GENE INTERACTIONS IN DOMESTIC X WILDCAT HYBRIDS

This is a short, annotated, summary of findings from Christopher B. Kaelin, Kelly A. McGowan, Anthony D. Hutcherson, John M. Delay, Gregory S. Barsh, "Ancestry dynamics and trait selection in a designer cat breed," December 12, 2022,

An "introgression event" is the incorporation of alleles from one species into the gene pool of a different species through hybridisation and backcrossing. The Bengal was derived from crossing Asian Leopard Cats (ALC) with domestic cats. Fertile female hybrids were crossed to male domestic cats because early generation hybrid males are infertile. The most desirable offspring were selected for breed development. The studbook Bengal was predicted to have 6.25% ALC genes, these being responsible for the distinctive patterns. The researchers found that leopard cat ancestry was about half that expected and was not spread randomly across the genome. It averaged around 3.48%, and the range was 0.46% - 12.3%.

This is what is normally expected, on average.

F1 cross: 50%
F2 backcross: 75%
F3 backcross: 87.5%
F4 backcross 93.75%.

Once the hybrid is 90% one species or the other, the male hybrids are likely to be fertile (based on information from Bengal and Savannah cat breeders).

Each successive backcross after that gives:

96.9%
98.5%,
99.25%
99.6%
99.8%
99.9%

[Note: higher percentages are seen after backcrossing a Bengal to ALC to deliberately increase the percentage of ALC blood. These are then backcrossed to male domestic cats in the usual way.]

The reduced leopard cat ancestry was not due to selection against regions of the leopard cat genome or to dilution of leopard cat ancestry by undocumented crossings to domestic cats. No leopard cat alleles are present at high frequencies in Bengal cats. Instead, there is evidence of selective breeding removing various domestic cat gene sequences (i.e. breeders eliminating undesirable traits).

[Note: When repeatedly breeding Bengals together, we would expect stretches of DNA to be broken up as genes are randomly shuffled and passed on to the offspring. Over several generations, there should be fewer long stretches of DNA from a single ancestor. This would spread various ALC genes around the hybrid cat's genome. Where there are relatively few foundation animals some genes become over-represented in the breed due to genetic isolation. Breeders selected cats with the best patterns (and good temperament) as the parents of the next generation. In doing so, they selected against a number of domestic cat traits - certain colours were undesirable, particularly the red gene and white markings. It was harder to remove some of the dilution factors or colourpoint. There was selection in favour of spotted, rosetted and marbled patterns - horizontally aligned, not vertically aligned as in domestic cats.]

The researchers expected the number of haplotypes (stretches of DNA, with several alleles, inherited together from a single parent) to increase and their length to decrease as Bengal cats were bred together i.e., they expected the stretches of chromosome to be broken up so that ALC genes were spread about the genome. Many leopard cat haplotypes evidence of genetic bottlenecks. This could occur during breed development and/or during selection for specific leopard cat haplotypes. Some areas of the genome appeared rich in ALC genes which suggested that selection and/or genetic drift played important roles. There did not seem to be strong selection for any single locus (such as selecting for a known Mendelian trait) so it could be due to genetic drift. Low fertility and small litter size in early generation hybrids would create genetic bottlenecks. ALC haplotypes from exceptionally fertile hybrids or from those with very desirable traits will be overrepresented in the breed, regardless of selective breeding.

Most domestic cats breeds contain low genetic diversity due to selection for specific traits. The Bengal is more diverse because most foundation domestic cats were randombred. This means there has been positive selection of domestic cat alleles that are now unique to the Bengal breed (or to the Bengal and derivative breeds).

No leopard cat alleles are present at high frequencies in Bengal cats. Instead, there is evidence of selective breeding removing various domestic cat gene sequences (i.e. breeders eliminating undesirable traits).

Leopard cat introgressions at Asip and a second gene, Corin, contribute to the wide range of coat colour from grey-brown to red-orange. [Note: The domestic cat orange gene was not included in the Bengal breed, therefore, the orange-toned "sorrel" cats had to be due to a different gene. That different gene could either have come from ALCs or from domestic cats and its frequency increased by selective breeding, or interaction between ALC and domestic genes.]

INCOMPATIBILITIES

Serious gene incompatibilities result in non-viable offspring or serious defects, but lesser incompatibilities may have cosmetic effects. The Bengal Charcoal colour is caused by incompatibility between the leopard cat Agouti Signaling Protein (Asip) gene and the predominantly domestic cat genome.

Charcoal is a form of partial melanism/abundism that darkens the back, giving the appearance of a black cape along the back and a zorro mask on the face. Approximately 5% of registered Bengal cats are charcoal. The candidate Agouti Signalling Protein (Asip) gene was previously associated with Charcoal in Bengal cats. Five out of 38 charcoal Bengals studied were homozygous for ALC Asip; 27 heterozygous for ALC-derived Asip allele + a domestic cat non-agouti allele (Asipa). Homozygous Asipa caused complete melanism (self black) in normally black-marked Bengals. [Note: in cats with other marking colours, homozygous Asipa causes the corresponding self colour).

Charcoal appears to be caused by reduced expression of a normal leopard cat Asip gene in a domestic cat background. There are 5 distinct ALC Asip haplotypes in the Bengal, each of which can cause charcoal. Each haplotype comes from an independent introgression event from a different ancestral leopard cat chromosome.
The charcoal phenotype has never been reported in the ALC, even if they are homozygous for the mutation.
AsipPb - Asip from leopard cat
AsipFc - Asip from domestic cat
Asipa - domestic cat non-agouti gene (the "self colour" gene when homozygous)
Melanocortin 1 receptor (Mc1r) encodes the receptor for Asip.
AsipPb/Asipa (i.e. heterozygous) gave charcoal.

Researchers found that a Bengal with the ALC version of Mc1r had the same charcoal pattern as a sibling with the domestic cat version of Mc1r. The presence of absence of ALC-Mc1r did not affect the charcoal pattern.

In heterozygous AsipFc/AsipPb cats there was reduced expression of the AsipPb allele, probably due to a mismatch between domestic cat transcription factors and ALC regulatory elements. Gene regulatory incompatibilities may contribute to selection against other ALC-derived genes in the Bengal cat genome.

MESSYBEAST SMALL CAT HYBRIDS

 

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