still end up with battle scars.

CITATION:

Repar, J.; Supek, F.; Klanjscek, T.; Warnecke, T.; Zahradka, K.; Zahradka, D. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.
GENETICS, 205(4), 1677-1689.
DOI: 10.1534/genetics.116.196154
http://www.genetics.org/content/205/4/1677

Two highly similar genes that contribute to drug resistance in a pathogenic yeast have been co-evolving as tandem duplicates for the past 134 million years—while maintaining distinct functions. This is the conclusion of a paper in the April issue of GENETICS by Lamping et al. that examines the evolutionary effects of ectopic gene conversion.

Evolutionary change can take a big step forward when a gene is duplicated within a genome. Gene duplication allows the new gene copy to diverge in function from the original, enabling new adaptations and innovations while preserving the ancestral activity. But duplicates can also be prevented from evolving differences because their sequence similarity encourages ectopic gene conversion, which transforms stretches of very similar sequence into identical matches. Normally, gene conversion corrects mismatched alleles that pair during meiosis; the process replaces the sequence from one allele with the corresponding part of the other allele, making the short paired region identical. Ectopic gene conversion (ECG) occurs between duplicated genes at separate loci that can undergo a similar gene conversion because of their high sequence similarity.

The similarity of tandem duplicates can make sequence analysis of the individual genes tricky. The authors tackled this task by analyzing the evolutionary patterns of two drug efflux pumps in Candida krusei, a disease-causing fungus that is naturally resistant to common antifungal drugs. Some of this yeast’s innate resistance comes from the activity of these two proteins, which pump toxic drugs out of the cell. The pumps arose from a tandem duplication event and have slightly different functions: one is more efficient at pumping out small molecules while the other specializes in removing larger compounds. By splitting the responsibility for pumping large and small molecules between the two gene products, natural selection enabled more efficient pumping of individual compounds by specializing each gene for its particular function.

The authors identified EGC events and small regions with adaptive differences between the two efflux pump gene duplicates by examining the sequence polymorphism of 30 different alleles of the two genes from seven different strains of the diploid C. krusei. Overall, a very high frequency of EGC events between both duplicates was indicated by low polymorphism. They detected EGC events by identifying alleles with shared nucleotide changes at the two separate duplicate loci. This copy/pasting process between highly similar sequences is clearly an important contributor to the evolution of these genes, as over 90% of the two duplicates were identical.

This similarity makes it even more remarkable that six short sections of DNA never experienced EGC, but instead they maintained distinct sequences between the two duplicate efflux pump genes. These differences cause changes in the protein sequence of the efflux pumps, particularly in the region that spans the cell membrane. Natural selection seems to be protecting these key functional differences from EGC, allowing the two copies to evolve specialized abilities in pumping molecules in and out of the cell. Comparing the sequence data from C. krusei with other species showed that the efflux pumps have been evolving together through EGC for roughly 134 million years. Lamping et al.’s work shows that though this force strongly pushes tandem duplicates towards similarity, natural selection is perfectly capable of pulling them back apart to fill unique adaptive roles.

http://www.genetics.org/content/205/4/1619

Lamping, E., Zhu, J. Y., Niimi, M., & Cannon, R. D. (2017). Role of ectopic gene conversion in the evolution of a Candida krusei pleiotropic drug resistance transporter family. GENETICS, 205(4), 1619-1639.

To the unaided eye, Antarctic soil and alpine glaciers may appear to be barren wastelands devoid of life. But some microbes call hostile habitats like these home. Research on one such organism, published in the latest issue of G3, reveals some of the mechanisms behind cold adaptation—and explains why these otherwise hardy creatures can’t survive at temperatures that would be comfortable for us.  

The research’s star subject is Mrakia psychrophila, a type of yeast found on the Tibetan Plateau that grows best at 12-15°C (54-59°F) and cannot grow over 20°C (68°F). Cold stress is distinct from cold adaptation—cold stress occurs when an organism is transferred from a higher temperature to a lower temperature over a short time, while cold adaptation (the process at play in M. psychrophila) is a steady-state phenomenon that occurs when an organism is kept at a cold temperature over an extended period.

