What happened to the discovery of snake genes from frogs? Not surprisingly, this is the horizontal transfer of genes. In recent years, researchers have discovered many phenomena of horizontal gene transfer, not only in prokaryotes such as bacteria, but also in eukaryotes, and even between plants and insects. This may be the wisdom of survival.
Written by | Gu Shuchen
You may have seen "Shared XX" a lot, but have you heard of "Shared Genes"? In fact, some genes in our bodies may be similar to species such as lizards, frogs, crabs, and even sea urchins, and even genes in some organisms are transferred from other organisms! Although such gene "transfer" seems incredible, in fact, gene transfer between species is a frequent occurrence in the process of biological evolution. In nature, this mode of transmission of genetic material is called horizontal gene transfer (HGT).
Compared with the horizontal transfer of genes, we are more familiar with another way of gene delivery: vertical gene transfer (VGT). Parents pass on their genetic material to you, from you to your children, and the children and grandchildren are infinitely poor. This phenomenon of genetic material being passed on from generation to generation with the reproductive process is the "vertical transmission" of genes, and it is also the most extensive transmission method of genetic material in nature.
Horizontal gene transfer refers to the transfer of genetic information between biological organisms that are related or far or near, unlike the conventional vertical gene transmission from parents to offspring. Horizontal transfer of genes across species was once thought to occur only between microbes, but thanks to the development of sequencing technology, there is growing evidence that this process has been going on throughout the tree of life, and more horizontal transfer of genes has been confirmed in the past decade. And this phenomenon occurs not only in prokaryotes (some prokaryotes contribute up to 25% of genes to horizontal transfer [1][2, 3], but even in eukaryotes [4] and between the two [5]. And the genetic material that undergoes horizontal gene transfer is not only DNA, but also mRNA [6], and even entire organelles [7].
Recently, researchers discovered that Bovine-B (BovB), a gene that originated in snakes, has repeatedly jumped over barriers between species into frogs around the world, and this phenomenon appears to occur much more frequently in Madagascar than elsewhere. After carefully studying the genomes of frog and snake species around the world, scientists published a paper in Molecular Biology and Evolution in April 2022 stating that the gene somehow traveled from snakes to frogs at least 50 times on Earth [8]. But in Madagascar, the gene is being transferred with alarming frequency: 91 percent of the frog species there are present with the gene. Madagascar seems to have a particular incentive to facilitate the flow of the gene, and scientists believe that horizontal transmission of genes may occur more frequently in some places, and the ecology may have played an important role in this.
Genes originating in snakes have crossed species many times into frog genes around the world. Image credit: Fahmi Bhs
Nature's GMO art
Horizontal transfer of genes is common in bacteria. Prokaryotes like bacteria, whose DNA is bare, ring-shaped in different sizes, are more prone to gene transfer. Especially in the process of replication, bacteria copy genes from other species to adapt to changes in the environment. This is one reason why bacteria are prone to antibiotic resistance: drug resistance genes are easy to be transmitted horizontally, and bacteria are under the pressure of antibiotic selectivity, bacteria with antibiotic resistance genes will multiply, while bacteria without genetic mutations will die, and slowly drug-resistant bacteria gradually replace the original flora as the main flora. Bacterial gene exchange is so frequent that some scientists have even proposed that bacteria form a network of life-related species, rather than a family tree of individual bacteria.[9]
The cells of eukaryotes are different from prokaryotes such as bacteria, which protect the genome with fortress-like nuclei. In eukaryotes, DNA is carefully coiled around the nucleus, and only when needed will one of the genes be called up with the corresponding enzyme. But in recent years, examples of horizontal gene transfer involving eukaryotes have been discovered. For example, a paper published in March 2021 in Trends in Genetics confirmed that the icy water of the Arctic, North Pacific, and North Atlantic icy water Osmerus mordax acquired a gene from Clupea harengus in the same waters, which allows its blood to not freeze[10], allowing it to survive in cold water.
Herring (top) and smelt (bottom) are both cold-water fish that carry the same genes that allow them to survive in cold water. Photo by Four Oaks & Jack Perks
What's even more amazing is that sometimes the horizontal transmission of genes is also passed between animals and plants across different species. In the March 2021 issue of the journal Cell, it was reported that mainland scientists had made this amazing discovery after 20 years of tracking and research. They found that Bemisia tabaci, the only "super pest" identified by the Food and Agriculture Organization of the United Nations (FAO), actually obtained a new gene from plants through horizontal gene transfer, and used this new gene to bypass the plant's defense system, allowing the whitefly to successfully parasitize on many plants. This may be the reason why whiteflies can make waves around the world, causing great damage to many plants such as tomatoes, cucumbers, beans, cotton, etc.[11].
From the above studies, it can be found that horizontal gene transfer can help different species skip the slow process of obtaining new genes through mutation or recombination, and accelerate the innovation and evolution of the genome. But not all newly transferred genes will function in organisms. One example is BovB, which was first discovered in cows and later shown to jump between bizarre combinations of animals, and is not a functional gene in the traditional sense — it simply has the ability to copy its DNA sites to other locations at will. While it cannot be ruled out that BovB may also perform certain functions to benefit frogs, it is more likely that BovB is actively jumping between species to maintain its persistence simply because of its own strong ability to replicate itself. As depicted in The Selfish Gene, everything the BovB gene does is to maximize its chances of survival. This helps explain why jumping genes like BovB are always involved when eukaryotes are with the genetic material of other organisms.
