Using genomics in plant and animal selection

Following the launch of Genethon, an ambitious program for deciphering the human genome, France decided to invest heavily in investigating the genome of plants and, more recently, animals by means of high-budget programs combining public and private research. The first applications are now starting to appear.

In early 1999, France officially launched a plant genomics program when it set up Genoplante. The objective of this large-scale program, which combines public and private research, is to identify genetic information contained in the chromosomes of plants. Planned to last for five years, it has a budget of 220 million Euros. In terms of resources, it is the second largest program in the world after the United States, and easily the largest in Europe.

The objective of the companies involved is to sequence the 22,000 to 35,000 genes of plants, which means identifying each of their constituent base pairs. But their objective is also to obtain a portfolio of patents that protects their discoveries and ensures their independence for the selection and creation of new varieties.

The Genoplante program, which is supported by a network of laboratories across France, first concentrated on two plant models: arabis, a small Arabidopsis crucifer, and rice. It was then extended to four other main crop species for the French market: maize, wheat, oilseed rape and sunflower.

More appropriate selection

Plant breeders can modify characteristics carried by a single gene, and by two or three genes, for example to control the resistance of wheat to a particular disease. But to tackle more complex characteristics such as early maturity or yield capacity, their approach has up to now been much more empirical: they crossed varieties with the greatest potential without really knowing what happened at the time they were crossed. They then studied them in the field, with the results only becoming apparent some years later, when they had obtained sufficient seeds and were able to measure their yield. With genomics, they can target their choice more precisely and obtain results more quickly.

"After the first four years of work, Genoplante has delivered some extremely interesting results," says Michel Debrand, managing director of Biogemma. "We have already succeeded in identifying 300,000 fragments of DNA (EST - Express Sequence Tag) which correspond to a range of 50% to 60% of genes that are expressed in maize, wheat, rice, oilseed rape and sunflower. From this work we were able to produce DNA chips for all the species we are studying."

A DNA chip consists of small samples of DNA bonded in an ordered arrangement onto a support, such as a glass slide for example. Each fragment comes from one of the plant's genes and makes it possible to detect whether the gene is expressed or not, because if it is expressed, the messenger RNA corresponding to this gene can attach itself onto it in a particular way. "These DNA chips are used in the applied programs," explains Biogemma's managing director. "They make it possible to mark genes that react for example to an infestation or a type of stress."

Work on operational genomics, namely being able to associate a function with a gene, is also well under way. "We have, for example, succeeded in 'cutting' the whole of the wheat genome into more than a million DNA fragments which we multiply using bacteria to form BAC (Bacterial Artificial Chromosome) clones," adds Michel Debrand. "This technology makes it possible to isolate interesting genes. For maize the genome is smaller and can therefore be divided into around 100,000 DNA fragments. This makes it possible to pick out from the 25,000 maize genes about 100 genes that for example react to certain diseases."

Tolerance to stress in maize and resistance to insects

In practice, researchers at Genoplante have already succeeded in identifying about a dozen genes that determine tolerance to stress (cold or drought) in maize. They have also identified and located genes that control digestibility of maize and in particular, its lignin content.

They also achieved the quite unexpected discovery of a gene that induces a mechanism for resistance to destructive insects and that can operate in many main crop species. They are also working on resistance to drought stress in plants, disease resistance, the quality of oleaginous crops and cereals (with regard to lipids, starch and proteins), seed growth, yield, etc. In February 2003, Genoplante had already applied for 21 patents.

From these identified gene sequences, new molecular markers have been developed which help plant breeders to create new varieties.

A molecular marker is a marker on the genome that is associated with a characteristic of the plant and that enables the breeder to know if, after a crossing, this characteristic is significantly present in the plant, although not expressed when it grows in the field for example. This is a long-term program, but it is already known that the first varieties arising from this research should appear in seven to eight years' time.

Currently, worldwide, only the genomes for Arabidopsis (120 million base pairs) and rice (400 million base pairs) have been fully sequenced. The maize genome contains 3.5 billion base pairs (a comparable number to the human genome) and that for wheat, 14 billion. But it is apparent that many rice genes are identical to those in wheat and other cereals. This phenomenon, which scientists call 'syntheny', is helpful to their work. It has also been noticed that a large part of plant genomes is inactive.

Researchers at Genoplante are focusing on the part of the genome that is expressed and not on the genome as a whole.

Animal genomes

Following these results for plants, France also decided to set up an extensive program for analysis of the genomes of livestock, the Agenae program (Analysis of the Genomes for Livestock) which began in September 2002. Its objective is to identify and characterise the greatest possible number of genes that govern the main functions of the animal. For INRA, this work should make it possible to control the reproduction, feeding, health and wellbeing of animals and therefore improve herd management, animal product quality and livestock yield.

This program involves public research bodies (INRA and CIRAD) and professional bodies, in particular Apis-Gene which brings together those involved in beef farming in France, and CIPA, the Interprofessional Committee for Aquaculture Products. It runs for five years, will benefit from a budget of 50 million Euros and should involve 120 to 150 researchers at INRA and CIRAD. The scientists will initially concentrate on four livestock animals: cattle, pigs, poultry and fish.