The
Thoroughbred horse population is one of the largest closed populations
of animals in the world. Thoroughbreds are extremely valuable because of
the large amount of prizemoney on offer and the high residual value of
superior athletes. All Thoroughbred horses trace their ancestry back to
three paternal lines, due to the narrow bottleneck at the foundation of
the population https://www.nature.com/articles/s41598-018-24663-x#ref-CR1" rel="nofollow - 1 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR2" rel="nofollow - 2 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR3" rel="nofollow - 3 . More than 300 years of breeding practices have produced signatures of selection in the 21st century Thoroughbred population, contributing to the superior athleticism of the breed https://www.nature.com/articles/s41598-018-24663-x#ref-CR4" rel="nofollow - 4 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR5" rel="nofollow - 5 .
At the same time, these practices have increased levels of inbreeding
and reduced the genetic diversity of Thoroughbreds compared with other
domestic horse breeds https://www.nature.com/articles/s41598-018-24663-x#ref-CR3" rel="nofollow - 3 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR6" rel="nofollow - 6 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR7" rel="nofollow - 7 .
To
our knowledge, there has been no detailed examination of the effects of
inbreeding on the racing performance of Thoroughbred horses and the
genetic load of the population. Genetic load, the presence of
unfavourable genetic material, is a reflection of a population’s fitness
because a higher genetic load leads to a lower mean fitness level https://www.nature.com/articles/s41598-018-24663-x#ref-CR8" rel="nofollow - 8 .
A large proportion of genetic load consists of recessive deleterious
mutations, known as mutational load. Inbreeding can expose mutational
load because it increases an individual’s chance of inheriting two
copies of recessive deleterious alleles from a common ancestor https://www.nature.com/articles/s41598-018-24663-x#ref-CR8" rel="nofollow - 8 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR9" rel="nofollow - 9 .
The subsequent decrease in fitness caused by these expressed recessive
deleterious mutations is thought to be a major cause of inbreeding
depression https://www.nature.com/articles/s41598-018-24663-x#ref-CR10" rel="nofollow - 10 .
Other mechanisms believed to contribute to inbreeding depression
include epistatic interactions and reductions in favourable
heterozygosity https://www.nature.com/articles/s41598-018-24663-x#ref-CR10" rel="nofollow - 10 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR11" rel="nofollow - 11 .
The inevitable effect of selection in a closed population is an increase in the level of inbreeding https://www.nature.com/articles/s41598-018-24663-x#ref-CR12" rel="nofollow - 12 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR13" rel="nofollow - 13 .
There is some evidence that continued inbreeding for selection can
purge a population of some or all of its genetic load, such that new
inbreeding events have negligible or even positive effects on phenotype https://www.nature.com/articles/s41598-018-24663-x#ref-CR9" rel="nofollow - 9 . Although some domestic and wild populations show signs of purging https://www.nature.com/articles/s41598-018-24663-x#ref-CR14" rel="nofollow - 14 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR15" rel="nofollow - 15 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR16" rel="nofollow - 16 , others still show strong signs of inbreeding depression even after multiple population bottlenecks and inbreeding events https://www.nature.com/articles/s41598-018-24663-x#ref-CR17" rel="nofollow - 17 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR18" rel="nofollow - 18 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR19" rel="nofollow - 19 .
Purging is most likely to occur in populations under strong selection
and slow rates of inbreeding, allowing deleterious alleles to be
effectively eliminated rather than fixed by genetic drift https://www.nature.com/articles/s41598-018-24663-x#ref-CR11" rel="nofollow - 11 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR20" rel="nofollow - 20 .
Additionally, inbreeding for favourable phenotypic characteristics can
have unexpected negative implications through deleterious alleles
hitchhiking on regions of the genome under positive selection, thereby
increasing their frequency in the population https://www.nature.com/articles/s41598-018-24663-x#ref-CR21" rel="nofollow - 21 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR22" rel="nofollow - 22 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR23" rel="nofollow - 23 .
Understanding
the effects of selection is further complicated by the uneven
distribution of genetic load in a population. Inbreeding to different
ancestors can have varying effects on fitness, such that the total
proportion of alleles identical by descent (IBD) might not be an
accurate reflection of mutational load https://www.nature.com/articles/s41598-018-24663-x#ref-CR24" rel="nofollow - 24 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR25" rel="nofollow - 25 , https://www.nature.com/articles/s41598-018-24663-x#ref-CR26" rel="nofollow - 26 .
This raises the possibility that inbreeding in different pedigree lines
has variable effects on genetic load in the Thoroughbred population.
The availability of extensive phenotypic and pedigree records, dating back to the late 18th
century, makes the Thoroughbred population ideal for studying the
long-term, population-wide effects of selection on performance and
genetic load. Here, we examine the effects of inbreeding on racing
performance and mutational load in the Australian Thoroughbred
population. Australia has the second-largest racing and breeding
population in the world, containing approximately 15% of all
Thoroughbreds https://www.nature.com/articles/s41598-018-24663-x#ref-CR27" rel="nofollow - 27 .
We
analyse a sample of 135,572 individuals, representing all Thoroughbred
horses that had one or more race starts in Australia between 2000 and
2011. A genealogy of these individuals, dating back to the founders of
the population (n = 257,249), is also included in our analyses.
Although some lines of pedigree are incomplete, we have comprehensive
pedigree information for all individuals in the racing performance data
set, making our inbreeding estimates highly accurate. The availability
of extensive pedigree records not only allows us to study broad
population trends over time, but also to determine whether the selection
for optimal racing performance has alleviated mutational load. We use
these data to measure inbreeding and ancestral coefficients for all
individuals. We also identify the ancestors that have made the greatest
genetic contributions, in order to understand better the distribution of
mutational load in the population. For a representative subset of
individuals, we perform high-density genotyping to determine whether
inbreeding load is reflected at the genomic level.