Genome

Main article: Chromosome
Main article: Genetics
Main article: Artificial genome

2024

Recording on 5D crystal

In mid-September 2024, scientists at the University of Southampton recorded for the first time a complete human genome on a 5D memory crystal - a revolutionary data storage format that could last for billions of years.

The team hopes that crystals like this can become the basis for the revival of humanity even after extinction, if science allows it. The technology could also be used to build a robust database of genomes of endangered plant and animal species.

The human genome was first recorded on a 5D crystal

Unlike other storage formats that degrade over time, 5D memory crystals can store up to 360 terabytes of information without loss for billions of years, even at high temperatures. Since 2014, these crystals hold the Guinness World Record as the strongest data storage material.

A team of Southampton scientists used ultrafast lasers to accurately record data into nanostructured voids oriented inside silicon, with cell sizes up to 20 nanometers. Currently, it is not possible to create humans, plants and animals synthetically using only genetic information, but significant advances have been made in this direction in recent years, which gives hope for the use of 5D crystals in the future.

From the work of other researchers, we know that the genetic material of simple organisms can be synthesized and used in an existing cell to create a viable living sample in laboratory conditions, "said the main researcher, Professor Kazansky. - A 5D memory crystal opens up the possibility for other researchers to create an eternal repository of genomic information from which complex organisms, such as plants and animals, can be restored.[1]

A new genome editing technology has been mastered. It is more efficient and accurate than CRISPR

In early July 2024, an article was published by biologists from the University of Sydney, who presented a new genome editing technology more efficient and accurate than CRISPR. The unique DNA recombinase allows large segments of DNA to be inserted, removed, or inverted, using bridge RNA to precisely select the gene sequence.

The new tool uses IS110, a special type of transposon known as "jumping genes." The team of researchers found that transposons use a unique RNA-based navigation system. One end of the RNA attaches to the DNA segment intended to be inserted, and the other end binds to the DNA fragment at the insertion site in the genome. Such RNA acts as a bridge between two DNA segments. Thus, one RNA sequence identifies the target genes, similar to CRISPR, while the other finds a segment of DNA that needs to be altered. But unlike CRISPR, this system allows the addition, deletion or reversal of gene sequences of almost any length without the side effects associated with DNA breaks.

Scientists unveil new genome editing technology

The system controlled by "bridge" RNA already allows successful editing of genes in bacteria and in vitro, although the possibility of its application on human cells remains uncertain. If it can be adapted for humans, it could revolutionize genome editing through its compact size and ability to alter DNA sequences thousands of bases long, that is, entire gene complexes. At the same time, genome editing using bridge RNA avoids the formation of "scars," providing accurate control over manipulations with the genome. In addition, such technology will allow more accurate and large-scale changes in the genomes of plants and animals, increasing agricultural productivity.^[2]

The revolutionary MOBE gene editing system is presented. It will help treat diseases

Researchers at the University of California, San Diego, have unveiled an effective new MOBE genome editing tool that allows multiple point mutations to be corrected simultaneously. In the future, this may become the basis for the treatment and modeling of various polygenic diseases, including complex and rare ones. Read more here.

2023

The first Russian genomic printer has been created

In December 2023 Tomsk University of Control Systems and Radio Electronics (TUSUR) , they announced the creation of the first Russia genomic printer. We are talking about an oligonucleotide synthesizer, the press service of the university clarifies. More. here

'Markings' found in bacteria DNA

Scientists from NRNU MEPhI and the Federal Research Center of Biotechnology of the Russian Academy of Sciences have developed a mathematical algorithm that allows you to find repeating elements in genomes with high accuracy. They tested the new approach on nine species of bacteria, and previously unknown repeats were found in the genomes of each species, forming a kind of "marking" in the bacterial genome. According to the researchers, the algorithm will help find new genetic targets to increase the productivity of bacterial strains or to obtain new antibiotics. NRNU MEPhI announced this on September 25, 2023.

In the genomes of most multicellular organisms (from yeast to humans) there are repeating nucleotide sequences, where they are a kind of letters that make up DNA. Each such repeat has a length of several hundred nucleotides, and they are scattered throughout the genome, said Maria Korotkova, associate professor of the Department of Cybernetics at the Institute of Intelligent Cybernetic Systems, NRNU MEPhI.

According to her, to search the genomes of dispersed repeats, there are many mathematical algorithms that even allow you to detect "distorted" copies, that is, those repeats in which any mutations and sequences of which differ occurred.

However, such changes in the process of evolution can accumulate so many that it becomes impossible to find sequences not similar to each other in the genome, "Maria Korotkova explained.

