All organisms and viruses are controlled by their genomes, in conjunction with their environment. Genomes are lists of instructions.
Every virus and organism has at least one copy of its genome in its body.
A change to the content of a genome is called a genetic modification. When it occurs, it usually produces some change to the body or the system of its organism or virus.
Every step in every evolutionary biological process on Earth is the result of a modification of a genome.
The operations of genomes and the environment cause everything that we do, and what happens to us. They also cause our emotional attitudes to all of our experiences.
In this lecture, I will discuss the following issues:
Relevant Aspects of Viruses and Organisms;
Structures and Components of Genomes;
The Processes of Genomes; and
Natural and Purposeful Genetic Modifications.
Viruses and Organisms
A virus is a closed shell containing a genome. Viruses are not organisms.
Organisms are of two kinds, prokaryotes, and eukaryotes.
The Prokaryotes are the Bacteria and Archaeons. Archaeons are similar to bacteria in size and structure, but have differences in their chemistry.
Prokaryotes are single cells. They have an enclosing cover, a genome, and internal and external organs. Their average size is about one hundred times that of viruses. But they are still very tiny. You need a powerful microscope to see them.
Eukaryotes are of four kinds, animals, plants, funguses, and protists. Animals, plants, and funguses each have their own common ancestor. Protists have a range of ancestries, all different from the other three.
Eukaryotes are much larger and more complex than prokaryotes.
The relevant genetic aspects of viruses and organisms are:
the natures of the of the cells of their bodies;
the processes of reproduction ; and
adaptation and evolution.
There are three kinds of cells, those of viruses, those of prokaryotes, and those of eukaryotes.
As I said earlier, viruses are closed cells made of proteins and containing a genome. Their genomes are instructions for replicating themselves.
Viruses cannot perform any actions. Their environment just pushes them around.
Prokaryotes are single cells containing a genome, and organs by which they can take in and ingest food, and move, and perform other actions.
Eukaryote cells are much larger and more complex than the cells of viruses and prokaryotes. Eukaryotes may be single cells, or multicellular, that is, consist of more than one cell. Their cells contain a nucleus, which is similar to the body of a prokaryote, and it contains the organism’s genome. The cell also contains organelles, which are tiny organs, that are essential for the functioning of the cell and of the whole organism.
Some of the organelles in the cell have their own genome, such as the mitochondria which are used for several of the functions of that cell.
Cells of all organisms contain a system for building a new cell, or a new organism, or a new virus. This system is similar to 3D printing.
Multicellular eukaryotes continually produce new internal cells for building the organism’s body and for replacing cells that are no longer functional. Also, they have sexual reproduction cells, which have some differences from the other cells.
Reproduction is the process of parts of the body of an organism acting together to produce offspring that will grow into an organism resembling its parent.
Viruses do not reproduce. When their DNA/RNA gets into a cell of an organism, they are replicated inside that cell, using the cell’s reproductive processes in accordance with whatever DNA/RNA gets into the cell.
Prokaryotes, being just one cell, reproduce by building a new cell inside their body and then splitting, or by producing buds on the outside of their bodies. The buds will then break off and grow to their full size. These kinds of reproduction are asexual, that is, not sexual. Some eukaryotes reproduce asexually, similarly to prokaryotes.
Sexual reproduction is a process in which more than one organism contributes a special part of its body material. This means that the newborn organism gets genes from both parents.
Most multicellular organisms start as one cell. Their cells continually reproduce until the organism has reached its full size. However, some funguses have no internal limit to their size. Some plants and animals can reproduce from parts that have been taken from their body.
All of the cells of a multicellular organism contain the same genome. But each kind of cell has its own function, and structure, and size, and material. This requires each kind of cell to employ only its own specific range of instructions. So each kind of cell has only its specific parts of its genome switched on.
There are molecules attached to the genome of each cell that determine which genes are switched on. They are the epigenome. The cells that produce sexual reproduction are arranged slightly differently from the others.
Changes to the epigenome are sometimes continued for a few generations.
Adaptation and Evolution
Adaptation means becoming more able to fit in with the environment. Adaptation is the result of advantageous changes to genomes and epigenomes. Those organisms that fitted better to their environment are more able to produce more offspring. Adaptation is a relatively short process, and more related to individual organisms. If it produces major structural change, this may lead to evolution.
Evolution is a longer process, with larger groups of close relationships that are subject to survival of the fittest.
One factor of the speed of modification, and hence of adaptation, is the life span of the organism. Some microorganisms have very short life spans, such as a few hours or less, which means that the next generation is ready to reproduce very quickly. This, in conjunction with continual errors, can produce very rapid mutations.
The processes of natural adaptation and evolution are not planned. They are caused by the environment, acting under all the forces and functions of nature, including genetic. The precise outcome is usually unpredicted. For example, it is influenced by which organisms mate with which.
