I feel bad for the gene. Why? Well first, just take a look at his face.
Why is Gene so sad? I think it's because we're always talking about him behind his back, saying things like "it's genetic" and, "so-and-so has the gene for _____." Because we decided who he was decades before we even met him. And the more we learn about him, the more we continue to talk about him as if we've learned nothing. The sadness upon his face seems to say, "How come you never listen?"
The word "gene" was introduced in 1909, but the structure of DNA was not determined until the 1950s. The word "gene" was introduced to mean, basically, a unit of biological heredity responsible for a specific heritable trait.
The idea that each trait had a specific unit of heredity behind it was of great service to the eugenics movement, as I discussed in my introduction to this series. Soon after, it became very useful to the neo-Darwinian Modern Synthesis that unified Mendel's laws of inheritance with Darwin's theory of natural selection as the primary creative force responsible for the diversification of all life from a common ancestor.
Nevertheless, the discovery of molecular genetics, from its inception, began to add much more to the story.
No doubt genes carry heritable information. And no doubt there are variants of each gene called alleles, which contribute to variation in the traits of an organism that are subject to natural selection.
But is that all a gene does? Quite certainly not. With the discovery of DNA, molecular biology began showing that genes are designed to bestow flexibility upon an organism, not simply the ability to inherit characteristics, but the ability to change characteristics in response to the environment and in response to the organism's own needs.
The remarkable ability of the cell to access and utilize its genome, much like we use our computer programs, will be the topic of the next post in this series.
In this post, I'd like to focus on another reason that Gene might be sad. Perhaps when we assume that a heritable disease is "genetic" Gene feels unjustly blamed, and perhaps when we assume that the marvelous and beautiful functional and aesthetic traits of an organism are "genetic" Gene feels flattered but somewhat uneasy of the high expectations laid upon him. Perhaps we are being somewhat demanding in assuming that Gene should carry the burden of biological heredity all by himself.
Please forgive my anthropomorphizing for a moment, as I promise this post actually contains some science, following shortly below.
There is a type of biological inheritance that is not encoded in the DNA within the nucleus of our cells called cytoplasmic inheritance. The cytoplasm consists of the fluid that surrounds the nucleus called the cytosol and all the organelles within it. Organelles are the "little organs" of the cell.
While we inherit half of our nuclear DNA from our mother and half from our father, we inherit mostly our mother's cytoplasm. This includes our mother's mitochondria, which contains its own genome, but it also includes all the other organelles of our mother's egg cell, and these all carry heritable information that is not encoded in any DNA at all, as will be discussed further below.
Cytoplasmic inheritance is commonly discussed in genetics and molecular biology textbooks. One modern way of demonstrating cytoplasmic inheritance is to take a nucleus from one species and transfer it to a denucleated cell of another species. This technique usually fails, demonstrating the need for compatability between the nucleus and the rest of the cytoplasm, but the few success stories are quite fascinating.
Six years ago, for example, Chinese researchers successfully transplanted nuclei from a common carp genetically engineered to express human growth hormone into the egg cells of a goldfish. Remarkably, the cloned hybrid shared certain characteristics that were intermediate between the two types of fish, rather than simply exhibiting the characteristics of the carp. Here's a picture of the hybrid and its parental species:
Sun YH, Chen SP, Wang YP, Hu W, Zu ZY. Cytoplasmic Impact on Cross-Genus Cloned Fish Derived from Transgenic Common Carp (Cyprinus carpio) Nuclei and Goldfish (Carassius auratus) Enucleated Eggs. Biology of Reproduction. 2005;72:510-515.
The cloned hybrid is on the left. The hybrid's nucleus came from the carp, shown in the middle, and its cytoplasm came from the goldfish, shown on the right.
The authors say there was little difference in the appearance of the hybrid from the carp, and indeed, the hybrid looks a lot closer to the carp than to the goldfish. However, other authors have pointed out that the body shape of the hybrid is more rounded than the carp and thus somewhat intermediate between the carp and goldfish. Personally, the tail looks to me like a cross between the two types of fish.
In any case, the authors provided a remarkable finding about the number of vertebrae. The goldfish had 26 vertebrae and the carp had 33-36 vertebrae. Even though the nuclear DNA came from the carp, most of the cloned hybrids had 27 or 28 vertebrae while another had 26 and another had 31. This shows that the cloned hybrid had a number of vertebrae closer to the goldfish that provided the cytoplasm than to the carp that provided the nucleus.
