Why was the human genome never completed? So far, no human genome has been read completely. Scientists expect to pass this milestone for the first time this year.

Why was the human genome never completed?

Before the end of 2023, you should be able to read the complete human genome, which will be the story of a person; It will also provide insight into who he is and where he came from, and his future. The complete human genome is probably not very fun at first glance and it will be very, very long. But the online publication of the complete human genome without any flaws will be a very important moment.

At this point you may feel like you’ve heard this before: the human genome was published years ago. Was it not done perfectly?

In fact, the human genome had never been completely read. The first draft of the human genome was published in 2001, and then in 2003, a group of scientists from the Human Genome Project announced that they had completed the work. This sequence, which was prepared by combining DNA fragments from different people, became the reference sequence with which the DNA of other humans can be compared.

Compiling the human genome by combining the genomic information of several individuals was the best that scientists could do at the time, but it had significant flaws and errors. Later versions of the human genome improved, but many problems remained. Only in the last few years has technology advanced enough to read the entire human genome without gaps and with minimal errors.

But all human genome sequences published so far have been hybrid, using DNA from multiple individuals. This year, the entire genome of a person (a man named Leon Pushkin) is going to be published for the first time. This complete and single human genome will be a monumental technical achievement. It’s only been 70 years since Rosalind Franklin’s black-and-white image revealed the double helix structure of DNA and revolutionized scientists’ understanding of how genetic information is stored. Today, we have the ability to read the entire genetic book that gives rise to the unique characteristics of a human being.

But the project’s geneticists say this is just the beginning. They want to sequence the genomes of people from around the world to create a true picture of the genetic diversity of the human species. They want to find out what the previously unsequenced parts of the DNA do. They also want to introduce whole-genome sequencing into clinics to help doctors diagnose and treat diseases.

In short, the human genome will never be complete, and we will never finish reading it.

The first human genome

The Human Genome Major Project (HGP) was one of the largest scientific projects at a cost of about $3 billion. The goal of this project, which began in 1990, was to read the entire DNA that the average human carries in his cells. The first draft of the sequence was published a little over a decade later. In 2001, at the same time, another version of the human genome was published by Celera Genomics.

The human genome came with many promises. With the help of the human genome, we understand what genes do, especially genes that play a role in diseases. This enables personalized medicine where we receive treatments tailored to our genetic makeup.

The complete human genome also provides insights into our evolutionary origins: how exactly are we different from our closest living relatives, chimpanzees, and bonobos?

Some of these promises have happened and some have not yet been fulfilled. Our knowledge of the function of many genes and their roles in diseases ranging from breast cancer to schizophrenia has increased. However, most diseases are affected by hundreds of genes, so we are still a long way from genomic medicine.

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A small number of inherited diseases are caused by a faulty gene, and the use of genetic screening to identify people at risk for rare diseases is largely limited to those at high risk.

Genetics has also changed our understanding of human evolution. For example, it has been shown that our ancestors interbred with other hominids such as Neanderthals.

Meanwhile, in the background of scientists’ efforts to provide a complete human genome, lies the unpleasant fact that the human genome has never been truly complete. While geneticists have been revising it since the first draft was published (last revised in February 2022), parts of the genome are still missing.

Repeated sequences

One of the problems is that parts of DNA are highly repetitive. In certain parts of the genome, the same sequences are repeated over and over, sometimes thousands of times.

Duplicated DNA often appears in similar parts of the genome. Our DNA is not stored as a long, continuous rope, but is divided into smaller pieces called chromosomes.

Chromosomes are X-shaped (except for the Y-shaped chromosome carried by males), and there are 23 pairs of them in human cells. Each of the chromosomes has duplicated DNA at the end of its four arms (telomeres) and at the central junction (centromeres), and both of these are important.

Telomeres act as protective caps and their damage is associated with aging. Meanwhile, centromeres are important for the process of cell division that underlies growth and reproduction. DNA rearrangements at centromeres play a role in the development of some cancers.

The Human Genome Project failed to sequence the duplicated DNA and did not attempt to do so. Their method could not solve this challenge. They didn’t read the entire genome at once, but instead divided it into small pieces a few hundred bases long, read them, and then put the sequences together using a computer. This method is not efficient for repeated segments, because the computer does not know in what order those segments are put together. “Eight percent of the copy that was officially completed in 2003 was missing,” says Adam Filippi, head of the genome informatics division at the National Human Genome Research Institute in Maryland.

Therefore, our duplicated DNA remained almost completely unread for 20 years. Then in 2021, Filippi and his colleagues announced that they had all read it.

What is the genome?

