We are all familiar with the conditioning or deconditioning of muscles that occurs in response to exercise or lack of exercise. When maintained over an evolutionary timescale spanning years, it leads to dramatic changes in muscle mass, metabolism, and even animal biochemistry. It reveals how some super athletes and couch potatoes can tune their metabolic pathways in their muscles to efficiently break down sugar or store it to suit their unique lifestyles.
First, let’s look at the super athletes. The seemingly effortless hovering flight of a hummingbird is accomplished by burning sugar in its flight muscles at breakneck speed. But how such adaptations evolved is a challenge to reconstruct. A team of German researchers recently suggested the loss of a key gene. FBP2. Without it, birds break down sugar and use it for energy more efficiently. Researchers learned this by comparing the age of key hummingbird fossils to the time of gene loss. chemistry.
“All hummingbirds are hovering-flyers, and all hummingbirds are nectars. After they split from another avian lineage, the swifts, hummingbirds radiated to the 300 or so species that exist today. Earlier, in a branch of the tree of evolution, he explains.
This new trait allows hummingbirds to perform their characteristic airborne flight. This makes the hummingbird extremely mobile, allowing it to remain nearly motionless in the air while drinking the nectar of flowers, the main source of energy for its diet.
To better understand the origin of this unique ability, Hiller’s team sequenced the genome of a hummingbird species that is a relatively distant cousin of other hummingbirds. By matching this to two existing hummingbird genomes (Anna’s Hummingbird and Black-breasted Hillstar), the researchers were able to identify genetic alterations that occurred in all hummingbird ancestors. Hiller reasoned that hovering flight must have evolved elsewhere in its ancestral branch, and that genetic changes that occurred there may have contributed to the evolution of this trait.
By comparing the hummingbird genome to the chicken genome, researchers identified five genes that the hummingbird was missing. FBP2, It has long been known to be involved in glucose metabolism. Sugar circulating in the blood is taken up by cells. And once inside, sugars are broken down by enzymes in a process called glycolysis. This creates two molecules, each carrying her three carbon atoms and two ATP molecules, which cells use as fuel in all sorts of processes, including muscle contraction. These biochemical reactions proceed in both forward and backward directions. The reflux that takes in two 3-carbon molecules to make a sugar is called gluconeogenesis. FBP2 It encodes an enzyme in muscle cells that catalyzes this reversal of glycolysis.
In typical muscle tissue, this enzyme takes up small carbon molecules to make sugars.but the hummingbird lost FBP2, That is, their muscles cannot catalyze the synthesis of sugars from small carbon molecules, Hiller and his colleagues FBP2 It makes the correct sugar reaction more efficient and accelerates the hummingbird’s ability to break down sugar. Sugar is abundantly consumed by the nectar diet.
To test this idea, they had to conduct an experiment. They were constrained by the fact that it is nearly impossible to genetically engineer a live bird such as a chicken to knock it out. FBP2 Measure the effect.Instead, researchers used a quail muscle cell line to knock it out FBP2They next measured the rate of glycolysis in quail muscle cells and showed that the process actually ran faster when the gene was knocked out. FBP2 The knockout also had more mitochondria for reasons that are not yet fully understood. ‘ says Hiller. “The effect we saw [in the cell line] At least consistent with observations of hummingbird muscles. “
Further genomic analysis has led the researchers to FBP2 It must have happened 46 to 34 million years ago. This estimate was consistent with paleontological evidence that emerged in the form of two important fossils of him found in Germany about 20 years earlier. One fossil that still looks like a Swift, he is 48 million years old, and the other is an early fossil of a branch of the Swift lineage, showing a change in the bony composition of the shoulder girdle. biomechanically possible. of hovering flight. As such, it is the oldest known hummingbird, about 35 million years old to he is 30 million years old.
Estimated age similarity FBP2 Mutation and fossil dating are compelling evidence that this mutation contributed to hovering flight, says Hiller. This adaptation required several steps, including changes in the shoulder girdle. It’s one of the knobs that Evolution has adjusted for,” Hiller says. “It probably took a few steps or many, and we think this is one of them.”
