Sire and dam DNA have got to work together

See Part 1 here: https://issuu.com international_thoroughbred/docs/itb_august_2022/s/16516244

SO, UP TO THIS POINT, we’ve established that mitochondria is a part of the genome which exists outside the nucleus of the cell; is transmitted only in direct female line; plays a vital part in producing aerobic energy; and that aerobic energy makes a major contribution to performance even at the shortest distance over which elite thoroughbred compete.

To further confirm the findings that the importance of mitochondria to thoroughbred performance isn’t just speculation, is confirmed in a more recent paper from the Journal of Animal Science.

In a paper entitled “Select skeletal muscle mitochondrial measures in Thoroughbred weanlings are related to race earnings and sire”, Guy, et al found a statistically significant correlation between lifetime earnings and skeletal muscle mitochondrial capacity of thoroughbreds (based on biological samples from the gluteus medius muscle of thoroughbred weanlings).

We’ve mentioned that there are 11 genetically distinct mitochondrial haplogroups found to date in the thoroughbred breed, and 36 subgroups or haplotypes, but we’ve also noted that there isn’t any significant difference in the percentage of elite runners descending from each of these mitochondrial haplotypes.

That being so, what then, causes the differences in mitochondrial measures in the study just mentioned?

Well, there is a clue in the title of the paper, which says “…mitochondrial measures in thoroughbred weanlings are related to race earnings and sire.”

This raises the next question: if the mitochondria are inherited solely in mother-daughter fashion, how does the sire get involved?

It’s thought that mitochondria initially existed as a parasite that evolved a symbiotic relationship with another single celled organism.

Over time, elements of the mitochondria have been absorbed into the nuclear genome and now, for optimal mitochondrial function, it is necessary for the “right”nuclear DNA for the mitochondriaDNA (mtDNA) to be present – basically that there is a crosstalk between the two distinct genomes to achieve the balance of the cellular energy requirements.

As an illustration, in their 2019 paper “Nuclear genetic regulation of the human mitochondrial transcriptome” Ali and colleagues noted that “Genes in the cell nucleus can affect gene expression in the mitochondria, changing the cell’s energy supply” and mentioned that there “..are 64 nuclear loci associated with expression levels of 14 genes encoded in the mitochondrial genome…..implicating genetic mechanisms that act in trans across the two genomes.”

It seems likely that in isolated populations, be they tribes, herds, packs or flocks, the nuclear and mitochondrial DNA evolve together.

For example, two populations of birds known as Townsend’s Warblers, one coastal and one inland, showed differentiated mitochondrial DNA, along with differentiated nuclear DNA, including in regions associated with mitochondrial fatty acid metabolism, demonstrating a simultaneous co-adaptation of nuclear and mitochondrial DNA, in this case in response to climate.

Similarly, but within a single population of bats, a more recent paper found that when comparing bats with near-identical nuclear genetic backgrounds but with contrasting mtDNA, they found significant and tissuespecific effects of mitonuclear mismatch on nuclear gene expression, with the largest effect seen in pectoral muscle of the bat.

It is this simultaneous coadaption of nuclear and mtDNA which tries to ensure the nuclear DNA “fits” the mtDNA, making for optimal mitochondrial function.

In humans, it was found that during maternal offspring mitochondrial transmission, mtDNA inheritance is more likely to match with the nuclear genome ancestry to try to ensure consistency between these two independent genetic systems.

That is, while the nuclear DNA recombines each generation, you get half your nuclear DNA from the sire and half from the dam, generally speaking what is inherited in the nuclear DNA tries as best it can to match the mtDNA and ensure optimal mitochondrial function.

What the nuclear and mtDNA is working against achieving this in racehorses is the human hand, or more specifically the mare owner, and the lack of knowledge that thoroughbred breeders have in knowing what mitochondrial haplotype that their mare has and what stallions best fit this haplotype.

What happens when the nuclear DNA is not as good a “fit” and mitonuclear incompatibilities occur?

Happily, we have examples of that occurrence. Copepods are tiny crustaceans, distant relatives of lobsters and crabs and in one experiment scientists took Copepods from two different tidepools on the California coast – one from San Diego, and a study looking at some from Santa Cruz, nearly 500 miles to the North.

When crossed together, the first generation hybrids were normal, but second generation hybrids were smaller, slowerdeveloping and less fertile.

Crossing the hybrids back with individuals from their own male line did nothing to restore the fitness, but crossing them back with individuals from their own maternal/mitochondrial line did achieve that goal.

A similar, more recent study looked at two subspecies of African cattle – the Bos Zebus (humped) and Bos Taurine (humpless).

DNA analysis shows evidence of extensive interbreeding between the two over 100s of years, but despite this, all African cattle possess the Taurine mtDNA haplotypes, demonstrating an incompatibility between the Zebu nuclear genome.

The next question, of course, is how does this impact the thoroughbred?

As we have said, the thoroughbred has 11 known distinct mitochondrial haplogroups, and they are from roots as diverse as those from which stem such a range of breeds such as the Akhal-Teke, the Arabian, the Syrian, the Shire Horse, the Clydesdale, and in the case of Sadler’s Wells and Nureyev, the Shetland Pony, Icelandic horse and Norwegian Fjord.

Despite this diversity, it appears that the thoroughbred sits somewhere near a mid-point on a continuum in this regard – it’s not a the single breed with the nuclear/ mitochondrial co-adaption mentioned with regard to the isolated populations of Townsend’s Warbler, but its mitochondrial haplogroups have not grown so diverse that they have reached the point of mitochondrial incompatibility, where the nuclear DNA that combines with one haplogroup results in non viability if crossed with another (as with the case of the Bos Zebus and Bos Taurine Cattle).

All of that said, the fact remains, it is far more likely that a horse will have optimum mitochondrial function if his genome contains the nuclear DNA that fits his mtDNA.

In pedigree terms this means when we consider the tail-female line of a mare (representing the mitochondrial line) and then look at the rest of pedigree (representing the nuclear DNA) of an individual or a proposed mating we want to see a structure that indicates that the foal will have a high chance of inheriting nuclear DNA that fits the mitochondrial line of the mare.

We have all looked down at a catalogue page and seen instances where a particular sire or sire-line has had an outweighed influence on the superior runners found in the female lineage noted on the page, but we should note here, that the nuclear DNA can come from either side of the pedigree, which is an important factor when considering matings.