Inbreeding behind rise in mutational load in horses in recent centuries – study

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The mutational load of horses increased in a sudden burst that began some 250 years ago, with researchers laying the blame on the development of closed studbooks and purebred lines.

The huge drop in the use of draft horses in the 20th century also played a part, driving population collapses in many heavier breeds.

Harmful mutations had bubbled along at a very low frequency for much of the last 3500 years, until the burst in recent centuries, Pablo Librado and Ludovic Orlando reported in the journal Genes.

The researchers, with Paul Sabatier University in France, said domestication changed the evolutionary path of horses by favoring the reproduction of a limited number of animals with traits of interest.

Breeders, they said, had controlled equine reproduction for hundreds of generations. Their decisions had given rise to several hundred breeds, showing striking differences.

However, reduced breeding stocks arising from breeding practices hampered the elimination of harmful variants by means of negative selection, ultimately inflating mutational loads.

Ancient genomics have revealed that mutational loads remained steady during most of the domestication history until a sudden burst some 250 years ago. The pair wanted to learn more about the factors underlying this.

They gathered a dataset consisting of 175 modern horses (comprising 37 breeds) and 153 ancient genomes, all previously published, and explored the harmful mutations.

They confirmed that the burst of harmful mutations in modern times was due to inbreeding.

“This independently happened in multiple breeds, following both the development of closed studs and purebred lines, and the deprecation of horsepower in the 20th century, which brought many draft breeds close to extinction.”

The pair, discussing their findings, noted that recent work by others revealed that the last few centuries have been accompanied by a drop of about 16% in the horse heterozygosity genome-wide, with around a 4% raise in the mutational load within protein-coding regions.

However, the underlying drivers of these shifts had remained unclear, which gave rise to the current study.

“Our findings support inbreeding depression as the main mechanism driving the load burst in domesticates and Przewalski horses.”

They said the load burst cannot be only explained by a higher frequency of harmful mutations, but requires that they increasingly became exposed due to inbreeding.

“The significant correlation between inbreeding and the mutational load identified here further corroborates the role of inbreeding in causing a fitness depression.”

Inbreeding, they said, was caused by two main historical shifts: the advent of closed studbooks, and the rise of steam and combustion vehicles that relegated breeds traditionally used for farming and transport to near oblivion.

Encouragingly, breeders today have the opportunity to leverage genomic information to design mating strategies favoring the purging of harmful mutations from the breeding stock, improving animal welfare and mitigating extinction risks.

Origin and Evolution of Deleterious Mutations in Horses
Ludovic Orlando and Pablo Librado
Genes (Basel). 2019 Sep; 10(9): 649. Published online 2019 Aug 28. doi: 10.3390/genes10090649

The study can be read here.

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