Meta­ge­n­om­ics

What is meta­ge­n­om­ics?

Ima­gine a pile of beau­ti­ful books in front of you. Now ima­gine they have been cut into small snip­pets, each con­tain­ing in­di­vidual words and sen­tence frag­ments. You are now given the task of bring­ing or­der to this chaos. The best way to start would be to search for keywords. If the snip­pet says "Ham­let", it prob­ably be­longs to Shakespeare’s work of the same name. And if "new speak" or "Big Brother" comes up, you’re prob­ably deal­ing with George Or­well’s 1984. "Muggles" and "Hog­warts" would clearly point to the Harry Pot­ter series. In this way, you can dig through the pile of pa­per, piece by piece, and try to sort and re­as­semble the snip­pets. If sev­eral cop­ies of the same book have been cut up dif­fer­ently, this makes things a bit easier. Over­lap­ping text frag­ments will give you ad­di­tional clues as to the cor­rect com­pos­i­tion of the texts.

Meta­ge­n­om­ics is­n’t all that dif­fer­ent. In­stead of books, re­search­ers work with the gen­omes of mi­cro-or­gan­isms that they cut up and re­as­semble. The snip­pets are frag­ments of the gen­ome or "se­quence seg­ments". Com­puters can help to as­semble the in­di­vidual parts. There are now ex­cel­lent al­gorithms for deal­ing with such a task. Some se­quence seg­ments are also already known and stored in data­bases. These can help to as­sign cer­tain se­quences to groups of or­gan­isms or func­tions.

With the help of meta­ge­n­om­ics, it is pos­sible to ana­lyse an en­vir­on­mental sample (i.e. a mix­ture of the most di­verse or­gan­isms as they live to­gether in the en­vir­on­ment) and find out which or­gan­isms live in this en­vir­on­ment as well as which genes – and thus meta­bolic path­ways, in­ter­ac­tions, and de­fence strategies – pre­dom­in­ate. This dis­tin­guishes meta-ge­n­om­ics from clas­sical mi­cro­bi­o­lo­gical meth­ods, which spe­cific­ally search for in­di­vidual or­gan­isms (groups) for which the gen­ome se­quences are known. Bioin­form­at­ics refers to the meth­ods used to bring or­der to the meta­ge­n­omic ana­lyses and data.

Meta­ge­n­omic meth­ods also al­low us to identify mi­croor­gan­isms – re­gard­less of whether they can be cul­tured in the labor­at­ory – and thus to study the dy­nam­ics in pop­u­la­tions over days and even years. We can thus gain in­sight into the com­plex­ity and change of the com­munit­ies our mi­cro­scopic co-in­hab­it­ants. However, meta­ge­n­om­ics of­ten can­not stand alone; without clas­sical mi­cro­bi­o­logy, we would be un­able to in­ter­pret the res­ults.

How do we carry out a meta­ge­n­omic ana­lysis?

(© Max Planck Institute for Marine Microbiology, A. Esken)
Explanation in the text (© Max Planck Institute for Marine Microbiology, A. Esken)

In an en­vir­on­mental sample, we find a mix­ture of the gen­omes of vari­ous or­gan­isms, the meta­gen­ome. In or­der to ef­fi­ciently se­quence the meta-gen­ome of a bac­terial com­munity, for ex­ample, we must first dis­as­semble the in­di­vidual gen­omes into count­less frag­ments. Se­quen­cing provides us with nu­mer­ous un­ordered se­quence seg­ments (de­pend­ing on the tech­no­logy used) ran­ging from 100 to hun­dreds of thou­sands of bases in length.

Des­pite the enorm­ous pro­gress in read lengths, the frag­ments are much shorter than the typ­ical gen­omes of mi­croor­gan­isms. The pieces must then be as­sembled into lar­ger frag­ments or "con­tigs", which are con­tigu­ous sets of over­lap­ping pieces of DNA that come from the same ge­netic source – in our case, the same spe­cies of bac­teria. These range in length from sev­eral ki­lo­b­ases to one Mega­base and are thus long enough to be sor­ted sens­ibly.

We can then group the con­tigs in such a way that they yield more or less com­plete gen­omes of in­di­vidual bac­terial spe­cies. In this "bin­ning" pro­cess, the con­tigs are grouped into "bins" de­pend­ing on their base se­quence and fre­quency. A bin is where pieces of the large meta-ge­n­omic puzzle that are most likely to come from a cer­tain bac­terial spe­cies are sor­ted. Once they are suf­fi­ciently com­plete, these bins are re­ferred to as meta­gen­ome as­sembled gen­omes (MAGs).

The graphic visu­al­izes the prin­ciple.