In fact, evolution can tailor key metabolic pathways in different ways to suit the demands of a particular environment. Mexican cave fish, which live in dark caves, have a different kind of metabolic problem. has undergone many changes. For one thing, they have no predators, which made them swim slower compared to the surface fish they evolved from.
“We know that if humans reduce their exercise for just a day or two, it can have serious effects on their muscles,” says Luke Olsen, a graduate student at the Stowers Institute in Missouri. increase. Proceedings of the National Academy of Sciences January 24th. “If you think about the bloodline, how did the muscles change over the course of 160,000 years if they were less mobile?”
Muscle is very important for regulating metabolism throughout the body,” explains Trey Wright, who studies animal physiology at the University of Texas Medical School in Galveston. “In many animals, muscle mass can make up 40-50% of body weight and is a very metabolically demanding tissue. Regulating muscle metabolism has many implications for animal fitness. increase.”
To better understand the consequences of muscle mass loss in blood vessels, Olsen and his colleagues dissected muscle fibers from both blood vessels and surface fish and stimulated them electrically. The researchers found that cave fish muscle fibers contract with less force than surface fish muscle fibers. “This is a very important point because that’s exactly what we see in obese people,” says Olsen.
To test whether this actually leads to the fish’s inability to swim at high speeds, the team created a swimming tunnel. It’s like a treadmill for fish, allowing them to swim against water currents of varying speeds. He gradually increased the flow until his veins tired. Surprisingly, cave fish could swim as fast and as long as surface fish. Olsen and his colleagues hypothesized that large amounts of sugar stored as glycogen in cave fish muscles provide the energy needed to maintain muscle contraction during swimming endurance tests.
As expected, pre-exercise cave fish had more intramuscular glycogen than surface fish, but glycogen levels dropped sharply after the swim test. When they looked at what was happening chemically, they found elevated levels of both the enzymes that store glycogen and the enzymes that break it down. Her one of these enzymes, phosphoglucomutase 1 (PGM1), was activated by phosphorylation (addition of phosphorylated chemical groups), but not in marine fish. In fact, two of the bloodstream phosphorylated sites on this enzyme are mutated in humans with glycogen storage disease. In humans, when PGM1 is mutated at one of these sites and fails to phosphorylate, it causes the person to fatigue easily, explains Olsen. These same sites are hyperphosphorylated in cave fish, which may explain why they are slow to fatigue during swim tunnel experiments.
The researchers then focused on a specific phosphorylation site and created mutations that prevented that site from being phosphorylated. Cells with this mutation have lost much of their ability to make glycogen.
“What this tells us is that this particular site found to be hyperphosphorylated in the bloodstream leads to a change in PGM1 activity that takes in incoming glucose and converts it to glycogen. says Olsen. Increased PGM1 activity increases the muscle’s ability to generate and store glycogen. This explains why fish muscles contain a lot of glycogen.
Olsen and his supervisor at the Stowers Institute, Nicolas Rohner, believe this is adapted to cave fish. To stay in the cave, cave fish must swim against these currents. If they are swept out of the cave, they will not survive. So their metabolism must allow them to store energy to sustain for long periods without food, and then release the energy to enable them to swim against strong currents once in a blue moon. No. It does just that by phosphorylating PGM1, which increases its ability to store glycogen that can be broken down when needed.
Interestingly, according to Olsen, diabetics and obese people have increased inflammation, whereas blood vessels do not, even though their muscles contain a lot of fat and sugar. That’s it. Researchers are interested in better understanding how blood vessels were healthy even though muscle evolved to store more fat and sugar.
Misty Riddle, a Mexican bloodline researcher at the University of Nevada, said muscle wasting and the accumulation of sugar and fat are harmful to humans. However, in its unique environment it is beneficial to the bloodline.” [an] Studying bloodlines and their favorable traits could potentially be relevant to understanding how problems that arise when humans possess those traits can be mitigated.” she says.
Two studies show two extremes of evolution. In hummingbirds, a key gene for gluconeogenesis is missing, making the muscles very efficient at breaking down sugars for the energy needed for hovering flight. In contrast, the Mexican bloodline modified an enzyme that allowed muscles to efficiently store sugar as glycogen. In both cases, evolution adjusted the pathways that break down and store sugars, enabling new metabolic functions that help animals survive in harsh environments.
