Modifications (genetics)

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The term modifications in genetics refers to both naturally occurring and engineered changes in DNA. Incidental, or natural mutations occur through errors during replication and repair, either spontaneously or due to environmental stressors. Intentional modifications are done in a laboratory for various purposes, developing hardier seeds and plants, and increasingly to treat human disease. The use of gene editing technology remains controversial.

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Genetic modifications (incidental and intentional)

Visualization of genetic modification with a piece of DNA being removed by tweezers. Genetic engineering logo.png
Visualization of genetic modification with a piece of DNA being removed by tweezers.

Modifications are changes in an individual's DNA due to incidental mutation or intentional genetic modification using various biotechnologies. [1] Although confusion exists between the terms "modification" and "mutation" as they are often used interchangeably, modification differentiates itself from mutation because it acts as an umbrella term, encompassing both definitions of mutation and genetic engineering. [1] Both of these subcategorizations result in a change affect an organism's obervable characteristics, also known as their phenotype,caused due to alterations in an organism's genotype, or their specific alleles, resulting in altered gene expression. [2] Although heritability plays a large role in an individual's expression, like in cases of epigenetic modifications, not all instances of modification are heritable. No matter the origins of such variation at the genetic level, it clearly impacts the creation and interaction of proteins, changing cell function, phenotype, and organism function. [3]

Types of modification

Genetic modifications can occur naturally, through aforementioned mutations in an organism's genome, or through biotechnological methods of selecting a gene of interest to manipulate in order to make something new or improve upon what already exists. [1] This distinction between changes that occur naturally and those that are intentional is key to understanding the difference between mutation and genetic engineering. [1]

Mutation (incidental)

Mutation can be more accurately defined as any non-combinatorial change in phenotype that is able to be consistently inherited from parent to offspring over generations. [1] Mutations can be attributed to many factors and come in numerous different forms, however they can mostly be attributed to mistakes that occur during DNA replication or exposure to external factors. [4] As cellular processes are highly efficient, they are not perfect causing disparities between organisms of the same species. [4] These disparities can cause many different phenotypic effects of all intensities, ranging from no observable impact at all to possible inviability. [4] Due to environmental conditions such as climate, diet, oxygen levels, light cycles, and mutagens or chemicals which are strongly related to disease susceptibility, genes expression can vary. [5] [6] The timing and duration of exposure to such elements is a critical factor as well as it can significantly impact the phenotypic response of an organism, generally increasing severity with time. [7]

Methods:

There are several methods, or forms, of mutation that exist including spontaneous mutation, errors during replication and repair, as well as mutation due to environmental effects. [8] These origins of mutations can cause many different types of mutations which influence gene expression on both large and small scales. [8]

Genetic engineering (intentional)

Genetic engineering is a type of intentional genetic modification, which uses biotechnology to alter an organism's genome.[ citation needed ] According to World Health Organization (WHO), genetically modified organisms are defined as "Organisms (i.e. plants, animals or microorganisms) in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or natural recombination”. [9] This type of modification can involve insertions or deletions of DNA bases into the existing genetic code. [10] In biotechnological methodology, a series of four steps are used in order to create a genetically modified organism (GMO). [11]

    1. Identify
      1. Researchers identify a trait of interest usually based on a desire to solve a problem. [11]
    2. Isolate
      1. Researchers the sequence of the specific trait by comparing genomes of organisms within the same species, with and without the trait. [11]
    3. Insert
      1. Next, they utilize the sequence(s) and various enzymes to insert the trait's genes into a plasmid vector, which can then be inserted into bacteria to propagate the preferable gene. [11]
    4. Grow
      1. A sign of the creation of a successful GMO is growth and replication with the newly edited genome with no detriments to the organism due to the new modification. [11]

Methods:

Image depicts the CRISPR genome editing proc DNA Repair-colourfriendly.png
Image depicts the CRISPR genome editing proc

CRISPR methods are a popularly used type of the aforementioned process of genome editing. [12] Standing for 'Clustered Regularly Interspaced Short Palindromic Repeats', CRISPR gene editing allows scientists to manually alter gene expression, correcting errors or creating new variations. [12] Since 2012, scientists have worked to develop this technology which has the opportunity to both cure genetic diseases and genetically modify traits to be most desirable, purposefully altering DNA with a high degree of precision. [13]

