The Deflated Ego Problem

"How humans get away with having a small genome"

Believe it or not, that's actually the subtitle of a short article in this month's issue of SEED (June, 2007). Who knew that humans have a small genome?

The author, Yohannes Edemariam, is a frequent contributor to SEED. He lives here in Toronto. Edemariam begins with the usual mythology designed to make you think there's a problem with the human genome [see Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome]. This "problem" cries out for an explanation ...

Given our complexity—our capabilities for abstract thought, language, the building of civilizations—biologists were surprised at the relatively small number of genes we possess when they first began studying the human genome. It has since been become clear that our 20,000 to 25,000 genes can be manipulated by processes that statistically enhance the variety of ways in which each gene becomes manifest in our physical makeup.

This is typical of the rhetoric that pervades the popular science literature and, more importantly, the real scientific literature. The scientific evidence shows that our genome has about 25,000 genes and that's not much more than nematode worms or fruit flies. What this tells us is the same message that developmental biologists have been shouting for 35 years—small changes can have big effects. Clearly, some people haven't been listening.

The human chauvinists are disappointed that our genome isn't as complex as our brains and behavior suggest (to them). They expected to see tangible evidence that humans were at the top of the heap. I call this "The Deflated Ego Problem." The question before us is whether this is a real scientific problem or whether it stems from an incorrect understanding of evolution and development.

Having barely survived a major blow to their ego when the human genome turned out to have fewer than 30,000 genes, the deflated ones have fought back with various schemes to explain the "paradox." What they look for is some special mechanism that we humans possess in order to get a bigger bang for our buck. In other words, they're looking for their missing complexity in other places.

Ironically, the chauvinists don't realize that their "problem" can only be solved by discovering hithertofore unknown mechanisms that are confined to humans, or possibly mammals. The reason is obvious. If the mechanism is universal then fruit flies and worms have it as well and we can't use the new-found genome complexity to rationalize why we have so few genes compared to them. After all, the goal here is to explain why we only have a few thousand genes more than those "simple," "primitive," species and the explanation won't work if we all have the same complexity-generating mechanisms. I say "ironically" because many of the special mechanisms being proposed were first discovered in these "primitive" species. Now they're being used to solve the Deflated Ego Problem.

So, what are these magical complexity-generators that "statistically enhance the variety of ways in which each gene becomes manifest ...?" Are they going to solve the Deflated Ego Problem?

I'm not going to tell you which one is being promoted in the SEED article. You'll have to buy the magazine—which I highly recommend in spite of its flaws—to find out the answer. Here's the latest list of the sorts of things that may salvage your ego if it has been deflated.

1. Alternative Splicing: We may not have many more genes than a fruit fly but our genes can be rearranged in many different ways and this accounts for why we are much more complex. We have only 25,000 genes but through the magic of alternative splicing we can make 100,000 different proteins. That makes us almost ten times more complex than a fruit fly. (Assuming they don't do alternative splicing.)

2. Small RNAs: Scientists have miscalculated the number of genes by focusing only on protein encoding genes. Our genome actually contains tens of thousands of genes for small regulatory RNAs. These small RNA molecules combine in very complex ways to control the expression of the more traditional genes. This extra layer of complexity, not found in simple organisms, is what explains the Deflated Ego Problem.

3. Pseudogenes: The human genome contains thousands of apparently inactive genes called pseudogenes. Many of these genes are not extinct genes, as is commonly believed. Instead, they are genes-in-waiting. The complexity of humans is explained by invoking ways of tapping into this reserve to create new genes very quickly.

4. Transposons: The human genome is full of transposons but most scientists ignore them and don't count them in the number of genes. However, transposons are constantly jumping around in the genome and when they land next to a gene they can change it or cause it to be expressed differently. This vast pool of transposons makes our genome much more complicated than that of the simple species. This genome complexity is what's responsible for making humans more complex.

5. Regulatory Sequences: The human genome is huge compared to those of the simple species. All this extra DNA is due to increases in the number of regulatory sequences that control gene expression. We don't have many more protein-encoding regions but we have a much more complex system of regulating the expression of proteins. Thus, the fact that we are more complex than a fruit fly is not due to more genes but to more complex systems of regulation.

6. The Unspecified Anti-Junk Argument: We don't know exactly how to explain the Deflated Ego Problem but it must have something to do with so-called "junk" DNA. There's more and more evidence that junk DNA has a function. It's almost certain that there's something hidden in the extra-genic DNA that will explain our complexity. We'll find it eventually.

7. Post-translational Modification: Proteins can be extensively modified in various ways after they are synthesized. The modifications, such as phosphorylation, glycosylation, editing, etc., give rise to variants with different functions. In this way, the 25,000 primary protein products can actually be modified to make a set of enzymes with several hundred thousand different functions. That explains why we are so much more complicated than worms even though we have similar numbers of genes.

I don't think any of these explanations are valid because I don't think there's a problem that need explaining in the first place. I wish scientists and science writers would stop pretending that the Deflated Ego Problem is a real scientific problem and I wish they'd stop promoting their favorite, logically flawed, arguments to defend it.

Since that ain't going to happen, I'd like to offer a bit of advice designed to spare us from rhetorical overload. Here's a little template that all science writers can use next time they're tempted to write about this "problem."

(I/we/the authors) believe that the Deflated Ego Problem is a real scientific problem. (I/we/the authors) propose that explanation number (1/2/3/4/5/6/7) will account for the fact that we have too few genes.