Structure and Components of Genomes
Genomes are constructed as strings. They may be single strands, or two or more strands twisted together. RNA is a single strand. DNA consists of two strands, twisted and joined together. The genomes of most viruses and prokaryotes are DNA, but some are RNA.
The genomes of most viruses and prokaryotes are in the shape of a long, tangled, closed loop.
Eukaryotes, which are much larger organisms and have much larger cells, have much longer strings.
These strings are made of complex molecules connected end to end. One kind of molecule is the nucleotide. This comprises a kind of sugar attached to a nitrogenous base. (A base is the chemical opposite to an acid.) The human genome uses four slightly different bases. They are thymine, cytosine, guanine, and adenine, and are usually referred to by their initials, T, C, G, and A.
Each nucleotide has one base.
Nucleotides comprise the “letters” and then the “words” of the data in the genes. They also have other functions.
Our genomes have about 3.42 billion nucleotides.
Genomes operate in a way a bit similar to the cassettes of tape that were used for storing and presenting audio and video, before electronic digital systems were introduced.
The parts of the long strings of DNA, when they are not being used, are coiled tightly around spool-shaped proteins, so that they will fit inside the cell along with everything else.
These strings of DNA contain the genes that determine how the body and the mind work. The genes are organised into chromosomes, each chromosome containing the genes for its specific purposes.
These genes are the “words” representing the details of the specific instructions for each function of the gene. For example, sex chromosomes have genes that code for the organs and functions of sex cells.
The ends of each word and of each chromosome are indicated by short sequences of “letters”.
The genomes of most viruses have no chromosomes. A few prokaryotes have a few to several chromosomes. Many eukaryotes have a very large number of chromosomes.
In human genomes, there are 22 pairs of chromosomes to code for all of the bodily functions, plus one pair of sex chromosomes. Typically, but not always, the human female genome has two X chromosomes, and the male genome has one X chromosome and one Y chromosome. X and Y each have different genes.
Very occasionally, a baby is born with additional or different sexual chromosomes in its genome, such as two X chromosomes plus one Y chromosome. Having unusual sexual chromosomes affects the kind of body structure and identity of the person.
In eukaryote genomes, these genes are only a very small part of the total.
There is also a lot of other DNA, in addition to these chromosomes. This consists of accumulations of sections of DNA that get moved to different positions in the genome, or from DNA that has got in from the genomes of viruses and organisms. The movements are determined by the conditions of the genome and the body generally, and the nature of the sections being moved.
Most of these regions contain multiple copies of such sequences. This is what makes the total genome so much larger.
This additional genetic material was initially referred to as “junk DNA, but it is a lot more than that. Just as random interruptions sometimes lead to adaptation and evolution, so do the changes related to this other DNA.
The Processes of Reading Genomes
For genes to be activated, the relevant part of the DNA/RNA has to be presented to the processing part of the cell. This requires identifying the relevant part of the long string of DNA, and uncoiling it, and then recoiling the uncoiled section that has been used.
During this process, the two strands of that part of the DNA are separated. Through a series of copying from one of the strands, and including messenger RNA (mRNA), and enzymes, a new strand is produced that finally directs what has to be done.
When each detail is transferred, its strands reunite again, and are recoiled back into place.
The necessary processes for all this are controlled by the systems that were built into the cell when the cell was built using these processes.
The process is a bit simpler when the organism’s genome is only RNA.
How Genomes Get altered
Some modifications are routine processes. There are other causes of genetic modification. These are:
Errors in routine actions;
Environmental conditions; and
Errors in routine actions
Errors in routine actions are the result of something affecting a process that usually runs well.
This is exposure to high temperature, electromagnetic radiation such as X-rays and radioactivity, physical impact, and chemical action. These can disrupt the processes of the affected part of the organism.
Or it could be from viruses and bacteria getting into the blood of victims of aggressive organisms, great and small, and then getting from the blood into the genome.
Another cause is various kinds of microscopic strings of DNA or RNA, and/or with proteins, that are floating around. They can, along with viruses, land right into organisms, and into the organisms’ genomes and epigenomes.
Changes in the epigenome, are mainly caused by some stressful condition, such as high or low temperatures, or malnutrition, or low atmospheric oxygen concentration. It may be a temporary adaptation, or be continued through successive generations. If changes in the genome or epigenome affect the organism’s reproductive genes, the descendants of that organism will be affected.
Another kind of environmental modification occurs at the microscopic scale. Some bacteria, archaeons and other microorganisms sometimes donate and receive some of their genetic material, and/or pick up, and incorporate bits of stray DNA or RNA to add to their genomes.
In most of these cases, only a small amount of genetic material is added or subtracted, and it has a random effect on the recipient organism.