Examples

Mutation (incidental)

The dandelion: Most dandelions have long stems, but an increase in potential threats in their environment have caused average dandelion stem length to decrease within certain species, allowing them to better avoid said threats. [14] This adaptation was possible due to a mutation occurring in a shorter-stemmed individual being selected by environmental pressures. [15] Because the shorter-stemmed dandelions had higher fitness than long-stemmed dandelions and were able to survive more often, the genetic frequency of the population was altered, genetically modified through the original occurrence of a mutation. [15]

Sickle cell disease: In a healthy individual, the HBB gene is responsible for encoding hemoglobin which carries oxygen throughout the body. [16] However, when a person has this disease due to inheriting two mutated copies of the HBB gene due to a base pair point mutation, their red blood cells are shaped differently. [16] This altered shape results in blockages of blood flow with serious health implications. [16] On the other hand, those who inherit only one mutated copy of this gene have higher protection against malaria. [17]

Genetic engineering (intentional)

Alzheimer's disease: In a synthetic example in a laboratory, scientists isolated the amyloid precursor protein (APP) gene, known for using Alzheimer's in humans, and transmitted it into the nerve cells of worms. [10] In doing this, scientists aimed to study the progression of Alzheimer's disease in this simple organism by tagging the APP protein with green fluorescent protein which allowed them to better visualize the gene as the worm aged. [10] Using what they learned from experimentation with the simple worm and the APP gene, scientists increased their understanding of this gene's role in causing Alzheimer's disease in humans. [10]

Insulin: The first use of genetically modified bacteria was for the medical insulin that diabetics need to medically control their blood sugar. [18] Through the following steps, scientists are able to genetically engineer a medical product that millions of people rely on worldwide: [10]

  1. A small piece of DNA is extracted from a circular form of bacterial or yeast DNA called a plasmid. A scientist will extract this DNA through using specific restriction enzymes.
  2. Then, a scientist will insert the human gene for insulin into the gap left by the extracted DNA. This plasmid is now considered a genetically modified entity.
  3. The genetically modified entity is reintroduced into a new bacterial or yeast cell.
  4. This cell will then undergo mitosis and divide rapidly, producing insulin suitable for human needs.
  5. Scientists grow the genetically modified bacteria or yeast in large fermentation vessels, which contain all of their necessary nutrients, and allow large amounts of insulin to be cultivated.
  6. When fermentation is complete, the mixture is filtered to produce the final the insulin.
  7. The insulin is then purified and packaged into bottles and insulin pens for distribution to patients with diabetes.

Ethics of genetic engineering

Common products of genetic engineering Applications of combinatorial gene circuit optimization strategies.svg
Common products of genetic engineering

Fast-paced developments in the CRISPR-Cas9 gene editing technology has increased both the concerns and relevance of this ethical controversy as it has become more popularly used. [19] [20] The scientific community recommends continued evaluation of risks and benefits of utilizing genetically modified organisms in everyday life. [21] Genetic modifications are studied by researchers under controlled conditions after they are inserted into an organism, allowing for improved scientific understanding of the effects of certain gene modifications and certain organism responses.

Humans

In April 2015, gene editing technology was used on human embryos and debate about the ethics of such actions persisted since. [22] Nonetheless, scientists and policymakers are in agreement that public deliberations should decide the legality of germ line genome editing. [23] Modifying a person's non-heritable DNA with the goal of improving one's medical condition is generally accepted and has a plethora of ethical protocols monitoring such procedures. [19] This includes modifications like organ donation, bone marrow transplants, and types of gene therapies, all of which consider cultural and religious values. [19] On the other hand, there is contention surrounding heritable gene modification exemplified by the fact that 19 countries have outlawed this type of genetic modification. [19] For those who believe the vitility of a human embryo is equivalent to an adult, genome editing in early development occurring at or immediately following fertilization raises moral concerns. [13] In order to mitigate these concerns, studies using human embryos have used embryos from left over IVF treatments. [13] Scientists have also suggested creating fertilized zygotes from donated sperm and eggs strictly for research purposes. [13] However, this raises an additional ethical concern within the scientific community about the concept of a zygote being created only to be used for experimentation. [13]

