The year is 2003. Scientists from 16 laboratories in six countries, USA, UK, France, Germany, Japan and China, assemble the human genome. It culminates a decade of efforts and opens new doors to research. From this scientific milestone important advances in biomedicine have been made, but it has also contributed to the knowledge of human evolution and history.
Today, 9 years later, technological progress has substantially shorten the time and cost of drawing the genetic map of an animal or plant. In fact, researchers around the globe are already analyzing the genomes of different animals and plants. In Spain, six centers of Andalusia, Madrid and Catalonia have come together to assemble the genome of the Iberian lynx, an emblematic species endangered. It will be the first animal sequenced from scratch in our country.
Interestingly, in 2003 human genome assembly coincided with the anniversary of another scientific milestone: 50 years since the discovery of the DNA helix structure. Genetics has allowed scientists to approach the study of the characteristics and processes of life through the analysis of some genes in isolation, while genomics has given way to a new dimension of study covering the whole of the genetic information. Diferences aside, in the case of observing the sky you could say we've been watching the stars with a simple telescope from a rooftop and now we have moved to a powerful observatory installed on top of a hill.
It was therefore a major step to achieve the total picture of the human genetic map, which consists of about 3,000 million nucleotides, or letters of DNA. What scientists call 'sequencing' the genome is precisely to identify each of those letters and their corresponding spaces and put them in place, forming the first words and then a vast encyclopedia which defines the characteristics and evolutionary history of living things.
"Sequencing the genome of the Iberian lynx will allow us to move from looking at 36 anonymous sites in the genome, possibly without function, to cover the entire genome, and to include the information of functional regions. With this, we will be able to investigate the evolutionary history of the species, understand its unique adaptations and assess how the decline has affected the functional variation, for example, genes that are necessary to combat disease, "according to the study coordinator to sequence the genome of the Iberian lynx and responsible group of conservation genetics of the Biological Station of Doñana (CSIC), José Antonio Godoy.
How to order the DNA puzzle
Conservation of Iberian lynx could benefit from this effort, because we will be able to locate regions of the genome related to a defect or disease and take action on the captive population so that reproduction cand be managed to produced healthy offspring and to maintain and even improve the health of new litters
The genome contains instructions for the fucntioning of an individual, whether animal or plant. "It's the whole organism's genetic information. Includes parts that are expressed -genes that play a role, such as generating an enzyme- and others that are not. The estimated number of genes in the human genome is only 20,000 - 25,000, and a mere 2% of the genome actually codes for proteins. A major part of the genome is thus occupied by genes that no longer work, retroviruses and repeated sequences. Many of these sequences do not have a specific function and others must have it, although we do not know which yet,"explained researchers Elena Godoy and Marmesat.
New techniques allow the reading of the genome in relatively short sequences, like short phrases within a huge text, and may contain errors. Having all the text represented and puting the words and phrases in the right order ato reconstruct the original text is a great challenge. As in the case of a huge puzzle, having a reference guide is always useful. The Iberian lynx, the world's most endangered cat, has one: the domestic cat genome that was sequenced in 2007.
Putting pieces together, a detailed task
The lynx Candiles-a male born in 2006 in Andujar and now in the breeding center of Jaen-The Olivilla has been chosen by the Spanish project for the reading and assembly of the Iberian lynx genome.
The basis of all research is a small blood sample from Candiles from which the required DNA was extracted. "We are able to read little chunks of genomes, like short lines of a large text, at random, and we need to make sufficient readings so that each letter appears multiple times in slightly different phrases. These different lines are compared with each other and are assembled to generate a text as long and continuous as possible, "says Godoy.
Thus, each letter of the genome of lynx has been read 80 times so they could be put in place. In Barcelona, the Centre National d'Genomic Analysis (CNAG), directed by Ivo Gut, is responsible for generating the readings and assembling the parts to achieve an orderly whole that can be read continuously, like a novel. Once achieved, "we must interpret the text, find where each chapter begins and ends, and give it a title and a function . This is essential to know where to look next. " This task will be led by Roderic Guigó at the Centre for Genomic Regulation (CRG) in Barcelona, in collaboration with CNAG bioinformatics. Project leaders hope to have sequenced the genome of the lynx and in this year 2012. Scientists call this getting "first annotated draft " ie, having a first genetic map of sufficient quality to be able to start working on it.
This process will not only generate useful information for the species, but also other permanent resources as different gene libraries -collections of pieces of the genome maintained in microorganisms- than will be produced by the Evolutionary Biotechnology group at the Center for Biological Research CSIC, coordinated by Jose Luis Garcia.
Other researchers such as Toni Gabaldon, Center for Genomic Regulation, will use the information generated for comparison with the genomes of other species. Others, such as Thomas Marqués, Institute of Evolutionary Biology, will analyse the variation in repeated sequences, or investigate the genes that might have appeared as novelties in the species, as is the case of Mar Alba, IMIM and the Universitat Pompeu Fabra.
The main aim of this research is to generate the first map of the Iberian lynx genome, which will provide important information on the evolution of this species and on the genetic consequences of its decline.
The lynx genomic sequence has already been identified by CNAG and is in the process of being assembled. When the process ends, in 2012, the researchers will face a new challenge: interpret it and compare it to other felid genomes.