In a genome study, we can get the sequence of the DNA in some organism. In a metagenome study, we can get the sequences of the DNA in some ecosystem.
We’ll be looking at examples of both today, but first, why care about genome sequences to begin with? Genomics can inform the history of life as we track changes in genes (for example, tracing your domestic Maltese back to a wild wolf). Endogenous retroviruses mark events in a species’ past when it was infected by some virus. Transposons jump around genomes, sometimes taking DNA with them as they go. We can track populations this way, and try to fit together clues about an organism’s biological past.
We can also use it to inform medicine. Sequencing a genome is the first step to figuring out what parts of it cause inheritable diseases. If we can understand the underlying genetic causes, we can (hopefully) better treat it.
Genomics can also be a realm of sheer discovery! When exploring a world new to us – maybe a hydrothermal vent, or the canopy of the tallest living trees, or the insides of a weird plastic-eating bug – we want to know what’s there and what it’s doing. Sequencing all the DNA in some microbiome gives us the first insight into obscure new worlds.
Kicking Off the New Millenium
The human genome wasn’t sequenced until 2000, published in Nature in February the following year. At the time, the Human Genome Project was a monumental project. Now, sequencing a genome is a well-worn protocol, a casual routine for many molecular biologists. What have we learned since then?
Well, for starters, we learned that our first read published in 2001 was kind of a bust. It had 250,000 gaps (give or take a few) and various nucleotide errors.
Since then, however, we’ve updated our knowledge of the human genome with genomics samples from individuals all around the world. With it, we’ve gained incredible insights into cancer, inheritable Mendelian diseases, and polygenic disorders (more complicated genetic diseases that involve multiple genes). With this knowledge has come advanced research for treating this disorders.
The human genome also led to the remarkable discovery that most genes do not encode proteins. If it’s not supposed to be transcribed and translated into proteins, what exactly is it doing?
We’re still figuring some of that out, but in the meantime, we’ve learned that there are jumping genes (which yes, jump around the genome, to various purposes), small non-coding RNAs (including ones that silence those pesky jumping genes from causing too much of a disturbance), and large intergenic non-coding RNAs (another regulator, possibly, for the cell cycle, protein expression, and more).
In the case of Mendelian diseases, where the problem is caused by a single gene, we’ve been able to identify small molecule therapeutics. For example, TGF-β needs an inhibitor in the case of Marfan Syndrome. Even disorders caused by the interaction of multiple genes can be informed by a genomics study, however. For example, among autoimmune disorders as diverse as diabetes, arthritis, and coeliac disease have been found to have a few regulatory pathways as a common causal factor.
Quaff, Oh Quaff This Microbiome
Monkey Cup, genus Nepenthes, is a carnivorous plant with leaves-turned-pitchers. The pitchers trap unsuspecting insects, which are eaten in the digestive fluids at the bottom of the cup. It turns out that the pitcher is also home to a diverse microbiome, with many bacteria that may well play a role in breaking down insect bodies.
In this case (Chan et al. 2016), a study is a metagenomics study – all the DNA inside Monkey Cup pitchers was sequenced, to get an overview of the species living in this miniature ecosystem.
Samples resulted in over half a million DNA reads, each about 350 base pairs long. They identified 29 bacterial phyla, representing over 600 species, with 27% unidentified, potentially new creatures.
Metagenomic analysis was just the beginning. They also wanted to know – what are all these bacteria actually doing in there? There are plenty of enzymatic assays you can run to figure this out. Specifically, they tested if the bacteria can turn various complex carbon compounds into sugar (starch, cellulose, xylan, chitin). They also tested for proteolytic activity, or breaking down proteins into peptides or amino acids. All this breakdown of complex biomolecules (exoskeletons are primarily chitin, for example) into simple sugars and peptides may very well assist the Monkey Cup’s ability to digest and consume the insects it captures.
There were plenty of bacteria cultures that were unidentified in the Monkey Cup pitchers. There may be even more new species, however. After all, we are only able to sequence “culturable” species – bacteria that will grow on our petri dishes and food sources. What if some bacteria in the pitchers are picky about lab-grown environments? While previous studies have suggested limited microbial diversity inside these carnivorous plant pitchers, this paper suggests just the opposite.
Monkey Cup grows in a barren environment; its roots can collect water, but not much in the way of nutrients necessary for life. It appears that with this diverse, enzymatically active microbiome empowers it to thrive.
Chan, X. Y., Hong, K. W., Yin, W. F., & Chan, K. G. (2016). Microbiome and Biocatalytic Bacteria in Monkey Cup (Nepenthes Pitcher) Digestive Fluid. Scientific Reports, 6, 1–10. https://doi.org/10.1038/srep20016
Lander, E. S. (2011). Initial impact of the sequencing of the human genome. Nature, 470(7333), 187–197. https://doi.org/10.1038/nature09792