Domestication – rabbits now catching up with plants

Domestication of species is critical for our farming and own nutrition, as well as being important for retrospective studies of evolutionary genetics and future applications in animal and plant breeding. The genes involved in the first stages of domestication in plants are relatively clear: a single, tasty, energy-rich, product over-produced with a high proportion easily harvested, quick and easy establishment when planted, and disease resistance (free: Special Issue Preface and full issue of Annals of Botany). It has been less clear what is needed from a newly domesticated animal: many are multi-purpose (wool, leather, milk, meat, draught/traction, as well as companions and guarding), but why haven’t more animals been domesticated? What traits are being selected? (In particular, not one of the nearly 1000 sub-Saharan vegetarian mammal species has been domesticated.) Remarkably, most of our current crop plants and animals were domesticated in a relatively short period about 10,000 years ago, so, particularly for animals, finding near-relatives for genetic studies has been difficult.

A new paper from Miguel Carneiro Porto, Portugal, and colleagues from Sweden and the US in Science this week (Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication – Carneiro et al. p. 1074; 29 August, on the Science website) uses genomic analysis of DNA in domestic and wild rabbit with whole-genome DNA sequencing information. They address some of the key questions about animal domestication. Another summary of the paper is given by Penny Sarchet in New Scientist today. Rabbit domestication is recent – only in the last 1400 years; wild populations exist for comparison, and there are multiple selected breeds, so it is a good system to work with compared to other animals. I met first Miguel Carneiro when he talked about a related paper at a meeting in Portugal in 2010 (2011 Mol Biol Evol, The Genetic Structure of Domestic Rabbits Carneiro et al.), but have not had other contact with him, although we have continuing collaboration with a nearby lab Prof Raquel Chaves at Vila Real, Portugal, on bovid genome structure and evolution.

Key points for me from the rabbit paper are that they found about 100 regions that were selected to be different and showed evidence for selective sweeps (genomic regions of reduced variation and segregation distortion or linkage disequilibrium) in the domesticated compared to wild rabbits. This means that many genes were selected simultaneously (new result) so domestication was difficult and involved only a dozen to a thousand individuals (those latter data are in the 2011 Mol Biol Evol paper) with the appropriate combination of genes. This high number also explains why domestication loci have been hard to find in animals – it is too many to study with crosses and genetic analysis, only with genome sequencing (a new result). The second really interesting new point is which genes are in these regions: they find genes affecting brain development and sensory organs are strongly over-represented in these regions. In other words, selection during domestication might have focused on tameness and lack of fear: as a farmer, you neither want the animal to hurt you, nor for the animal to die from stress. Secondarily, an animal uses a lot of energy and time to keep a look-out and flee – energy that humans would rather went into meat and milk! It is notable that gene loss is not significant during evolution: most of the changes are due to gene allele polymorphisms.

I do mention sensory perception, ‘friendliness’ and fear in my lectures on animal domestication – zebras kill more people in zoos than any other animal because they bite and hold on to their keeper, while deer panic and have heart attacks or break a leg. But until now there have been minimal real data about the changes in this group of genes – I think this paper is a first. (I once heard a talk about reduced brain size in farmed trout fish, but forgot the author and never found a reference.) Given the large number of loci, possible introgression and crosses to wild rabbits every few dozen generations (although this was not noted in the study and should have been evident), and large regions around genes affected by the genomic sweep that include non-coding polymorphisms, the results make a lot of sense. They also explain why previous studies have had difficulty in showing genetic signatures of domestication in farmed animals – lots of loci, too long periods to study, more difficult population structures without wild relatives.

I did contact Miguel Carneiro about the introgression question: he replied “there is good solid data that domestic rabbits when released in the wild and in the native range (Iberia and France) are very unlikely to survive the first couple of days due to predation pressure, indicating that introgression in this direction is difficult.” So indeed, the reduced sensory perception and reduced fear response has an immediate and large consequence. He comments that the reverse of wild introgression into domestics is likely to have happened, but the genetic bottleneck signature in domestic rabbits perhaps suggests that this is not so frequent.

Lack of segregation of characters in crosses to look at rabbit (or indeed other animals,where wild x domestic crosses are possible) domestication characters suggests many genes are involved (unlike the small number of genes controlling, say, coat colour in rabbits, or growth-related genes like broiler vs egg-laying chickens). I would speculate that many different monasteries in France in the middle ages tried to keep wild rabbits, eventually with a few finding rare rabbits with a suitable combination of characters which were then progenitors to the current domestic breeds.

The genomic loci give many suggestions where we should look to improve rabbits. I have blogged about the possible importance of aquaculture and fish or crustaceans as a part of improving agricultural sustainability already, but introduction of rabbits as a more exploited source of animal protein also has potential: they (or at least their bacterial gut microbiome) means they digest grasses and fibres. Thus, like cows but unlike pigs or chickens, they can use agricultural products that do not compete with human food uses. Since rabbit domestication is so recent, we can also anticipate what ‘second stage’ domestication traits we should be looking for – rather as we suggested earlier this year should be done in proso millet, Panicum miliaceum, which was domesticated in the first wave but has since declined in relative importance despite having extremely high water efficiency.

What wasn’t found in the the genes associated with rabbit domestication was remarkable. There is no mention of disease-resistance loci and nor of reproduction or breeding-related genes – I would expect these to be over-represented in selected regions (both of which are important traits for domestication of both plants and animals). Disease and reproduction are very important in other domestic animals: high population densities mean diseases spread quickly, while we need fast and easy breeding with no photoperiodic breeding response (not least so we can have eggs and milk all through the year and don’t need to keep cattle until they are 4 or 5 years old before breeding). It is possible these are single-gene loci which would be found but not necessarily stand-out in a genome-wide analysis. Or maybe these are characters where wild rabbits already have the domestication-required genes: they live in large inter-connected colonies (not unlike a farm already) and of course are a byword for reproductive success!

Another summary of the rabbit genomics of domestication paper is given by Penny Sarchet in New Scientist.

Science 29 August 2014:
Vol. 345 no. 6200 pp. 1074-1079
DOI: 10.1126/science.1253714

Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication

Miguel Carneiro, Carl-Johan Rubin, Federica Di Palma, Frank W. Albert, Jessica Alföldi, Alvaro Martinez Barrio, Gerli Pielberg, Nima Rafati, Shumaila Sayyab, Jason Turner-Maier, Shady Younis, Sandra Afonso, Bronwen Aken, Joel M. Alves, Daniel Barrell, Gerard Bolet, Samuel Boucher, Hernán A. Burbano, Rita Campos, Jean L. Chang, Veronique Duranthon, Luca Fontanesi, Hervé Garreau, David Heiman, Jeremy Johnson, Rose G. Mage, Ze Peng, Guillaume Queney, Claire Rogel-Gaillard, Magali Ruffier, Steve Searle, Rafael Villafuerte, Anqi Xiong, Sarah Young, Karin Forsberg-Nilsson, Jeffrey M. Good, Eric S. Lander, Nuno Ferrand, Kerstin Lindblad-Toh, Leif Andersson

ABSTRACT
The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.