Viruses help spread
Reading this, you must be curious about how eukaryotes actually transfer genes at the level. Unfortunately, at the moment we are not very clear about the mechanism of specific horizontal transmission. But after all, horizontal transfer really happened, and there must be something that helped the gene transfer. Scientists have found that viruses are indeed a tool that can help transfer genes at the level. Viruses, especially retroviruses, have the ability to enter the host cell and even the nucleus, they are able to insert genetic material into the host's genome. In fact, about 8% of the DNA in our human genome comes from viruses, which are also fragments left by ancient humans after being infected by viruses.
In addition, the horizontal transfer of genes achieved by the virus is also mutual, that is, not only the host will acquire new genes from the viral gene transfer, but the virus will also acquire the host's genes. A paper published in Nature Microbiology in December 2021 presented for the first time a comprehensive analysis of gene horizontal transfer between 201 eukaryotes and 108,842 viruses [12]. They found evidence of more than 6,700 gene transfers, in which host-to-virus transfers were about twice as high as virus-to-host transfers. Therefore, the researchers believe that horizontal gene transfer is the main driver of evolution on both sides. Viruses infect their hosts more efficiently through the eukaryotic genes they obtain, and eukaryotes use viral genes to acquire new traits.
The involvement of viruses also provides a possible explanation for the horizontal transfer of genes between eukaryotes. In eukaryotes, transferred genes need to pass through a series of obstacles. First, they must travel from the donor species to the new host species. They must then enter the nucleus of the host species and make their home in the genome. It is even more difficult to pass on the transferred gene to offspring, which means that the horizontally transferred gene must be inserted into the germ cells of the host species, such as sperm or eggs. And the involvement of the virus will make this process more likely. Small organisms such as Nematode, for example, have their reproductive tract and germ cells close to the intestine, and viruses that settle in the intestine are likely to bring genes into the germ cells. Frogs release eggs and sperm into the water when they breed, and these cells can acquire certain new genes through viruses in the surrounding environment. In some large organisms, such horizontal transfers may also be easier than we think. Some viruses specifically infect germ cells, and they facilitate the transfer of genes to germ cells at the level.
Scientists believe that we can think of horizontal gene transfer as the result of a combination of an organism and other organisms associated with or parasitic with it, as well as the natural ecological environment. Horizontally transferred genes tend to provide a survival advantage to the host organism, so the occurrence of this phenomenon is closely related to the specific environment in which the organism is located. However, the acquired genes also change with the transformation of the environment, and when the transferred genes no longer provide favorable living conditions, they are also lost [13].
Ecological impact
To find out how often genes are passed at the level, scientists took frog samples from around the world for DNA sequencing. They found that 50 of the 149 frog species outside Madagascar had the BovB gene. Of the 32 species of frogs originating in Madagascar, 29 carry the gene. Frogs in Madagascar acquire significantly higher rates of horizontal gene transfer than in other parts of the world.
The scenery of Madagascar, an African island country, shows the famous baobab tree. Photo by Bernard Gagnon
What are the particular factors in Madagascar's environment that make horizontal gene transfers occur so frequently? At present, scientists do not have an accurate answer to this question. The authors speculate that snakes living in Madagascar may carry the same BovB gene as snakes in other parts of the world, and they are more likely to enter new hosts. In addition, the island of Madagascar is rich in parasites, such as leeches that feed on the blood of other animals, which may bring snake blood containing the BovB gene into frogs. Or genes are transferred to the leech's genome and then into the frog with the help of viruses or other microorganisms.
Snake BovBs through the parasite's transmission route. Image source: References [8]
In addition, they found that at least two frog strains had BovB genes acquired after their ancestors migrated from Africa to Madagascar. From this point of view, the rate of horizontal gene transfer is not average, and it varies greatly in different geographical environments. Scientists believe that if more research can be done to observe the phenomenon of gene transfer on a global scale, and look at the speed of gene transfer between different regions, we may be surprised to find that the influence of geographical factors on horizontal gene transfer may be more important than we think.
But it is not easy to capture and confirm the process of horizontal gene transfer - DNA sequences may mutate during transmission to disguise their identity and erase traces of their transfer. A research team is currently studying red algae in Yellowstone Park in the United States and found that some red algae in the hot springs here have obtained genes from bacteria in the same area, and the differences in these genes are very small. If algae without this gene can be found in other hot springs in Yellowstone, it means that the process of horizontal gene transfer has not yet begun to occur, and they will have the opportunity to capture the process of gene transfer.
Perhaps the evolution of organisms is not as slow as Darwin suggested. When the naughty wind blows in the ecological environment, it will blow DNA all over the place, wandering between the branches of the tree of life, pushing the direction of different branches. The evolutionary models of modern science and the development of genetics will help us trace older gene transfer phenomena, and also give us a better understanding of where we came from and how to better coexist with our environment.
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