Moreover, all of the cloned hybrids were sterile. Sterility is common among true hybrids of different species where half of the nuclear DNA comes from one species and half from another. Here, the same results are achieved when the nuclear DNA comes from one species and the cytoplasm comes from another, suggesting a certain type of equivalence between the importance of information in nuclear DNA and information in the cytoplasm.
In general, cytoplasmic inheritance is tacitly assumed to be a function of mitochondrial DNA. This is based more on faith than on evidence, and there are a two good reasons to think it is probably not entirely true.
First, although the mitochondria contains its own DNA, most of its proteins are actually encoded by nuclear DNA, and mitochondria do not appear to export any of the proteins that they make themselves. Thus, the mitochondrial DNA might make a meaningful but perhaps relatively minor contribution to the characteristics of an organism.
Second, there is a massive amount of information contained in the cytoplasm itself that is not encoded by any genes, whether nuclear or mitochondrial, but is nevertheless inherited from generation to generation.
To understand how this is possible, let's take a look at what the inside of a cell looks like.
The cell is organized into a number of different compartments by a continuous system of membranes. This system of compartmentalization is absolutely essential for cellular function and for producing the biological characteristics of an organism in conjunction with the information coded in DNA.
The image is, of course, simplistic. Even within one organelle's membrane, there are further regional divisons in structure and function, and there are many fascinating localized structures that are not shown in the picture.
What is important here, though, is another point. The information needed to produce these membranous compartments is only partly coded for in DNA. Part of it resides in the membrane itself, is heritable, and is not coded for anywhere in the DNA.
Molecular Biology of the Cell, the definitive guide to mainstream molecular biology, decribes why this is so in its twelfth chapter, "Intracellular Compartments and Protein Sorting."
Each membranous organelle is to some degree distinguished by the types of lipids it contains, but these are in turn determined by its unique set of proteins. The proteins themselves are major determinants of the oragenelle's function. These proteins have signal sequences associated with them that direct them to specific organelles.
But here's the catch! What facilitates the matching of the signal sequence to the membranous organelle for which the protein is destined? The proteins in the membrane. That's right, if there are no protein transporters in, for example, the endoplasmic reticulum, then those signal sequences that destine a protein to the endoplasmic reticulum can't be recognized by anything and have no meaning at all.
In the case of the endoplasmic reticulum, the phenomenon is even more striking, since the endoplasmic reticulum actually has to make those proteins before they can get transported anywhere anyway.
Thus, it is not just the nuclear DNA that defines the membrane, but the membrane itself. Here's the conclusion of the authors of Molecular Biology of the Cell (p. 704) in their own words:
Thus, it seems that the information required to construct an oragenlle does not reside exclusively in the DNA that specifies the organelle's proteins. Information in the form of at least one distinct protein that preexists in the organelle membrane is also required, and this information is passed from parent cell to progeny cell in the form of the organelle itself. Presumably, such information is essential for the propagation of the cell's compartmental organization, just as the information in DNA is essential for the propagation of the cell's nucleotide and amino acid sequences.Thus, there exists absolutely critical information that is biologically heritable that is not coded for in the DNA.
To what extent do variations in this information contribute to variation between and within species?
This is a mystery that will only begin to be unraveled when more scientists drop the myopic and completely false view that organisms are largely vehicles meant as containers for self-propagating genes — a view that was always preposterous but is now more than ever completely proven false — and join the ranks of computational systems biologists who look at physiology as an integrated whole and attempt to actually ask and answer such questions.
That's not to say that most scientists actually hold such a myopic view, but scientists who study heredity essentially universally study variations in DNA sequences. The fact that we know of many examples where variations in DNA contribute to variations in heritable characteristics and do not have a similar body of knowledge about non-genetic heritable information may simply be a result of the many people asking the first type of question and almost no one asking the second type of question rather than being a result of a greater relative frequency of that type of biological inheritance.
On the other hand, though we still have a great deal to learn about gene expression, we do have a very impressive body of knowledge about how cells access, utilize, control, and even in some cases restructure their genomes in response to their own needs and the needs of the organisms of which they are part. That will be the subject of the next post in this series.
Read more about the author, Chris Masterjohn, PhD, here.