The genome is often compared to a book written in the DNA alphabet instead of the English alphabet. The DNA alphabet consists of only four letters: A, C, G, and T. Each of these letters represents different molecules called “bases” that are strung along the length of the DNA molecule. Any particular sequence of these letters constitutes a gene. The responsibility of translating this information lies with the molecular machines inside our cells. Some genes provide the information needed to make different proteins that have different functions in the body, while other parts of DNA have regulatory functions. What the Human Genome Project team achieved was the exact order of bases along the length of DNA; Something like CGATTTCCGAAAA and so on for over three billion characters.

Reading the human genome from beginning to end

The Telomere to Telomere (T2T) Consortium was not a big, famous, multi-billion dollar project. “It was really a public effort that took place during birth,” says Karen Miga, a geneticist at the University of California, Santa Cruz. In the eyes of many genomic experts, we appeared out of nowhere.

” A key advance was the ability to accurately read long stretches of DNA, says Evan Eichler, a professor of genome sciences at the University of Washington in Seattle. Previously, technologies capable of reading long sequences had been developed, but until recently they were not accurate enough. Therefore, improving the accuracy of these technologies was a key development. Also, the ability to read sequences that spanned over 100,000 bases was an important advance.

T2T’s first major breakthrough came in July 2020 when the project’s researchers published the complete sequence of the X chromosome. At the time, the best available sequence of the X chromosome had 29 gaps, and the T2T team filled in all the gaps. The following year, they published the complete sequence of chromosome 8. In 2021, they also published a preprint titled “The Complete Sequence of a Human Genome,” in which they filled in 8 percent of the missing sequence.

Reading repetitions

But the human genome had not been read completely yet. Ishler says the team used a little trick that some called cheating.

Most cells in our body have two copies of each chromosome: one from the mother and one from the father. This makes it more difficult to put the sequences together on the computer because the two versions differ very little. To solve this problem, T2T used abnormal cells that have two copies of the father’s DNA that are nearly identical. The mentioned cells were the result of a hydatiform mole (molar or baby-eating pregnancy), which is a type of failed pregnancy.

Eggs and sperm have only one copy of each chromosome, so when a sperm fertilizes an egg, the resulting embryo has two copies. However, sometimes the egg loses its DNA and is then fertilized. Then the egg cell, which has lost its DNA, replicates the sperm’s DNA. Hydatidiform moles form dangerous lesions that look somewhat like cancer and must be removed. This is what T2T sequenced. According to some researchers, they had read only half of the genome, because the complete genome has two copies of any particular sequence. Although overall, their sequence was a clear improvement over previous sequences and added more than 200 million letters and two thousand genes to the human genome.

Having a complete genome means finally being able to understand what the repetitive segments of DNA do, Miga says. “Now that we have these maps, I’m very excited to see what sequences are in these regions,” he says. But what is their main function? And if there is a problem in these areas, how can it contribute to our understanding of human disease and human health?”

Repetitive DNA contains many sequences that can move around the genome and are called “mobile DNA”. “Many of these elements have played a role in our recent evolution,” says Rachel O’Neill, a molecular geneticist at the University of Connecticut in Storrs. “Many evolutionary mutations, including placentation, loss of the tail, and some brain functions, can be attributed to this type of driver DNA.”

Meanwhile, Eishler refers to duplications, where long stretches of DNA that can contain multiple genes are duplicated at once. These sequences can evolve at an extraordinary rate. Ishler says: “The result of this phenomenon is the emergence of new genes that are specific to humans. “These genes contribute disproportionately to the differences that make us human.”

While the human and chimpanzee genomes are 99% identical, duplications are one of the ways in which important differences can arise between us and chimpanzees. The originally published human genome was largely devoid of these duplicated sequences.

Neuroscientists have shown that some duplicated genes are important in brain function. But geneticists couldn’t study them precisely because they were in repeats that didn’t occur in older genomes.

The T2T sequence was finally published in a special issue of the journal Science in March 2022. But at that time the team was moving forward.

The remaining large gap was the Y chromosome, which is only present in males. Sperm usually carry only one sex chromosome (either an X chromosome or a Y chromosome). Because the hydatidiform mole DNA used by T2T came from sperm that contained an X chromosome, the Y chromosome was not sequenced. The team needed a male donor to finish their work, so they used Pushkin.

DNA donor

Pushkin is a systems biologist at Harvard Medical School in Boston, Massachusetts. Much of his research focuses on understanding the mechanisms of aging and how to slow them down. He believes that the human life span has no limit and can be increased. Genomics is a big part of his work. Pushkin has donated his DNA to a number of major sequencing projects.

Pushkin’s first donation was to the Personal Genome project, which was launched in 2015. The goal of the project was to attract volunteers who were willing to share their DNA publicly to enable faster and more efficient research, as well as to overcome fears about the potential misuse of genomic data.