During the replication of viruses, mutations often occur when stray DNA or RNA gets into the infected cell. This adds to the genome of the infecting virus and to the consequent replications. This causes most of the evolution of new strains and species of viruses.
Sexual reproduction of organisms is the process of uniting a male and a female sex cell of the same, or very closely related, species. The strands of the sex cells split to produce four strands. One strand from each parent is sent to the ovum and the sperm, which then unite into a fertilised cell. This gives the descendants new genomes from their parents.
Mammal siblings have incidentally different genomes from each other, except for identical twins, whose genomes both came from the same fertilised egg, which had been split into two identical eggs. But on rare occasions, a mutation occurs in one of the twins early in the process, which makes the twins slightly different.
Other differences between siblings also occur during reproduction. When, in the recombination, the four strands of parental genes are reduced to the two strings of the child, the genes will be donated from only one of each strand.
If we were to call the strands from the woman F1 and F2, and the strands from the man M1 and M2, the combinations could be F1 and M1, F1 and M2, F2 and M1 and F2 and M2. Any of these could occur in the recombination. In this process, there is also no plan of the sequences in which the transferred chromosomes are arranged.
Sexual change can occur in some species of adult social animals, such as bees and some kinds of fish, When there is a shortage of females, and less often, shortage of males, some members of the group will change sex to improve the balance. This is likely to be a change of epigenomes, where different sexual genes are switched on and off.
Natural modifications range widely in kind and size, from as small as change of one “letter” or “word”, to long whole sections of DNA, being duplicated, removed, or altered.
One incorrect letter may sometimes cause a significant change in the functions of the organism, and a change of whole sections of DNA may sometimes have no effect.
When a cell’s genome is changed, or had an error in its production, that change may cause proliferations of the error and become a cancer.
Modifications can be in any part of a genome, including the epigenome.
The process of “survival of the fittest” may decide which changes in subsequent generations will survive and diversify, and which will not. Only time will tell how small or great each effect will be.
What I have been discussing so far, was all about natural modification. A small proportion of modification is purposeful. Purposeful changes to genomes are made by the selected use, by humans, in various ways. These are, using the workings of both nature and humans together making purposeful changes directly to the genome. A very tiny proportion is made by direct changes to the genome.
Purposeful modification is performed for a range of objectives, and it is conducted in various ways.
Objectives of Purposeful Genetic Modification
The objectives of purposeful modification are to:
Enable organisms to produce specific substances that could not otherwise be produced, and to produce significantly greater amounts of various substances;
Improve the yield and quality of various organisms;
Treat congenital defects, mainly in humans;
Help the treatment of some cancers;
Make organisms sterile;
Act as antibiotics;
Develop suitable organ transplants for humans, using organs of other mammals;
and to Produce vaccines.
Producing specific substances
Many kinds of organisms can be modified to produce substances on a large scale, by transferring DNA to them from other species that can produce it at a much larger and/or faster rate. The DNA is usually taken from multicellular organisms with long life cycles, and transferred to bacteria. Bacteria have very short life cycles, and so produce the relevant product at a much greater speed.
Improving the useful qualities of organisms
This is to make organisms of all kinds be more useful to us. Examples are:
Making fruits, etc., larger, or smaller, or more nutritious, more beautiful, more tasty, and spectacular, and no longer being poisonous or affecting people with allergies;
Making animals, etc., more helpful and safe for us, such as in turning savage wolves into obedient dogs, and in doing the hard work, as in horses, etc., and making animals better as food.
Treating congenital defects
Congenital defects can occur in us and other mammals, by modifications of their genome before or during the reproductive process. In some cases, it is now possible to identify and treat the relevant DNA and/or material.
Helping the treatment of some cancers
The DNA of some cancer cells can sometimes be modified so as to prevent the other cancer cells from reproducing.
Acting as antibiotics
Some kinds of bacteria that are resistant to antibiotics can be treated by changing the genomes of some of these bacteria in a way that stops the others from proliferating. I don’t know anything about how this is achieved.
Making organisms sterile
Making organisms sterile has two purposes.
One purpose is to reduce or eliminate pests such as mosquitoes and feral animals. This is done by producing a large number of sterile males and putting them into the environment.
The other purpose is to produce crops that can be reproduced only by seeds held by the people who have “invented” a particular strain that produces a new and valuable sterile crop.
The inventors get their income from the sale of seeds, and the farmers who buy the seeds get their income from the sale of the crops.
Making other organisms’ organs suitable to be transplants to humans
Scientists are learning how to modify donor organs from pigs and other organisms so that they are fully accepted by the human recipients immune system. This requires editing of both the donors’ and recipients’ genomes.
(Presumably, other parts of the donor animal could then be used, such as for human consumption.)