By sequencing the cold-adapted yeast’s genome and comparing it to those of organisms that grow at moderate temperatures (mesophiles), high temperatures (thermophiles) and others that grow at cold temperatures (psychrophiles), the researchers observed some interesting trends. Like many cold-adapted and cold-tolerant microbes, the fungus exhibits high expression of genes involved in producing unsaturated fatty acids, which are critical for keeping membranes fluid at low temperatures. One major difference between M. psychrophila and other organisms is a bias in codon usage. This may influence mRNA structure, which also depends on temperature.

Comparing the transcriptome and proteome of the fungus when grown at different temperatures unveiled other secrets behind its adaptation to cold. Alternative splicing is highly influenced by growth temperature in this yeast. Genes related to energy metabolism are also upregulated in response to cold in M. psychrophila, in contrast to the mesophilic bacterial species Pseudomonas putida, which previous research showed conserves energy under cold stress. An increase in functions related to energy metabolism may reflect a greater need for ATP to fuel processes such as biosynthesis of unsaturated fatty acids.

Most intriguingly, the researchers found that at 20°C (68°F), M. psychrophila showed evidence of endoplasmic reticulum (ER) stress, a state characterized by the accumulation of unfolded proteins in the ER. This could explain why the fungi can’t tolerate moderate temperatures: ER stress, if not relieved, can induce cell death.

In addition to apparent quirks of M. psychrophila, these findings shed light on what may be some common mechanisms of cold adaptation. But that’s not all: research on psychrophilic organisms also informs the field of astrobiology, which aims to understand what life on other planets, if it exists, might be like. So while these researchers focused on an exotic yeast, the implications of their findings could be out of this world.

CITATION:

Su, Y.; Jiang, X.; Wu, W.; Wang, M.; Hamid, M. I.; Xiang, M.; Liu, X. Genomic, Transcriptomic, and Proteomic Analysis Provide Insights into the Cold Adaptation Mechanism of the Obligate Psychrophilic Fungus Mrakia psychrophila.
G3, 6(11), 3603–3613.
DOI:10.1534/g3.116.033308
http://g3journal.org/content/6/11/3603

In the fast-paced life of a bacterium, the ability to manufacture proteins quickly and efficiently is crucial. In these organisms, mRNAs—the templates for building proteins—have a string of bases near the start called the Shine-Dalgarno (SD) sequence. This motif increases the rate at which translation is initiated. Some results suggest that the presence of SD sequences further into an mRNA, in the coding region, actually slow the elongation rate—but work by a few other groups does not support this claim.

In the November issue of G3, Yang et al. reason that if SD sequences do slow elongation, there should be fewer of the sequences than would be expected (given codon use biases) in the coding regions of bacterial mRNAs. Using data from many species of bacteria, they found that not only are SD sequences rarer in coding regions, but they are also even more depleted in the genes that are most expressed—and the effect was greatest in the bacteria with the shortest generation times.

In addition to slowing elongation, there are a few other possible explanations for the dearth of SD sequences in coding regions. The sequences may be mistaken by ribosomes for translation start sites, resulting in truncated proteins, or they may cause ribosomes to slip up and result in a frameshift. It’s also possible that the ribosomes get stuck on the SD sequences, leading to a reduced pool of ribosomes available to start translation.

If SD sequences are so detrimental in this context, it might seem strange that the coding regions of bacterial mRNAs would have any SD sequences at all. But natural selection typically keeps bacterial genomes small—a trim genome allows bacteria to replicate quickly and potentially beat out its competitors—so it’s possible that the initiation sites for a gene might need to overlap with the end of the prior gene in the operon. And despite being potentially harmful, random mutations ensure that some of these misplaced sequences will arise by chance.

An important implication of this work is that the presence or absence of SD sequences within coding regions is a significant modulator of translation efficiency. So far, much research has been dedicated to codon usage as the primary contributor to translation speed, since codons calling for rarer tRNAs might take longer to be translated. But according to these researchers’ results, SD sequences in coding regions also have a significant effect. This implies that when designing artificial genes to insert into bacteria, researchers might want to avoid including SD sequences if they hope to get the highest protein yield. Thinking like a bacterium may not sound like a good strategy for a scientist, but after being molded by billions of years of competition with their fellow microbes, these organisms do seem to have learned a trick or two.

CITATION:

Yang, C.; Hockenberry, A.; Jewett, M.; Amaral, L. Depletion of Shine-Dalgarno Sequences within Bacterial Coding Regions Is Expression Dependent.
G3, 6(11), 3467–3474.
DOI:10.1534/g3.116.032227
http://www.g3journal.org/content/6/11/3467