A decade later, Pushkin’s DNA was again used by the GIAB project. The goal of the project was to sequence the genomes of cell lines that could be grown indefinitely in the laboratory and make it easier to study the effects of mutations. Pushkin’s genome was favorable because he had also enrolled his parents in the project and provided them with information on his mother, father, and son.

Pushkin does not regret his choices, although he points to an unpleasant consequence. “I can’t go to labs that work with my cells, because if my immortal cells somehow get into my body, my immune system won’t recognize them, and there’s a chance that the immune system will go into overdrive, and it’s a dangerous situation,” he says. come.” He is delighted to have his DNA sequenced again by T2T, this time in full.

In December 2022, T2T published another preprint paper describing the complete sequence of Pushkin’s Y chromosome. Since this chromosome has many repetitions and complications, more than half of the chromosome was not present in the past genomes. The new sequence added more than 30 million characters including dozens of genes.

The team is now working on Pushkin’s complete genome, including both copies of each chromosome. “We’ve finished sequencing and reconstructing it,” says Filippi. The resulting genome is complete and without defects and takes duplications into account. All that remains is the review. Filippi says there are a handful of errors we can check. He says their final genome should be published this year.

Pan Genome

Will the human genome be completed this year? The answer is no because there is no single human genome. Each person’s DNA is different and these differences are important. We won’t really understand the genome unless we have a record of how it differs between different populations.

The initial HGP project attempted to address this problem by drawing its sample from a few individuals, all from New York. The sequence that was released was a combination of all of them. Indeed, they tried to provide an average genome, but an American city cannot represent the full spectrum of human genetic diversity. This is why many members of the T2T Consortium are also enrolled in another project: the Human Pangenome Reference Consortium. The goal of this project is to sequence the genomes of hundreds of people from all over the world.

The project’s genomes will not be complete, as they will lose some degree of completeness in exchange for using automated methods that allow them to include more people in the study. In July 2022 the team published a preprint describing the 47 sequenced genomes that they had combined to create a draft “pangenome.”

They are now collaborating with researchers from around the world. “We don’t want this to be done exclusively in one place,” says Ishler. I think it is better to have genomes, especially from populations whose genetic diversity we have not identified well, and to do this in their own communities and by their own people.”

Pangenome’s effort has already paid off. Filippi is a co-author of a study published in January that identified a mechanism for a genetic abnormality. About 1 in 1,000 babies have a Robertsonian translocation, in which two chromosomes fuse together. If the genetic material is not destroyed, the health of the person is not affected, but in some cases, it can lead to conditions such as Down syndrome.

There appears to be a conserved sequence of DNA (that is, a sequence that is the same across species) that is found on multiple chromosomes. This can confuse the cellular mechanisms of DNA replication and cause chromosomes to fuse together. The critical sequence is located in a region that is both repetitive and highly variable between individuals, so it cannot be studied without multiple complete genomes.

Such findings explain why many project researchers want whole genome sequencing to be done in hospitals as well. “My ultimate goal is to be able to replicate T2T genomes in the clinic for any disease,” says Filippi. The methodology we have developed is in this direction. The cost of genome sequencing has fallen dramatically over the decades, so much so that the cost of the T2T project was much less than the cost of the original HGP.

Clearly, there is still much to learn from our genome. As new techniques reveal more secrets of the genome and make it possible to sequence more genomes, there is no end in sight. “As long as humans exist, the Human Genome Project will continue,” says O’Neill.

Why did the dinosaurs become extinct? Until now, some hypotheses have been presented regarding the cause of the extinction of dinosaurs. However, scientists have made a new discovery.

Why did the dinosaurs become extinct? But the generation of birds continued?

New research has discovered the reason for the mass extinction of dinosaurs at the end of the Cretaceous period. The reason for this problem was the long presence of the dinosaur embryo in the egg.

According to the article published in the journal PNAS, the dinosaur embryo was inside the egg for six months, which is twice as long as the longest duration of a bird embryo in the egg. Previously, dinosaur embryos were thought to last as long as bird embryos. If it turns out, this assumption is not valid.

The teeth of a fossilized fetus

Dinosaurs are actually more like reptiles with a longer embryonic period in eggs. Scientists have recently found out how long this animal species was in the egg by observing the traces of the teeth of a fossilized dinosaur embryo.

It is thought that the formation of dinosaur teeth is similar to other reptiles and mammals and their enamel and ivory layers are formed in a daily process; In this way, each line on the tooth, like the rings of a tree, determines the life span of a dinosaur. Paleontologists have been able to estimate the age of dinosaurs by using the method of orthodontic science that determines the number of human ages.

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“These lines on the dinosaur’s teeth are very distinct and noticeable,” said study author Gregory Erickson of Florida State University. The late arrival that led to extinction!

The long duration of the presence of dinosaur embryos in the egg caused this animal to become extinct at the end of the Cretaceous period.

