Genetically modified organisms

This is not an easy topic. Most of us misunderstand and very few of us know enough to grasp what genetic modification actually is. This includes the people who do it, who discover repeatedly that they were mistaken about some expected result. Genetics itself has changed enormously in the last couple of decades or so. What most people think of as genetic modification is simply not what it is. In addition, one of the first successful GMOs was designed to improve corporate profits, with improved crop yields as a side effect. This has raised suspicions about the motives the gene modifiers.

I’ll give my current understanding of GMOs, with two warnings: first, the following is inevitably incomplete and certainly wrong or misleading in several places. Second, the news about genetics is changing very rapidly.

Two very basic and fundamental points:
A, The genome (the collection of genes on all the chromosomes) is not like a blueprint. A much better metaphor is “recipe” or “program”. Like any program, different parts of the code are running at any given time. That’s why we have skin cells, and muscle cells, and liver cells, and brain cells, and so on, all of which contain the complete genome. That’s why a scratch or cut heals: the genes that promote skin cell growth and migration to heal the cut are normally inactive. That’s why we are awake or asleep: genes in neurons turn on and off, the neurons function differently, and we sleep or wake up. We say a gene is “expressed” when it’s doing its work.

B, Genetic modification happens all the time. New varieties and species all arise from genetic modification that’s passed on from one generation to the next. However, a large chunk of the genome does not change: natural selection preserves genes that necessary for life and reproduction. That’s why we share about 20% of our genome with snails. Natural selection ignores genes that have no net effect one way or the other; however, “genetic drift” may change the frequency of these genes. That’s a major reason that people from different parts of the world look different.

We humans have used selective breeding to concentrate genetic variations to suit ourselves.. This method gave us wheat, corn, potatoes, tomatoes, and so on. As well as a huge variety of dogs, cows that produce gallons of milk, woolly sheep, gentle buffaloes, and so on. Whenever you breed for some desirable trait, you also breed for other traits, some of which may be undesirable (think tough, bruise-resistant tomatoes with no taste, or roses lacking fragrance). Some selective breeding has resulted in infertile plants (bananas), or plants that need human help to breed (corn).

Selective breeding is possible because of the following mechanisms of genetic modification.

1) Recombination. The prime mode of modification from one generation to the next, and the reason none of us is a clone of our parents. Prime example: Apples. They don’t breed true. All of the delicious varieties we enjoy are the result of recombination. The only way to propagate these varieties is by cloning (grafting from one tree to another). If the chain of cloning breaks, that variety of apple disappears.

2) Hybridisation, also known as crossing. Easy with varieties of the same species, more difficult with related species. Easier with plants than with animals. It happens spontaneously, especially among microbes. Some hybrids between related species are fertile, which raises the question of whether they are new species, and whether the related species are really different species. "Species" is a fuzzy concept.

3) Mutation. Most mutations are repaired as they happen, others kill the cells in which they happen, the rest survive. If a surviving mutation is in an egg or a sperm, it may be passed on to the next generation, in which case it may spread through the species and modify it. Hairless cats are an example.

4) Gene exchange. This happens directly among bacteria, even across species, and is the reason that resistance to antibiotics has spread faster than originally estimated. It’s also the reason bacteria can be used to produce useful materials. It also happens with plants, and occasionally with vertebrates that breed externally, such as fish. Some plants even require “foreign” pollen to reproduce (currants, for example).

5) Polyploidy: more than two sets of chromosomes. Most common among plants (estimates range from 30 to 80% of all plant species). It’s possible to manipulate the process, and so produce new varieties of plants.

6) Methylation: during the organism’s life, methyl groups are attached to the genome, for many different reasons. This affects the gene expression. Methylation happens in all organs, including reproductive organs, which means it can affect gene expression for at least the next generation.

7) Viral or bacterial infections which alter the genome. Prime example: tulips. Viral infection of the bulb affects the colour, shape, etc of the of bloom. It does not affect the seed, which means that the only way to propagate such varieties is by cloning them. Viral infections work by inserting genes into the host DNA, so that the infected cell then produces viruses.

8) Artificial gene modification. Humans have been doing this as long as they’ve been human, through selective breeding. Later, humans discovered cloning (grafting), which led to plants that cannot propagate on their own (seedless watermelons, bananas).
     What’s new is the ability to use some of the natural processes that change DNA. In particular, enzymes that bacteria and viruses use to replace bits of host DNA with the infector’s DNA can be used to insert or replace genes that are useful from our point of view. The most recent method of altering DNA is CRISPR, a method to edit DNA directly, in order add, delete, or replace a gene.

But it’s not easy. Any change to DNA may have unexpected effects. Manipulating the genomes of bacteria is easiest: they are naturally prolific adapters of foreign genes. It’s more difficult with plants, and most difficult with animals. In general, it’s easy to replace a gene, more difficult to insert one. Removing a gene is easy enough: it’s been done with selective breeding of lab mice.

Replacing genes is the basis of gene therapy, which has had some small success. Exchanging genes from the same species is a good way to produce new varieties. Selective breeding is the slow way; CRISPR is quicker.

Inserting genes is difficult because the gene may not even work, let alone work as desired. The success of doing this is highest with bacteria, which do it naturally, and with abandon. For example, there are some bacteria that can eat some plastics. Would be nice to grow a bacterium that needs some specialised environment in a vat, dump in the plastic, and drain off the waste.

Editing the genome, by replacing one version of a gene with another version, turns out to be relatively easy. It’s also hugely successful: after all, a different version of the same gene will usually be expressed just like the one you replaced. The genes for blue eyes and brown eyes are simply different versions of the same genes.

An important fact is that related species share most of their genes. How much do they share? That depends on how closely related they are. We are more closely related to horses than to snails, so we share more genes with horses than with snails. But we are more closely related to snails than to roses, so we share more genes with snails than with roses. Sharing genes with other organisms makes gene exchange possible.

But it’s not really that simple. Just because we share certain genes doesn’t mean that they work exactly the same way. The gene’s environment affects gene expression. Which genes, when, and to what effect, all depend on the gene’s environment. That environment operates over several systems: , first, the cell itself, ie, which other genes are working in that cell. Then the organism itself, ie, which organ the cell is part of. Then the physical environment of the organism, ie, temperature, food, and so on. Finally, other organisms, ie, mates, predators, food sources, and so on. Pretty complicated, really.

And that’s why genetic modification, by any method, is more art than science, and results in more failures than successes.

Nevertheless, we humans have been doing it as much as possible for a long time. The newest insights into how genes work and how to change the genome have merely made the process quicker, and a little more certain.

Revised 2019/03/21