Foods

Debate also surrounds genetically engineered food in terms of the controversial health and environmental effects that it may have in various time scales. [24] Regulations have been implemented for approval of genetically modified foods to reduce some uncertainty that remains in this field. [25] The reasons in favor of development of genetically modified foods include to meet the demands of the exponentially growing human population, to substitute for the decrease in farmable land, and to address the decrease in genetic diversity which limits possible improvement of species. [24] Additional benefits include improved herbicide tolerance, increased pest and bacterial/fungal/viral resistance, higher stress tolerance, and increased nutrient content within the organism. [26] The biotechnology of genetic engineering provides the opportunity to achieve global food security by addressing these problems and positively impacting the food production economy. [24] Potential health risks are also being researched and there are requirements for the safety of genetically modified foods to be clarified before they are consumed by the public. Environmental consequences are also considered due to disruptions within the food web when these organisms are added to a previously balanced ecosystem. [24] As genetic modification is so fast, the environment may not be able to adapt and integrate the new organism into the ecosystem or it could have unwanted effects on its surroundings. [26] Other impacts on the environment include unnatural gene flow, modification of soil and water chemistry, and reduction of species diversity. [25]

Future implications of modification

Ethical considerations regarding gene editing are largely controversial within the scientific community due to its open ended implications for the rest of society. [19] Although no consensus has been reached, there are plans in place to utilize the available resources to continue education, scientific research as well as research on ethical, legal, and social issues associated with genetic modification. [20]

Related Research Articles

<span class="mw-page-title-main">Biotechnology</span> Use of living systems and organisms to develop or make useful products

Biotechnology is a multidisciplinary field that involves the integration of natural sciences and engineering sciences in order to achieve the application of organisms and parts thereof for products and services.

<span class="mw-page-title-main">Genetically modified organism</span> Organisms whose genetic material has been altered using genetic engineering methods

A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified (GM), including animals, plants, and microorganisms.

<span class="mw-page-title-main">Genetic engineering</span> Manipulation of an organisms genome

Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms.

<span class="mw-page-title-main">Gene therapy</span> Medical technology

Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.

Gene knockouts are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs.

Agricultural biotechnology, also known as agritech, is an area of agricultural science involving the use of scientific tools and techniques, including genetic engineering, molecular markers, molecular diagnostics, vaccines, and tissue culture, to modify living organisms: plants, animals, and microorganisms. Crop biotechnology is one aspect of agricultural biotechnology which has been greatly developed upon in recent times. Desired trait are exported from a particular species of Crop to an entirely different species. These transgene crops possess desirable characteristics in terms of flavor, color of flowers, growth rate, size of harvested products and resistance to diseases and pests.

<span class="mw-page-title-main">Genetically modified food</span> Foods produced from organisms that have had changes introduced into their DNA

Genetically modified foods, also known as genetically engineered foods, or bioengineered foods are foods produced from organisms that have had changes introduced into their DNA using various methods of genetic engineering. Genetic engineering techniques allow for the introduction of new traits as well as greater control over traits when compared to previous methods, such as selective breeding and mutation breeding.

<span class="mw-page-title-main">Human genetic enhancement</span> Technologies to genetically improve human bodies

Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases, prevent the possibility of getting a particular disease, to improve athlete performance in sporting events, or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. These genetic enhancements may or may not be done in such a way that the change is heritable.

<span class="mw-page-title-main">Designer baby</span> Genetically modified human embryo

A designer baby is a baby whose genetic makeup has been selected or altered, often to exclude a particular gene or to remove genes associated with disease. This process usually involves analysing a wide range of human embryos to identify genes associated with particular diseases and characteristics, and selecting embryos that have the desired genetic makeup; a process known as preimplantation genetic diagnosis. Screening for single genes is commonly practiced, and polygenic screening is offered by a few companies. Other methods by which a baby's genetic information can be altered involve directly editing the genome before birth, which is not routinely performed and only one instance of this is known to have occurred as of 2019, where Chinese twins Lulu and Nana were edited as embryos, causing widespread criticism.