To solve this problem, scientists are looking for new approaches to detect dispersed repeats "scattered" in the genomes of various organisms. Previously, such repeat families were encountered by researchers only in the genomes of multicellular organisms, while in the genomes of bacteria they were not known.

Scientists from NRNU MEPhI and the Federal Research Center "Fundamental Foundations of Biotechnology" have proposed a method for finding repeating sequences.

The principle of its operation can be compared with the search for a mathematical matrix consisting of columns and rows, which best describes the repeat family. The proposed algorithm is optimal for the accuracy of finding "scattered" repeats in the full genome, since it takes into account the possibility of nucleotide substitutions and their mutations, "said Evgeny Korotkov, professor at the Department of Applied Mathematics at NRNU MEPhI.

The authors applied the algorithm to find repeats in the genomes of nine bacterial species. They managed to identify for the first time in E. coli three families of repeats 400-600 nucleotide pairs long, which in total occupy almost 50% of the entire genome of the bacterium. Previously, similar elements of only shorter length - up to 300 nucleotide pairs - and in much smaller quantities were known from this microorganism.

In the genetic sequences of other bacteria, 1-2 families of equally large (400-600 nucleotide pairs) repeats were found.

We can say that there is a certain marking in the genomes of bacteria, similar to kilometer-long pillars on the road. The discovered code can serve as the basis for folding DNA into a nucleoid that largely determines the expression of bacterial genes. This opens up great opportunities to create new microorganisms useful for humans, "said Maria Korotkova.

The new approach, according to scientists, will help analyze not only bacterial genomes, but also the genetic sequences of multicellular organisms, for example, animals and plants. This will help to better understand the evolution of genomes and their individual elements, and, in the case of bacteria, find targets to create new antibiotics or increase the productivity of biotechnology-valuable strains.

Smartwatch instead of pills: gadgets will start programming your health on DNA code

In early June 2023, specialists from the Swiss Higher Technical School of Zurich (ETH Zurich) announced the development of an electrogenetic interface that makes it possible to control the activity of human genes through a special wearable device. The technology is called DART (DC-Activated Regulation Technology). Read more here.

How 3D genomics is already helping to understand how our genes work

On May 8, 2023, American scientists from the Massachusetts Institute of Technology (MIT) announced the development of a new technology that allows analyzing the 3D interaction of sections of the genome with unprecedented accuracy. The method is expected to shed light on the origin and progression of genetic diseases, as well as help in creating advanced treatments. Read more here.

The world's first database of all human genes and genetic variations has been created

health care USA On May 10, 2023, the National Institutes (NIH) reported that researchers had formed the world's first human pangen -- an extensive database of all genes and genetic variations that can manifest in humans.

The work was led by the international Consortium for the Study of the Human Pangenome, a group funded by the National Human Genome Research Institute (NHGRI) as part of the NIH. It is noted that the genomes of people coincide by about 99.6%. But the remaining 0.4% are responsible for millions of various signs and features - from eye color and growth to health and predisposition to certain diseases.

To better understand the variations, experts have created a "standard" human genome - a combination of genomic sequences of several people. The first variant, introduced in April 2003, covered about 92% of the genome. Another 8% remained hidden from scientists for a long time due to the lack of the necessary technologies for mapping. But over the years, advanced developments have filled the gaps.

The pangen presented is based on the genomes of 47 representatives of different ethnic and racial groups of people. Since each person carries a paired set of chromosomes, each with its own set of genetic information, the pangen ultimately includes 94 different sequences. Experts were able to separate the genetic information obtained from individual sets of chromosomes of the study participants. As part of the project, about 119 million base pairs and 1,115 gene duplications were added to the base. Thanks to the emergence of the pangenome, doctors will be able to speed up clinical research and deepen their understanding of the links between genes and the development of diseases. By mid-2024, scientists expect to increase the number of people whose genetic information is included in the pangen to 350 people.^[3]

Coronavirus causes changes in the structure of the genome

On March 23, 2023, the results of a study were released stating that the SARS-CoV-2 coronavirus infection, which provokes the COVID-19 disease, causes changes in the structure of the human genome. Read more here.

2022: Oncology managed to cure by applying a revolutionary method of DNA editing

In mid-December 2022 the British , doctors cured a 13-year-old girl named Alice from acute forms of leukemia with basic genome correction. The technology was invented six years ago, but was used for the first time.

Alice's cancer was discovered in the spring of 2021, the disease quickly progressed. When chemotherapy and bone marrow transplants didn't work, doctors embedded modified donor T lymphocytes, cells capable of killing tumors, into the girl's genome. All other treatments for Alice's leukemia were unsuccessful.