Erickson says: When you look at sudden developments like this, it’s a warning that the planet’s resources are limited. Besides, the dinosaurs played bad cards in their survival game.

Dinosaurs’ large size, long time to reach sexual maturity, and their possible warm-bloodedness were reasons why they wasted so much energy. When the dinosaurs’ birth process was prolonged, more agile and stronger species emerged and came into play.

He added: After this extinction, the animals whose offspring were born more quickly began to fill the voids of the existing ecosystem. In fact, amphibians, lizards, and other small, cold-blooded animals that didn’t need much energy to reproduce survived. On the other hand, mammals and birds, which were inherently smaller than dinosaurs, reproduced at a faster rate.

What is mazut ? Mazut is an inseparable friend of air pollution and we hear its name a lot these days. Now, what exactly is this infamous fuel and what are its dangers for humans and the environment?

What is mazut and what are its disadvantages for humans and the environment?

With the arrival of the cold season, the issue of air pollution in big cities becomes one of the hot topics in every community. The main culprit of this problem is nothing but a fuel called “mazut”. To have a better understanding of this issue and to get to know the dimensions of this serious crisis, it is better to take a close look at this fuel and its complications.

What is mazut ?

The crude oil that is extracted from the ground has different compositions and must be refined using special methods. In the stages of refining crude oil by distillation, compounds called fuel oil are removed from the distillation tower. Mazut is one of the types of fuel oil, which, in addition to its very unfavorable quality, also has a very high viscosity.

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The necessity of using fuel oil in different fields is to convert this product into suitable petrochemical products. Such a change is made with the help of equipment that did not exist in the past. The same issue also made mazut used as a household fuel in countries like the former Soviet Union before being converted into other products.

This type of fuel oil also has a lot of sulfur in its composition, which must be removed before using it for various purposes. Fuel oil desulfurization is done in three ways:

• Wet method
• dry method
• Semi-dry method

Among the mentioned methods, the wet method is the most common method used for fuel oil desulfurization. In this method, with the help of adsorbents based on seawater, sodium, calcium, ammonia, potassium, and magnesium, the sulfur in fuel oil is extracted. Wet desulfurization, which consists of several successive stages, takes place in tanks called “wet washing towers”. What are the types of fuel oil?

The difference in the viscosity of diesel fuel causes this fuel to be divided into several different categories:

• CST180
• CST230
• CST280
• CST380
• M100

Meanwhile, fuel oil 100 (M100) is also divided into 4 different types due to the presence of different amounts of sulfur:

• High Sulfur: Contains 2 to 3.5% sulfur
• Normal Sulfur: Contains 1 to 2 percent of sulfur
• Low Sulfur: Contains 0.5 to 1 percent of sulfur
• Very Low Sulfur: Contains 0.5% sulfur

What is the use of mazut?

In addition to having a high burning heat, diesel fuel has a cheap price, which makes it suitable for use in thermal power plants, steam boilers, and ship fuel. It should be mentioned that European and American countries use it in different ways by breaking down the compounds of this fuel and producing diesel.

What are the effects of mazut on human health?

Burning fuel oil leads to the release of toxic sulfur dioxide gas (SO2), whose large amounts pose serious risks to human health. The standard amount of sulfur dioxide in the air is 10 ppb, and if the air we breathe contains more SO2, we will experience many problems.

A burning sensation in the nose and throat, breathing problems, chest pain, increased risk of heart disease and red eyes are among the symptoms that we will encounter if we are exposed to a small concentration of dioxygen.

The emission of bad smells in the air means increasing the amount of SO2 to more than 500 ppb. In such conditions, the concentration of this gas is at a lethal level and is considered a very serious risk to human health. In such a situation, air pollution and solutions to deal with it become the most important issue of society and attract the attention of experts and officials more and more.

Using the best air pollution monitoring programs and knowing the concentration of existing pollutants is one the important measures that can be taken in this situation. If the amount of atmospheric pollutants increases, it is better not to leave the house and if forced to leave the house, use suitable face masks.

What are the effects of mazut entering the environment?

In addition to the direct effect on human health, fuel oil affects our lives indirectly through the environment. One of the important and familiar effects of mazut entering the environment is the phenomenon of “acid rain”. The dissolution of heavy metals in the soil is considered the most important consequence of acid rain and leads to the phenomenon of soil erosion. This phenomenon causes the soil to lose its power to maintain the roots of trees and plants. In this situation, the vegetation will be lost and this will increase the possibility of flooding.

Soil and vegetation damage is a very important issue that seriously affects the future of mankind, But the point that makes this issue much more serious and worrying is the long-lasting nature of these complications. Research shows that compounds such as xylene and benzene, which enter the soil as a result of fuel oil breakdown, remain in the environment for more than 10 years.