Mapping life

This article is taken from the "Eureka" section of the June 2024 issue of Omalius magazine.

In each of our cells, compacted in the heart of the nucleus, are the chromosomes, the seat of our DNA. DNA is made up of a long chain of molecules, each named A, T, C or G. In all, our genome comprises 3.4 billion of these "letters". By way of comparison, Victor Hugo's river novel Les Misérables has "only" 2.66 million characters, or 1,000 times fewer. And don't be fooled into thinking that our genetic code is the largest in the living world - far from it! The genetic code of corn has 5 billion letters, and that of the Paris japonica flower is 50 times larger than that of a human being.

"And recently, with the evolution of techniques, we can also obtain long sequences, but only a few state-of-the-art laboratories in the world are capable of sequencing a genome in its entirety. Most researchers therefore end up with incomplete genetic codes, fragmented into thousands of pieces. By attempting to preserve the DNA of all European eukaryotes, ERGA will help to considerably improve genome sequencing standards throughout Europe, in order to obtain reference genomes, i.e. of the highest quality."

A Herculean task, given that Europe is home to almost 200,000 species, a fifth of which are threatened with extinction due to global warming and the collapse of biodiversity, among other factors. "It's important to understand that there are many steps involved in obtaining a single genome", adds Alice Dennis. "For each species, you need to obtain quality biological samples, which can be difficult when it's a rare or endangered species. Then comes the genome sequencing and assembly stage, which involves arranging all the DNA fragments obtained. And then we can move on to annotation, before proceeding to analysis."

Annotation, a crucial and "soften neglected" step, is carried out by a committee under the responsibility of the UNamur biologist. "My job is to determine which part of the DNA corresponds to what: such and such a sequence corresponds to a gene, such and such is a regulatory sequence, etc.", Alice Dennis details. "Unfortunately, it's a job that few people know how to do, partly due to the fact that there are few good tools to check the quality of your work."

According to the researcher, the creation of reference genomes will provide invaluable help in preserving biodiversity in Europe. "A single genome provides a great deal of information", she believes. "In most organisms, each chromosome is duplicated. By comparing them, you can already get an idea of an individual's genetic diversity. If this is low, it means that the population is showing signs of inbreeding."

The reference genomes therefore function as Rosetta stones for future studies. "It's much easier and much cheaper to compare a few DNA sequences from many individuals to an original, than to create the latter,"judges Alice Dennis. "This makes it possible to track populations, to identify those that are most at risk. We can also study genes that are subject to strong evolutionary pressures, and likely to mutate over the years."

Beyond Alice Dennis, over 1,000 researchers across Europe are involved in the ERGA project. And the latter is, in fact, the European part of an even larger project, the Earth Biogenome Project, which aims to sequence the entire living world over a 10-year period. ERGA also includes prestigious members such as the Darwin Tree of Life, in the UK, or the ATLASEA project in France, which aims to sequence the DNA of marine life.

But for Alice Dennis, the ERGA initiative goes much further than these major partners: "ERGA places particular emphasis on creating a decentralized network, and a science that aims to be inclusive. These large partners may have the means to sequence any genome, but this would be to the detriment of less well-endowed countries. There are many biodiversity hotspots in Europe to which these large laboratories do not have access. Relying on local expertise, and allowing everyone to participate and develop their skills will ensure that as many species as possible are present in this Atlas. This is also why all the data produced will be available as open access."

After an initial declaration of intent, the researchers behind ERGA set up a pilot project, which closed in 2023, and which removed a number of difficulties. "We tried to coordinate our action even before we received any funding", recalls Alice Dennis. "Each country came with one or two organisms whose DNA they wanted to sequence, and it was all done through a sharing of the resources each had available, and donations from certain companies. This enabled us to identify a number of problems, such as the difficulty of getting samples to travel in good conditions, in order to preserve the genetic material."

All in all, this testing phase has already established 1,213 reference genomes. And the pace is accelerating, thanks in particular to funding from the European Union's Horizon Europe program. The second phase of the project, which starts this year and will run for 5 years, aims to sequence 150,000 genomes, with priority given to the most endangered species.

ERGA is supported by Horizon Europe as part of the Biodiversity, Circular Economy and Environment program (REA.B.3, BGE 101059492).