All organisms diverge in their size, appearance, physiology, and nutrient requirements. Instructions for an organism to live, reproduce and diverge from other organisms lay in its genome.
The genome is the complete, unique set of genetic material that an organism has. A recent study tells us that even the human genome of identical twins differs by 5.2 mutations on average.
In any environment on the Earth, there are millions and billions of unique individual organisms, with each organism having unique microbial genomes.
On the other hand, the word metagenome describes all the genomes in a sample from any environment.
To summarize, a genome is an individual organism’s genetic makeup and a metagenome is a collection of genomes from many individuals within an environment and/or sample.
What is metagenomics?
Metagenomics is the study of the metagenome, the complete set of genomes in a sample. The term metagenomics usually refers to the genomes of bacteria in a sample but can also include other microorganisms such as viruses and fungi.
There are currently two major high throughput sequencing technologies used to do this; 16S rRNA gene sequencing and whole genome shotgun sequencing (WGS).
16S rRNA gene sequencing was invented by Carl Woese and George Fox and led to the ability to accurately identify the bacteria composing the metagenome of a sample. 16S rRNA gene sequencing depends on amplification of the 16S rRNA gene, which all bacteria have and contains conserved and hypervariable regions. Primer sets are designed to anneal to the conserved regions and amplify the variable regions. In this way, the 16S rRNA gene is amplified from all bacteria and the variable region can be used to identify which specific bacteria is present.
WGS however, does not rely on amplification of a specific gene and instead sequences all genetic material present in a sample. Therefore, this method is not specific to bacteria and will amplify viruses, fungi, protists, and host DNA. Because it does not rely on amplification or specific primer sets, this method is less biased than 16S sequencing. It also allows accurate identification of the organisms down to the species and strain levels along with prediction of their functional capacity based on genes present in the sample.
What is the difference between genomics and metagenomics?
The main difference between genomics and metagenomics is the number of organisms evaluated in an assay or sample. Genomics studies the genome of a single organism while metagenomics studies the collection of different organisms’ genomes within a sample.
What is a metagenome assembled genome?
A metagenome assembled genome, or MAG, is a genome that was constructed from a metagenomic sample. In other words, from a sample containing many genomes, the genomes of individuals are pieced together. MAGs are often useful to shed light on non-culturable, novel, unannotated microbes in metagenomic data.
What makes metagenomic data different from traditional genome sequencing data?
On a broad scale, metagenomic data is produced from the sequencing of many individuals’ genomes simultaneously, whereas traditional genome sequencing data is produced by sequencing one individual’s genome at a time. Practically, this means that communities of bacteria, whether from the environment or living on other organisms, can be sequenced and identified. This is important in elucidating their roles in disease and environmental functions. It can also reveal interactions between organisms living within a community as well as the impact of the environment on the community of organisms. Studying these factors is not possible when examining a single genome.
What are the advantages of metagenome sequencing?
Metagenome sequencing offers many advantages over single genome sequencing. These include:
- Illuminating functional genes, as antimicrobial resistance or virulence genes, present in the community
- Identifying genes involved in metabolic pathways and how they may be changing
- Studying highly diverged microbes, like viruses, or unannotated, novel or unculturable organisms,
- Identifying microbes at strain and sub-strain level resolution,
- Discovering novel taxa, functional pathways and genes,
- Comparing microbial composition and diversity between samples,
- Performing cross-kingdom microbiome analysis, including all domains of life.
Metagenomic sequencing is a recent, cutting edge technology that allows studying all genomes present in a sample. It can identify the microbial composition in a fermented drink or the microbial metabolic functions present in the human gut during disease. Name an environment and metagenomics would capture all genomes present in its sample, even the genomes of organisms which are yet to be discovered by science. Metagenomic sequencing has the potential to produce novel data that help us understand microorganisms on a community level, leading to new discoveries that may enhance everything from healthcare to agriculture to climate science and beyond.