Metabolomics: The missing link in genetic selection

varian nuclear magnetic resonance (NMR) spectroscopy

Metabolomic selection can improve genetic gain in difficult-to-measure traits by combining whole-metabolomic data with phenotypic, pedigree, and genomic data. The metabolome is the complete set of metabolites in a sample and forms a link in the chain between DNA and phenotype.

By Helle Palmø, Chief Geneticist, DanBred

 

New breeding technologies such as genomic selection, whole-genome sequencing, optimal contribution selection, and gene editing are developing at an increasing pace. Metabolomic selection is an emerging breeding technology based on an exciting new source of information, namely nuclear magnetic resonance (or NMR) metabolomics.

NMR metabolomics measures all metabolites in a sample from an individual. This complete set of metabolites – referred to as whole-metabolomic data – is associated with the level of physiological activity in biological pathways that are initiated at DNA level and culminate in trait expression. The level of physiological activity is, in turn, regulated by the genes that an individual has inherited from its parents, as well as by cues from its environment. This link between whole-metabolomic data and inherited genes may be exploited to increase the genetic potential for desirable phenotypic traits such as feed efficiency and meat quality in pigs.

 

More accurate selection and higher genetic gain

Selective breeding increases the genetic potential of pigs by choosing genetically superior selection candidates as parents of the next generation. The resulting increase in genetic potential, i.e. the genetic gain, is a direct result of the accuracy by which we can predict the breeding values of selection candidates in each generation. The more accurate the breeding values, the higher the probability that we will select the genetically superior candidates and, thereby, achieve a higher genetic gain.

Unfortunately, the accuracy of breeding values is low for the majority of traits in pigs, as also seen in other species. The range is between 10-40 % for most traits, which highlights that we are only realizing a small proportion of the genetic gain that is theoretically possible. The main reason is that the information currently used to predict breeding values – phenotypic, pedigree, and genomic data – does not adequately describe the genetic potential of the pigs. Other sources of information are clearly needed, and this is where whole-metabolomic data comes into play.

 

Increasing genetic gain for feed efficiency

Previous research suggests that metabolomic selection can increase genetic gain. For feed efficiency in pigs, possibly by as much as 25 %. Feed efficiency is an evident trait for which whole-metabolomic data may contribute information that has not yet been exploited due to the expense and difficulty in taking accurate measurements at the individual level. In fact, most pig breeding programs do not record phenotypic feed efficiency information for all selection candidates.

 

Potential benefits for meat quality

Achieving genetic gain for difficult-to-measure traits is challenging because without accurate phenotypes, the genetic potential of individual animals cannot be estimated for those traits. Metabolomic selection may also be of particular benefit for other difficult-to-measure traits such as meat quality, as this is difficult to measure in live selection candidates, and information is typically only available from full- or half-sibs that have been slaughtered.

 

A pioneering joint research project

The DanBred breeding program is the Danish pig breeding program with a long and solid history of developing and implementing the newest sophisticated breeding technology. For example, genomic selection, including DNA-testing of all breeding candidates, has been an integral part of the DanBred breeding program since 2010. Now, DanBred aspires to set the pace for a new and pioneering form of selection with a new innovative research project on metabolomic selection in pigs and barley, which was kicked-off in January 2020.

The research project aims to develop new methods to exploit metabolomics for genetic gain and to evaluate the potential for metabolomic selection in pigs through collaboration with the Danish Pig Research Centre (DPRC), Nordic Seed, and Aarhus University (AU). DanBred specifically aims to increase genetic gain for feed efficiency and meat quality.

The project is partially funded with € 1.1 million presented by the Green Development and Demonstration Program from the Ministry of Environment and Food in Denmark.

“We are very excited about this chance to unravel the genetics of our pigs’ full metabolomic profiles. This will allow us to target the selection for traits in the breeding goal more accurately and increase genetic gain,” Tage Ostersen, Department Manager at DPRC, says.

 

Improved feed efficiency and reduced CO2 emission

The additional predicted improvements in feed efficiency and progressive reduction in feed intake will also lead to reduced CO2 emission. This, as with all effects of genetic selection, will be permanent and cumulative across generations – and this will, naturally, be profitable for pig producers.

“The effects of metabolomic selection will steadily emerge. Our calculations show that by 2050, the feed-to-growth ratio will be reduced by approximately 0.3 kg feed per kg growth – on top of what would be expected when metabolomic selection is not taken into consideration. This corresponds to a cost-reduction of approximately €5.40 per pig and a yearly reduction in CO2 emissions corresponding to 150,000 ton CO2 equivalents,” Tage Ostersen explains.

 

Meat quality to benefit consumers

The quality of the pork meat is an important aspect for the consumer, and meat quality is therefore also an integral part of the project. For example, DanBred plans to measure the level of intramuscular fat.

“Meat quality is traditionally measured in slaughtered animals, which restricts the possibility of measuring phenotypes from a large number of breeding candidates. We expect that metabolomic selection will contribute essential new knowledge about meat quality in DanBred Duroc, which is in high demand, particularly in Southern Europe. Moreover, it will enable targeted products for markets that have a preference for pork with a specific meat quality,” says Helle Palmø, Chief Geneticist at DanBred.

 

What is whole-metabolomic data?

Whole-metabolomic data – also called the metabolome – is the full collection or network of metabolites identified at a certain time in a specific tissue or blood sample from an individual. Metabolites are the small molecules that result from metabolic reactions within the body and reflect physiological activity.

 

How is whole-metabolomic data measured?

Whole-metabolomic data can be measured on a large scale using nuclear magnetic resonance (NMR) spectroscopy. The NMR measurement can be made based on e.g. blood samples from pigs.

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