So doctors at Great Ormond Street Hospital used genome editing to accomplish the feat of biological engineering and create a new living drug for it. Six months later, the cancer has not been detected, but Alyssa is still being monitored in case he returns.

T-cells should be defenders of the body - to look for and destroy threats, but for Alice they became a danger and got out of control. Her cancer was aggressive. Chemotherapy and then a bone marrow transplant failed to rid her of her cancer. If not for the experimental drug, the only way out would be to just make Alyssa as comfortable as possible.

Base editing in the genome base allows scientists to increase the exact part of the genetic code and then change the molecular structure of only one base, converting it into another and changing genetic instructions. A large team of doctors and scientists used this tool to create a new type of T cell capable of tracking down and killing Alyssa's cancer T cells. They started with healthy donor-derived T cells and proceeded to modify them.

• The first basic modification disabled the T cell targeting mechanism to prevent them from attacking Alyssa's body.
• The second edit removed a chemical label called CD7, which is on all T cells.
• The third edit was an invisibility cloak that prevented cell death from the chemotherapeutic drug.

One month later, Alice went into remission, but she was once again transplanted with bone marrow to support immunity, and six months after editing the genome, cancer tests were negative.

Alice was the first of 10 children to undergo clinical trials. Scientists believe that this method will become a new industry in medicine and will make a breakthrough in the treatment of cancer. Since it allows you to force the immune system to kill cancer tumors.^[4]

2021: Creating genomic DNA that 'reproduces'

In late November 2021, Professor Norikazu Ichihashi and colleagues at the University of Tokyo successfully induced gene expression from DNA characteristic of all life for the first time and demonstrated evolution by continuous replication extracellularly using only cell-free materials such as nucleic acids and proteins. The ability to reproduce and evolve is one of the defining characteristics of living organisms.

However, until the end of October 2021, no artificial materials with such characteristics were created. In order to create an artificial molecular system capable of multiplying and evolving, information encoded into deoxyribonucleic acid (DNA) must be translated into ribonucleic acid (RNA), proteins must be expressed, and the DNA replication cycle with these proteins must continue in the system for a long time. Until now, it has not been possible to create a reaction system in which the genes necessary for DNA replication were expressed, and at the same time these genes would fulfill their function.

The group succeeded in translating genes into proteins and replicating the original circular DNA with the translated proteins using circular DNA carrying the two genes required for DNA and cell-free system replication. Moreover, the scientists also successfully perfected DNA by converting it into DNA with a 10-fold increase in replication efficiency, continuing this DNA replication cycle for about 60 days. By adding the genes needed for transcription and translation into artificial genomic DNA developed by the team of scientists, it will be possible over time to create artificial cells that can grow autonomously simply by feeding them small molecule compounds such as amino acids and nucleotides. In the event that such artificial cells can be created, it can be expected that useful substances, which are produced with the help of living organisms by November 2021, will become more stable and easily controlled.

This study was conducted under the guidance of Professor Norikazu Ichihashi, scientific director of the project for the development of a self-regenerating artificial genome replication-transcription-translation system. In this area of research, the group seeks to elucidate basic principles regarding the structure and function of genomes to create platform technology for the use of cells.^[5]

2019

All newborns in Britain will be given genome sequencing

In early November 2019, Minister health care Great Britain Matt Hancock announced that all British newborns would be given genome sequencing. More. here

The world's first living organism genome, fully generated on a computer

In early April 2019, the creation of the first genome of a living organism, fully generated on a computer, was announced. This achievement was noted by specialists from the Swiss Higher Technical School of Zurich. According to them, further improvement of the technology will allow obtaining completely artificial forms of biological life.

Scientists have developed a new method that greatly simplifies the production of large DNA molecules containing a huge number of genes. This method helped them build the first genome of the bacterium, fully computer-generated.

Experts worked with the genome of a harmless bacterium of the species Caulobacter crescentus, which contains four thousand genes. Such a bacterium can often be found in rivers and lakes around the world. In her honor, the genome was named Caulobacter ethensis-2.0. 

By early April 2019, the computer-generated genome is one large DNA molecule , not a living organism. However, tests showed that 580 of the 680 artificial genes turned out to be functional, the researchers noted.

This is due to the fact that  not only protein sequences are recorded in the bacterium genome, but also  regulatory regions and RNA molecules, for whose work the preservation of the correct conformation is very important. Apparently, not all of them were known in advance, and therefore underwent "optimization," which  broke them.

