Genome Envy

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This article appeared in the Spring 2013 issue of Current Exchange Magazine.

Humans have an inferiority complex when it comes to our genetic material. Back in the early 1970′s, when scientists started characterizing the amount of DNA in different organisms, they were perplexed to realize that we don’t have as much DNA as we should. Or, at least, we don’t have as much as we thought that we should. If DNA is the blueprint of life for all organisms, then why don’t humans, clearly the greatest and most complex organisms, have the most DNA?

And it’s not like it’s a photo finish between us and close relatives like chimpanzees. Some salamanders have as much as 40 times the amount of DNA as humans, and most flowering plants have more DNA than us too. This was a big problem for biologists, but after learning a bit more about the genome, they came up with what seemed like a plausible explanation.

Most of our DNA, scientists said, is junk. The real value of a genome is not total amount of DNA, but the number of genes contained therein. Genes are the real centerpiece of biological complexity. These jewels of the genome are like little recipes encoded in the DNA to make the main cellular components and effector molecules. We weren’t finished finding all of the genes quite yet, but it seemed clear that flowers and salamanders must just have a whole lot more junk than we do, obscuring their true simplicity. In other words, size doesn’t matter if you don’t have the genes to fill the space.

However, as we started sequencing and analyzing genomes of many different organisms, scientists found that this just wasn’t true either. Humans only have around 25,000 genes, while rice, for example, may have up to 50,000 genes. Rice. The kind we eat. How could rice be more genetically exciting than humans? It just… sits there.

This time there was no one obvious higher level of information to appeal to – there were a lot of them. Scientists ascribed our genomic inferiority away to factors like isotypes (a single gene can make several gene products), pseudogenes (duplicate copies of genes in DNA which are no longer functional), and postranslational modifications (little add-ons to gene products that make them act differently).

Looming over all these explanations is the idea of regulation. The genetic program in any one cell-type is usually tightly controlled. Countless genes and pieces of DNA exist only to regulate other genes. There is even a level of regulation scientists refer to as “epigenetics”, gene regulatory changes which persist and can be passed on through cell division absent the signal that set up the original change. Epigenetic regulation states are different through development and across cell types, and change how the same genetic information is interpreted in each context.

So which of these reasons can fully explain the complexity of humans? All of them. Combining all of these different means of regulation gives such an enormous number of potential outcomes that it is easy to see how complex, multicellular organisms can arise. Humans have 25,000 genes, and if you only consider how all of those gene products interact with each other (and most gene products interact with many others), then simply turning them on and off in different combinations already gives an exponential number of possibilities. Add in all the other levels of regulation and modification, and it starts to seem like we’re almost too simple for our genomes.

Organisms, and their genomes, have evolved over billions of years. We may not think of rice as being as complex as us. After all, it can’t even move. But maybe rice had to evolve more complexity because of this. Plants have strategies for warding off predators, fighting parasites, and getting nutrition, each one of them hard-wired into their DNA. They have developmental phases, many different cell types, and a way weirder reproduction strategy than humans do. Who is really to say that we are the more complex organisms? We know so little about most species on the genetic and molecular level, and there is no objective method to determine which are the “higher order” organisms anyway.

Now, humans will always focus on humans. And we should, in order to further understand human health and cure disease. But sometimes, our ego gets in the way of our understanding. If we had accepted long ago that maybe we are not the undisputed kings of complexity, we might, for example, not have written off huge parts of the genome as “junk” DNA (it turns out, it’s not junk). Or we might have made groundbreaking discoveries earlier, such as RNAi, first discovered in worms and thought to be limited to “simple” animals. If we, as biologists, want to study life, we learn the most by studying all the different ways life has succeeded, evolved and thrived – not just how we did.