The human genome contains more than 20,000 protein-coding genes, which carry the instructions for proteins essential to the structure and function of our cells, tissues and organs. Some of these genes are very similar to each other because, as the genomes of humans and other mammals evolve, glitches in DNA replication sometimes result in extra copies of a gene being made. Those duplicates can be passed along to subsequent generations and, on very rare occasions, usually at a much later point in time, acquire additional modifications that may enable them to serve new biological functions. By starting with a protein shape that has already been fine-tuned for one function, evolution can produce a new function more rapidly than starting from scratch.
Pretty cool! But it leads to a question that’s long perplexed evolutionary biologists: Why don’t duplicate genes vanish from the gene pool almost as soon as they appear? After all, instantly doubling the amount of protein produced in an organism is usually a recipe for disaster—just think what might happen to a human baby born with twice as much insulin or clotting factor as normal. At the very least, duplicate genes should be unnecessary and therefore vulnerable to being degraded into functionless pseudogenes as new mutations arise over time
An NIH-supported team offers a possible answer to this question in a study published in the journal Science. Based on their analysis of duplicate gene pairs in the human and mouse genomes, the researchers suggest that extra genes persist in the genome because of rapid changes in gene activity. Instead of the original gene producing 100 percent of a protein in the body, the gene duo quickly divvies up the job . For instance, the original gene might produce roughly 50 percent and its duplicate the other 50 percent. Most importantly, organisms find the right balance and the duplicate genes can easily survive to be passed along to their offspring, providing fodder for continued evolution.
This discovery comes as something of a surprise. Scientists have theorized that the original and duplicate genes might act in different parts of the body. Or, perhaps more rarely, one of them might take on a different function.
In the study, Xun Lan and Jonathan Pritchard of Stanford University, Palo Alto, CA took advantage of data on human gene activity generated in The Genotype-Tissue Expression (GTEx) Project, supported by NIH, to learn how gene changes contribute to common diseases. The data include the tissue expression levels of more than 1,400 human gene pairs that had been duplicated in mammals at some time in the distant past. The researchers had measures of gene activity representing 10 different people and 46 human tissue types, including the brain, skin, muscles, and lungs. They also did the same kind of analysis in gene expression data from 26 mouse tissues. (Fun fact: The protein-coding DNA sequences of humans and mice are 70 percent identical! )
Lan and Pritchard found that duplicate genes sometimes show roughly equal activity across body tissues. In other cases, while one gene did most of the work, the other pitched in to make up the difference. Either way, the genes seemed to continue performing essentially the same function in all of the same tissues.
Their analysis suggests that much more rarely—only 15 percent of the time—duplicate genes in humans and mice have clear expression differences in different parts of the body. The gene pairs showing that pattern also tended to be a lot older, suggesting that it takes a long time for genes to act differently in different tissues or to evolve new functions.
Lan and Pritchard say that duplicate genes likely continue working with the original because the two copies tend to occur in tandem, one right next to the other. As a result, they also tend to be under the same set of cellular controls. Those extra copies of the gene can be maintained because balance is easily restored. But differences between tissues or wholly new functions require a bigger rearrangement to occur, physically separating the original and duplicate from each other to allow them to act independently.
More research will be needed to confirm these findings. But this work raises some fascinating possibilities about how evolution works over long periods of time—and highlights the rapid progress that is now being made in understanding the human genome.
 Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals. Lan X, Pritchard JK. Science. 2016 May 20; 352(6288): 1009-13.
 New comprehensive view of mouse genome finds many similarities and striking differences with human genome. National Human Genome Research Institute/NIH. 2014 November 19.
What is a gene? (National Library of Medicine/NIH)
The Genotype-Tissue Expression Project (National Human Genome Research Institute/NIH)
Pritchard Lab (Stanford University, Palo Alto, CA)
NIH Support: National Institute of Environmental Health Sciences; National Institute of Mental Health