Show Me The Science Month Day 15

What happens when a big chunk of your genome is accidentally copied? Bad things could obviously happen when when sudden and dramatic changes are made to your genome (which is why we wear sunblock on the beach and lead shields when getting X-rayed). Recent studies have found that accidental duplications in the genome (which can change the copy number of sets of genes) are involved in a growing list of diseases, including autism, psoriasis, and susceptibility to AIDS. And yet we also know that big DNA duplications aren't always harmful, because we can find ancient duplications in our genomes that harbor genes filling useful roles in our physiology.

How frequently do these large duplications arise, and what role have they played in human evolution? A group led by Evan Eichler, at the University of Washington, aided by the DNA sequencing powerhouse of the Genome Sequencing Center at Washington University (in St. Louis - not the same place as the University of Washington!), has studied these questions by looking for big, duplicated chunks in our closest relatives - the great apes. Their results show that big DNA duplications have probably played an important role in the evolution of our species.

Whenever you make gametes (sperm and egg cells), your cells decide to make things exciting by shuffling around chunks of your chromosomes. You inherited one copy of each chromosome from both your mother and your father, but you don't pass on those chromosomes to your kids in the same condition that you received them in. To generate some genetic diversity, the precursors of your sperm or egg cells swap bits of maternal and paternal DNA. The result is that each chromosome you pass on to your kids is a mix of DNA from both your father and your mother.

This genetic swap meet can go horribly wrong sometimes, resulting in the duplication of large chunks of DNA. In fact, out of 3 billion DNA bases (or 'letters') in the human genome, almost 18 million of them come from large stretches of duplicate genetic material, according to Eichler's results. These duplication events were large, each encompassing 20,000 bases or more. (Even more of our genome is duplicate material if you count smaller duplications.)

Evolutionary patterns start to emerge when you look at this duplication phenomenon in other great apes. These duplications are very specific, accidental events, so by comparing duplications in the human genome with duplications found on other ape genomes, scientists can pinpoint when the duplication occurred. For example, if a particular duplication is found in humans and chimps, but not in gorillas or orang-utans, then we know that the duplication event occurred after the human-chimp lineage split off from gorillas, but before the split between humans and chimps. The alternate possibility is that the exact same duplication occurred independently in humans and chimps (and not simply once in a shared ancestor), but this possibility unlikely to the point of impossibility.

Exactly identical duplications don't happen, but similar, almost identical duplications turn out to be fairly common, Eichler's group found. Certain regions of primate genomes are accident-prone, primed for duplication. By examining DNA from different, unrelated gorillas, the researchers found genome regions that had duplicated multiple times, independently in each gorilla (or its near relatives). The same region was duplicated independently in chimps - the duplication wasn't exactly identical, but it was close.

What makes one region of the genome primed for duplication? Prior duplication, it turns out. The researchers found that genome regions which had duplicated in the human-chimp common ancestor were close to duplications that had occurred in the human-chimp-gorilla-orangutan common ancestor. This is actually not too surprising; the molecular 'scars' left by a duplication event have traits that facilitate future duplications.

Eichler's group found that large bursts of duplication occurred in the human-chimp-gorilla ancestor and the human-chimp ancestor. This does not necessarily mean that duplication events became biochemically more frequent (although that's conceivably possible); it just indicates that duplications managed to spread through the gene pool at a very rapid pace. To understand what this means, let's step back and think about how a duplication that happened 10 million years ago in one individual human-chimp-gorilla ancestor shows up in your genome. To survive to the present day, the duplication event had to get passed on, that is, 1) occur in a sperm or egg cell and 2) stay in the gene pool long enough to become 'fixed' - present in every single member of the species living today.

This means that the some of these duplications probably had some survival value, and in fact Eichler's group found the imprint of natural selection in some of the genes residing in duplicated blocks, corroborating the idea that some duplications were helpful. Not all of the duplication events had to have survival value (some probably become fixed in the gene pool by sheer chance), but some of them clearly did.

So why was there a burst of genome duplications that got themselves fixed into our gene pool? Without further research, we can only speculate at this point, but it's possible that something caused these large duplications to suddenly become a major source of genetic variation, which is the raw material evolution acts on. Eichler's group notes that, for some currently unknown reason, other sources of genetic variation (such as small mutations at individual DNA bases) were slowing down among apes during this time. In a small population of hominids, possibly facing major environmental change, large dramatic duplications could have been the most rich source of helpful mutations available. The results of Eichler's study suggest that, in a pinch, big mutational changes may be helpful.

My apologies to those of you who have been following along; my grant proposal deadline temporarily derailed our 30 Days of Evolution Blogging. The deadline has passed, and I'm back in business now, so join me tomorrow, here at Adaptive Complexity, for day 16 of 30 Days of Evolution Blogging Evolution as a science is alive and well. Each day I will blog about a paper related to evolution published in 2009.

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