Thanks to the knowledge gained, we will be able to improve our algorithm and develop a fully functional version of genome 3.0. We believe that it will soon also be possible to produce functional bacterial cells with such a genome. In the future, this could lead to the emergence of synthetic microorganisms that can be created for specific purposes - for example, to synthesize vitamins and drugs, "said Beat Kristen, one of the authors of the study.[6]

2016: Population genomic studies of Eurasians and Australians

Large population genomic studies of Eurasians and Australians have been conducted, as well as a large genomic study of Paleolithic Europeans.

2015: Sequenced European genome with inclusions from Neanderthal genome

Sequenced the genome of a European with recent inclusions from the Neanderthal genome aged 37-42 thousand years; a genomic study of a large population of Bronze Age Europeans and Asians, as well as a large genomic study of ancient and modern Native Americans, Paleoeskimos and Inuit.

2014: Sequenced human genome of clovis culture

The human genome of the clovis culture was sequenced, age 12.6 thousand years; sequenced the genome from the Malta site, age 23 thousand years; sequenced the genome from Ust-Ishim, age 45 thousand years; Upper Paleolytic were sequenced 36-38 thousand years old.

2011-2012: Obtained by Australian Aboriginal genome and sequenced genomes of Neolithic Europeans

The first Australian Aboriginal genome sequenced from a 90-year-old hair bundle was obtained. In 2012, scientists sequenced the genomes of Neolithic Europeans.

2010: First ancient human genome deciphered

The first ancient human genome has been deciphered; drafts of the first Neanderthal genome and the first Denisovan genome were obtained; the project "1000 genomes" has started.

1970-2020: The start of the development of population genetics

The active development of population genetics began in the late 70s. XX century, but only in the most recent years have significant successes been achieved in the field of decoding the ancient and modern human genome. The public following this new information is most interested in comparing paleo-DNA data with information about the genetic features of modern representatives of a particular ethnic group.

What data on the human genome operate modern paleogenetics? We are talking about special markers - sequences in sets of nucleotides located on the three main components of the inherited human genome - 23 pairs of chromosomes located in the nucleus of the cell, as well as mitochondrial DNA (mtDNA). Twenty-two paired chromosomes (autosomes), two sex chromosomes X and Y, and human mtDNA contain together approximately 3.1 billion base pairs of nucleotide-organic compounds adenine (A) with thymine (T) and guanine (G) with cytosine (C).

Gradually, when transmitting information encoded in sequences of nucleotide chains, various mutations accumulate, which are fixed in DNA and inherited. A set of information with currently accumulated DNA mutations is called a haplotype, and groups of related haplotypes are called haplogroups. In this case, 22 autosomal chromosomes are formed from both parents, mtDNA is inherited only on the maternal line, although it is present in both men and women, and the Y chromosome is transmitted only from father to son.

Thus, an interesting tool falls into the hands of researchers that allows you to build genealogical chains and connect past generations with those now living on the maternal (mtDNA) AND paternal (Y-chromosome) line. A huge number of autosomal markers allow with a high degree of probability to reconstruct some features of the human appearance, for example, hair and iris color or skin pigmentation.

MtDNA analysis in modern and ancient populations has been carried out for a long time - since the 1990s. This is due both to the limited number of nucleotides behind the mtDNA included in the shell (16.5 thousand pairs), and to its stability and good preservation in paleoanthropological material. To date, an extensive amount of information has been accumulated on mtDNA of numerous peoples of the Earth, the common female ancestor of the entire modern population, mitochondrial Eva, who lived in Africa about 185 thousand years ago, has been calculated - a branched tree of human mtDNA haplogroups has been built. However, the use of mtDNA in paleogenetics to study ethnogenesis is complicated by the social practices of people - patrilocal forms of family relations that are characteristic of most modern communities and with a high degree of probability were widespread in antiquity. With this form of marriage, the genetic set followed on the paternal side remains in place or moves with the population, and mtDNA is actively mixed together with the arrival of women in this population from other populations. This feature, which leads to a large heterogeneity of the populations studied from the point of view of mtDNA and complicates the isolation of haplogroups characteristic of a particular population, has already been noted in the course of numerous studies of modern and ancient ethnic groups.

From this point of view, a much greater potential promises the study of the Y chromosome, the analysis of which entered the arsenal of evolutionary genetics only recently. This chromosome contains much more data - up to 60 million nucleotide pairs, and its inheritance exclusively along the male line allows for a spatial analysis of the spread of certain haplogroups and analyze the degree of their participation in the formation of a particular ethnic group more reasonably. ^[7]

Notes