Some people regard this to be cruel. But we already treat animals in much more cruel ways.
Scientists are learning to use artificial intelligence to analyse some viruses to see what measures are needed to include in designing vaccines and reinforcing the immune systems of patients. This involves using genetic material, including gene editing. It is still in its early days.
Processes of Purposeful Genetic Modification
The processes of purposeful modification are;
Selective breeding and hybridisation, and
Over many past millenniums, people have been purposefully modifying the genomes of animals and plants, using selective breeding and hybridisation. They have done this to create new strains of animals and plants to suit particular uses.
Examples are the domestication of wolves to create dogs, and to improve animals such as cattle and hens, which produce food such as milk and eggs, and also become food, for humans. There is also the development of fruit and grain seeds from wild plants.
Selective breeding is choosing and breeding from individual organisms that seem to have better attributes than other specimens of the particular species, and also, selecting for specific attributes, such as for the different kinds of horses.
Inbreeding is mating very close relatives of the same species. Over successive generations, it produces both desired and undesired attributes.
Hybridisation is sexual mating of organisms of different but compatible species. It, also, occurs naturally.
Most hybrids can continually reproduce. When there is successive hybridisation, a huge range of very different strains can be produced. This is seen most often with purposefully modulated plants, particularly of decorative flowers..
Some kinds of hybrids are unable to reproduce, which means that it is a one-generation modification. Examples are mules, and some cats.
The liger, the product of a male tiger and a female lion, is the largest member of the cat family, and it is sterile. But many other hybrid cat species are successively fertile.
Purposeful hybridisation occurs in all of the kingdoms of eukaryotes, but less so with funguses.
Gene editing is the process of adding and/or removing parts of DNA at significant locations of a genome.
This requires knowledge of the functions of these parts of DNA, and where they are and should be put.
This may also require knowledge of various proteins and other relevant material. Recent developments of sophisticated artificial intelligence have made important improvements to the necessary knowledge.
Gene editing is used for all of the objectives that I listed earlier. One practical example was putting genes for proteins into the genome of a species of rice that had little or no protein. Such gene-edit foods have given communities access to particular nutrients in their crops where they previously had none. This has improved the diet and health of more than one needy community. Something similar has recently been developed with tomatoes.
The process of making such modifications employs CRISPRs, that is, “Clustered Regularly Interspaced Short Palindromic Repeats”. These are some of the the various kinds of stray strings of RNA attached to proteins, that I mentioned earlier as a random cause of microscopic natural modification.
But these CRISPRs are carefully selected and modified for their purpose. They can be used to identify the right part of the genome, and to cut the genome, and to remove or insert selected pieces of DNA.
Viruses also are similarly used as the tool to insert missing genes. The virus must be made unable to cause infection, but be able to attach to the genome. The required genes are attached to the virus, which is then put into the genome.
These are extremely tiny material to handle, and need great precision..
While they have been used successfully for some decades, errors sometimes occur.
These processes still needs a lot of refining.
Attitudes to Gene Editing
While the well established ancient purposeful modification techniques are regarded to be acceptable and natural, gene editing is regarded, by a high proportion of the populations of several countries, to be unnatural and unsafe. The main issue relates to foods whose production includes gene editing.
At present, many people are also suspicious of, and antagonistic to, other “unnatural” things, such as vaccination, and of fluoridation of drinking water.
All innovations that were based on new aspects of science have caused similar fears, such as the technologies arising from new discoveries about electricity, and automation of factory production, and of transport, and artificial intelligence.
Combining the genomes of radically different kinds of organisms, which could not occur naturally, does suggest the production of weird organisms that could become dangerous and out of control.
This is a situation where all manner of untrue claims are likely to be made and believed.
So far, there does not seem to have been any potential catastrophes with gene editing.
But, while gene editing is doing something that has a good purpose, we cannot guarantee that it will have no seriously difficult outcomes.
Nevertheless, from our point of view, in addition to producing us, and other good things, the huge amount of natural genetic modification also has downsides.
It has produced the many poisonous and dangerous viruses, plants, and animals, and funguses. It has produced SARS-CoV-2. and its mutations. And it has given viruses and bacteria immunity from antibiotics and vaccines.
Over the millenniums we have carelessly taken organisms of all kinds from their ecosystems, and put them into areas where they have no predators. Some of them now have, by natural modification, adapted or evolved to take over in a way that continues to disrupt the previous environment. These are feral animals, plants, bacteria and viruses. They have become very hard to deal with.
This is a serious global problem. Much of it is out of control. We may need to apply, among other things, more purposeful modification to address the situation.
In almost all purposeful processes, there are inevitable mishaps and surprises. It is hard to know how well gene editing is being controlled.
Like all kinds of successful innovations, purposeful modulation will have its downsides. At this early stage, I don’t yet know of any.