<span class="mw-page-title-main">Gene targeting</span> Genetic technique that uses homologous recombination to change an endogenous gene

Gene targeting is a biotechnological tool used to change the DNA sequence of an organism. It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change. Gene targeting relies on the presence of a repair template to introduce the user-defined edits to the DNA. The user will design the repair template to contain the desired edit, flanked by DNA sequence corresponding (homologous) to the region of DNA that the user wants to edit; hence the edit is targeted to a particular genomic region. In this way Gene Targeting is distinct from natural homology-directed repair, during which the ‘natural’ DNA repair template of the sister chromatid is used to repair broken DNA. The alteration of DNA sequence in an organism can be useful in both a research context – for example to understand the biological role of a gene – and in biotechnology, for example to alter the traits of an organism.

<span class="mw-page-title-main">Insert (molecular biology)</span>

In Molecular biology, an insert is a piece of DNA that is inserted into a larger DNA vector by a recombinant DNA technique, such as ligation or recombination. This allows it to be multiplied, selected, further manipulated or expressed in a host organism.

<span class="mw-page-title-main">Genetically modified animal</span> Animal that has been genetically modified

Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.

<span class="mw-page-title-main">Genome editing</span> Type of genetic engineering

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases, and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

<span class="mw-page-title-main">History of genetic engineering</span>

Genetic engineering is the science of manipulating genetic material of an organism. The first artificial genetic modification accomplished using biotechnology was transgenesis, the process of transferring genes from one organism to another, first accomplished by Herbert Boyer and Stanley Cohen in 1973. It was the result of a series of advancements in techniques that allowed the direct modification of the genome. Important advances included the discovery of restriction enzymes and DNA ligases, the ability to design plasmids and technologies like polymerase chain reaction and sequencing. Transformation of the DNA into a host organism was accomplished with the invention of biolistics, Agrobacterium-mediated recombination and microinjection. The first genetically modified animal was a mouse created in 1974 by Rudolf Jaenisch. In 1976 the technology was commercialised, with the advent of genetically modified bacteria that produced somatostatin, followed by insulin in 1978. In 1983 an antibiotic resistant gene was inserted into tobacco, leading to the first genetically engineered plant. Advances followed that allowed scientists to manipulate and add genes to a variety of different organisms and induce a range of different effects. Plants were first commercialized with virus resistant tobacco released in China in 1992. The first genetically modified food was the Flavr Savr tomato marketed in 1994. By 2010, 29 countries had planted commercialized biotech crops. In 2000 a paper published in Science introduced golden rice, the first food developed with increased nutrient value.

<span class="mw-page-title-main">Genetic engineering techniques</span> Methods used to change the DNA of organisms

Genetic engineering techniques allow the modification of animal and plant genomes. Techniques have been devised to insert, delete, and modify DNA at multiple levels, ranging from a specific base pair in a specific gene to entire genes. There are a number of steps that are followed before a genetically modified organism (GMO) is created. Genetic engineers must first choose what gene they wish to insert, modify, or delete. The gene must then be isolated and incorporated, along with other genetic elements, into a suitable vector. This vector is then used to insert the gene into the host genome, creating a transgenic or edited organism.

<span class="mw-page-title-main">Gene drive</span> Way to propagate genes throughout a population

A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring. Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species.

Biotechnology risk is a form of existential risk from biological sources, such as genetically engineered biological agents. The release of such high-consequence pathogens could be

Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. This is achieved by altering the genes of the germ cells, which then mature into genetically modified eggs and sperm. For safety, ethical, and social reasons, there is broad agreement among the scientific community and the public that germline editing for reproduction is a red line that should not be crossed at this point in time. There are differing public sentiments, however, on whether it may be performed in the future depending on whether the intent would be therapeutic or non-therapeutic.

<span class="mw-page-title-main">He Jiankui affair</span> 2018 scientific and bioethical controversy

The He Jiankui affair is a scientific and bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018. He became widely known on 26 November 2018 after he announced that he had created the first human genetically edited babies. He was listed in Time magazine's 100 most influential people of 2019. The affair led to ethical and legal controversies, resulting in the indictment of He and two of his collaborators, Zhang Renli and Qin Jinzhou. He eventually received widespread international condemnation.

<span class="mw-page-title-main">CRISPR gene editing</span> Gene editing method

CRISPR gene editing standing for "Clustered Regularly Interspaced Short Palindromic Repeats" is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.

References

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  15. 1 2 Entine, Jon. "GMOs, Yes!". Common Reader. Retrieved 2019-10-24.
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