Meta­ge­n­om­ics in ac­tion

The molecular ecology of algal blooms

For ex­ample, we use meta-ge­n­om­ics to study the de­grad­a­tion of algal blooms in the North Sea: every year in spring, when the days get longer and the sun­light in­creases, many phyto­plank­ton spe­cies mul­tiply rap­idly – and their pop­u­la­tion grows ex­po­nen­tially. These algal blooms are of global im­port­ance for the car­bon cycle. Dur­ing pho­to­syn­thesis, the small al­gae con­vert car­bon di­ox­ide into sugar com­pounds and oxy­gen. Within a few weeks, the al­gae run out of nu­tri­ents, and pred­at­ors spread. The al­gae bloom then col­lapses. The bac­teria then mul­tiply en masse. They de­com­pose the re­main­ing algal bio­mass, and the bound car­bon is largely re­leased in the pro­cess. However, these pro­cesses are still not well un­der­stood. Which mar­ine bac­teria grow when? How do they pro­cess the algal bio­mass and re­lease the car­bon? What pro­cesses are be­hind this?

Ex­ample Pro­jects

Sim­pler than ex­pec­ted: A mi­cro­bial com­munity with re­duced di­versity cleans up after algal blooms

Al­gae blooms reg­u­larly make for pretty, swirly satel­lite pho­tos of lakes and oceans. They also make the news oc­ca­sion­ally for pois­on­ing fish, people and other an­im­als. What's less fre­quently dis­cussed is the out­size role they play in global car­bon cyc­ling. A re­cent study now re­veals sur­pris­ing facts about car­bon flow in phyto­plank­ton blooms. Un­ex­pec­tedly few bac­terial clades with a re­stric­ted set of genes are re­spons­ible for a ma­jor part of the de­grad­a­tion of algal sug­ars.

Here you can find the press re­lease: https://www.mpi-bremen.de/en/Simpler-than-expected-A-microbial-community-with-reduced-diversity-cleans-up-after-algal-blooms.html

Heligoland is Germany’s only true offshore island, famous for its seabirds, seals and duty-free shopping rather than for microscopic algae. But what the MPI-scientists were interested in was the fate of the organic matter once the algae die. (© Max Planck Institute for Marine Microbiology, N. Esken)
Heligoland is Germany’s only true offshore island, famous for its seabirds, seals and duty-free shopping rather than for microscopic algae. But what the MPI-scientists were interested in was the fate of the organic matter once the algae die. (© Max Planck Institute for Marine Microbiology, N. Esken)

Lost at sea: Far off the coast, Thio­glo­bus per­ditus lives off its re­serve pack

SUP05 bac­teria are of­ten found in places where there is really no basis for life for them. Re­search­ers in Bre­men have now dis­covered that they are even quite act­ive there – pos­sibly with con­sequences for the global ni­tro­gen cycle. The bac­teria travel with a “re­serve pack”. In ad­di­tion, the re­search­ers have de­ciphered the bac­teri­a’s gen­ome. The res­ults have now been pub­lished in the journal Nature Com­mu­nic­a­tions.

Here you can find the press re­lease: https://www.mpi-bremen.de/en/Lost-at-sea-Far-off-the-coast-Thioglobus-perditus-lives-off-its-reserve-pack.html

Launch of a glider off the coast of Peru. (Photo: A. Reichel, GEOMAR)
Launch of a glider off the coast of Peru. (Photo: A. Reichel, GEOMAR)

Many cooks don't spoil the broth: Man­i­fold sym­bionts pre­pare their host for any even­tu­al­ity

Deep-sea mus­sels, which co­oper­ate with sym­bi­otic bac­teria for their food, har­bor a sur­pris­ingly high di­versity of these bac­terial “cooks”: Up to 16 dif­fer­ent bac­terial strains live in the mus­sel's gills, each with its own abil­it­ies and strengths. Thanks to this di­versity of sym­bi­otic bac­terial part­ners, the mus­sel is pre­pared for all even­tu­al­it­ies. The mus­sel bundles up an all-round care­free pack­age, a Ger­man-Aus­trian re­search team around Re­becca An­sorge and Nicole Du­bilier from the Max-Planck-In­sti­tute for Mar­ine Mi­cro­bi­o­logy in Bre­men and Jill­ian Petersen from the Uni­versity of Vi­enna now re­ports in Nature Mi­cro­bi­o­logy.

Here you can find the press re­lease: https://www.mpi-bremen.de/en/Many-cooks-don-t-spoil-the-broth-Manifold-symbionts-prepare-their-host-for-any-eventuality..html

Rebecca Ansorge and technician Silke Wetzel collect specimen of Bathymodiolus-mussels that were retrieved from the deep with the submersible MARUM-QUEST. (© Max Planck Institut for Marine Mikrobiology, C. Borowski)
Rebecca Ansorge and technician Silke Wetzel collect specimen of Bathymodiolus-mussels that were retrieved from the deep with the submersible MARUM-QUEST. (© Max Planck Institut for Marine Mikrobiology, C. Borowski)
 
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