Last night I listened squeamishly to my 13-year-old daughter and her friends compete in a (loud!) Fear-Factor-type eating contest in the other room (a sample dish: gummi worms covered in coleslaw - shudder). Fortunately for her (and all of us, really), the old adage “you are what you eat” is a vast oversimplification of nutrition science; many factors actually influence our overall health and body composition.
A similar simplification existed at one time in genetics, when it was believed that the DNA sequence of our genes determined our biological destiny. But over time scientists have learned that many variables affect how, when and even to what degree these genes are expressed, or transformed, into proteins. For instance, I may have the same DNA sequence for gene A as my friend, but I may make more, or fewer, molecules of protein A than she does, and therefore have a significantly different biological outcome. Unfortunately, it's been difficult to accurately quantify and compare protein levels among individuals and groups.
Now research led by Stanford geneticists Hua Tang, PhD, and Michael Snyder, PhD, published yesterday in Nature (subscription required), has shown that these variations in gene expression levels are inherited over generations. In other words, your levels of expression of individual genes is likely to be similar to that of your parents. What's more, genes involved in common processes tend to vary in similar ways - indicating a high degree of coordination of expression. As Tang explained in an e-mail to me:
We've found that the abundance of many proteins varies considerably among individuals, and we have identified numerous DNA variants that may influence the protein expression of a neighboring gene. We also showed that proteins that co-vary tend to have related biological functions or physical interactions.
The researchers used a sophisticated variation of a technique called quantitative mass spectrometry to determine the relative level of nearly 6,000 proteins in cells from 95 people from around the world. Until recently, most researchers relied on an indirect, and inexact, method that estimated protein levels within a cell based on the prevalence of RNA messages encoding that protein. Co-first author and research associate Sophie Candille, PhD, (who co-authored the research with postdoctoral scholar Linfeng Wu, PhD) explained:
RNA is in fact an intermediary molecule in the expression of the protein-coding genome. Proteins are the end product and active agents of the cell but their quantification has been challenging and therefore has lagged behind that of RNA.
By analyzing which proteins co-vary, the researchers were able to identify new functional groups that hint at previously unknown protein networks and interactions. Postdoctoral scholar and co-first author Linfeng Wu, PhD, concluded:
This research is important because many proteins are involved in the human immune response and diseases such as cancer. Therefore, the DNA variants that influence gene expression at the protein level are likely to be associated with disease phenotypes.
As Wu explained, the researchers are particularly interested in understanding how variation in protein expression levels affects disease risk or physical attributes. In my case, I can't help wondering whether I have a genetic predisposition to nausea when I hear talk of eating bananas with Baconnaise or Spam with chocolate sauce (gag). But maybe, my reaction isn’t all that unusual?
Previously: Stanford geneticist talks tracking biological data points and personalized medicine
