Understanding DNA in the Age of Omics

Omics sounds a bit like Olmecs, who were a culture that flourished in Mesoamerica near the Gulf of Mexico between 1500 and 500 BCE (you can read about them here). Omics refers to the blossoming of fields within biology that attempt to characterize the totality of a particular class of molecules within an organism. The first and most influential Omic (or -omic) is genomic study. Biologists who study genomics are attempting to characterize the diversity in structure and function of genes (DNA molecules) within their study species. Other Omics include proteomics (proteins), transcriptomics (transcribed RNA), lipidomics (lipids), and many more. The age of Omics represents a change in the way we study biology that has been caused by new technologies that allow us to capture and analyze vast amounts of data. 

One of the problems with Omics is trying to wrap your brain around the vastness of the molecular world. We know that DNA consists only of four bases: A, C, G, and T; but going from those simple letters to a functioning animal is where it gets sticky. Here is how I think of DNA. If you wanted to tell someone how to build an animal, like, say, an echidna, how would you do it? If it were me, I would write a manual called How to Make an Echidna. If you said that you would make a gif like those little recipes that people love to share on Facebook and call it: Make a Vegan Echidna Using These Six Easy Steps!, maybe this blog post is not for you. Okay, so an echidna manual. Most manuals we make contain a lot of numbered steps and diagrams. One problem we often run into is translation. You can’t make an echidna if the instructions are in Cyrillic. Fortunately, all organisms on earth use the same language, so don’t have to worry about this problem. Diagrams would be handy, but biology hasn’t figured that one out yet. Instead, that means the instructions need to be many times longer to explicitly describe what the diagrams would show. So now our How to Make an Echidna Manual is a very very thick encyclopedia-looking book. It contains everything on how to build an echidna. It has simple descriptions of how to build the proteins that make up its hair to complicated instructions on how to build and use the tools needed to make the hair and even the tools to sense when more hair needs to grow. It’s a long manual. Turns out that having one book this size is a pain in the ass for cells to work with. Plants and animals’ (and other eukaryotes’) solution to this problem is to package the manual into different volumes called chromosomes. Humans have 46 volumes to their manual, or genome, echidnas have 63 in the male and 64 in the female (don’t ask me why, but you can read here).
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Now that we have our manual, we have a problem. Not every echidna is the same, which is actually a good thing for echidnas as a species. How did we get different varieties of echidnas? One way is mutation. The little proteins that act like nanoscopic monks relentlessly copying each page of the manual for making baby echidnas are very good at their jobs, but they are not perfect. Once in ten billion transcriptions they make a mistake and a mutation occurs. Over a very long period, these mutations can result in differing manuals between organisms. Sometimes mutations can result in a page of the manual that contains instructions on how to move itself to a different part of the manual. These pages are known as transposons or ‘jumping genes’. Regardless of how these variations arise, they are important for the study of any organism. Scientists are beginning to be able to study differences in genomes to learn a lot about how species’ DNA works.

What does this actually look like? My research is concerned with determining differences between the genomes of a plant in different areas of the continent. I can use these differences to learn things about how my plant is evolving and how it has spread through different regions. The answers are all there in the manuals, if you read them right.

How can we figure out these differences in manuals? The easiest way would be to read all of the manuals of all of the plants I want to study. Well, I could do this, but only if I had a few million dollars to throw at the problem. The best compromise that currently exists is called Genotyping By Sequencing (GBS). Essentially, this method randomly rips out millions of sentences from the manual of each sample using DNA cutters called restriction enzymes and compares them between samples. Due to the way sequencing technology works, it is cheap and fast to sequence these sentences, even if there are millions of them. Next, I can line the sentences up next to each other, and pick out the differences in letters, called Single Nucleotide Polymorphisms (SNPs). From there, I can do analyses like, “Hey! That plant from New York has 156 differences from the Maine one, but only 25 differences from the New Jersey one! The New York is more closely related to the Jersey one.” Or, “Hey! None of the plants from Virginia have any differences! They must be reproducing asexually.” The actual analyses are more complicated, but that’s how I imagine them in my brain.

A few years down the road, sequencing and computing will likely get to the point where we can easily read and analyze whole genomes, but for now, GBS is the best way to investigate large scale differences in populations of plants and animals. From a small DNA sample from a few hundred individuals, I could tell you how long ago the first Golden Retriever was bred. I could tell you whether or not corn in Iowa farms is genetically different from that in Kansas farms. With the DNA recovered from feces, I could tell you how many generations are left before Snow Leopards go extinct. Or I could tell you how building more roads is breaking apart populations of echidnas. The age of Omics is about an unprecedented ability to understand the living world around us by learning the right way to read the manual that each and every organism carries around within it, the genome.

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For more facts about echidnas (some of which may or may not actually be true)

Image credits
Kitchenbowl Raises $1M To Help Users Create Easy-To-Follow, GIF-Heavy Recipes
http://spiderdiaries.richmond.edu/danny17/?assetid=7608eb09ac1c041919d8b871e47f1f3a
http://voices.nationalgeographic.com/2014/02/08/echidnas-australia-tasmania-science-animals-weird-stewart-nicol/