Cat domestication, parasite ecology, human genetics

So, you’re back from Thanksgiving, and it’s only a few weeks until the winter holidays. Now that you’ve exhausted your arsenal of conversation starters with all that Thanksgiving socializing, you’ll need to restock before you go back for round two. [Enter Messenger].

Phylogenomics of the housecat: My winter holidays involve sitting next to a woodstove with a cat in my lap, watching snow coming down on the backyard. Cats have been part of the human household since about 9,500 years ago in the Middle East, where they were attracted to the rodent-infested grain stores of early farming societies. The cats with more social and less aggressive dispositions were accepted and incorporated into the human lifestyle, ultimately resulting in their “self-domestication,” or the selection for more domesticated varieties based on mutual benefit rather than selective breeding.

However, “little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors,” wrote M.J. Montague, G. Li et al., in the November issue of PNAS (Early Edition). Conducting a comparative analysis of 22 housecat and four wildcat genomes, they found selection for genes involved in neural crest formation, learning and memory—including multiple glutamate receptors and the netrin receptor. In mouse models, genetic knockouts of these genes result in impaired reward response learning, supporting the idea that improved learning capacity was a selected trait during cat domestication. The authors also identified alterations in lipid metabolic pathways that likely allowed cats to adapt to a “hyper-carnivorous diet.”

In the July 2014 issue of Genetics, A.S. Wilkins, R.W. Wrangham and W.T. Fitch proposed the hypothesis that mild impairments in neural crest development could explain the various traits observed repeatedly across different domesticated animals—something that originally puzzled Charles Darwin. For example, slower neural crest migration results in decreased size and function of neural crest-derived organs. The adrenal gland, which is responsible for the fight-or-flight hormone response, is smaller in domesticated animals. Decreased fear and stress responses allow domesticated animals to learn to live alongside humans.

What’s the major difference between cats and dogs? Cat domestication is both more recent and less intense: humans have been domesticating dogs for 30,000 years, while cats entered our lives only 9,500 years ago. For all you dog people out there, that’s more than 20,000 years of breeding to catch up on—cut the cat some slack.

References: PNAS, Science News, Genetics

Parasite ecology: I recently had the pleasure of attending the UCSF Women in Life Sciences seminar, in which Kelly Weinersmith spoke about her dissertation work on fish parasites at UC Davis. When we think of ecological systems, we typically think of the “food web” relationships we first learned about in elementary school science class. Organisms sharing a habitat can be linked not only by eating each other, but also by symbiotic and parasitic relationships. In some cases, parasites can even alter their host’s behavior patterns, which can shift the other relationships in the ecological system.

In an article in the November issue of Conservation Biology (Early View), environmental historian Dolly Jørgensen discusses the importance of remembering parasites when working to preserve biodiversity. When animals were lost from their natural environments and bred in captivity for the purpose of re-introduction in the early 20th century, handling procedures did not include parasite removal. Parasites such as the Beaver Beetle, Chewing Louse and Skin Mite were thus maintained in captivity and subsequently re-introduced in Europe along with their hosts, the beaver and bison.

Today, breeding animals in captivity involves much cleaner handling procedures. When the California Condor became endangered, conservation ecologists bred them in captivity, removing a species of louse found only on these birds. While the re-introduction of the condor has been hailed as a success, it is in fact a qualified success because in the process this louse became extinct. Dolly writes: “Biodiversity conservation needs to account not only for the large fauna most often targeted by reintroduction and other translocation projects, but also for the small fauna along for the ride.” I guess the true ecologist must appreciate the creepy-crawlies in addition to the cute-and-fuzzies.

References: Conservation Biology, Slate

Human Genetics: Lately, there have been too many genetics-related news headlines to keep up with. In a November 2014 issue of Cell, J.K. Goodrich et al. conducted a large-scale twin study and found that identical twins tend to have more similar gut bacterial composition than fraternal twins. Since identical twins have identical DNA, this implies that “human genetics shape the gut microbiome” (the title of their paper). They also discovered that the most heritable bacterial family was Christensenellaceae, which acts as a hub in a network of co-occurring species. Interestingly, these bacteria also correlated with a lower body mass index and, in fecal transplant mouse models, caused reduced weight and fat gain. But the definitive implication of genetics in a phenomenon is just the beginning; the burning question is which gene(s) is responsible for enriching this “lean microbiome,” and even more importantly, how? It’s easy to imagine how the answers to these questions might lead to treatments for metabolic disorders and obesity. 

The search for genetic clues for novel drug development has been embraced by Regeneron Pharmaceuticals. They are building a database of “human knockouts”—people missing a particular gene—that can inform on the efficacy and toxicity of using drugs to block certain gene products from functioning. This approach worked successfully in their development of alirocumab, a monoclonal antibody that inhibits PCSK9 in order to lower cholesterol: People with loss-of-function mutations in PCSK9 had low cholesterol levels but were otherwise healthy, and the anti-PCSK9 therapy has been effective in a blockbuster drug race between pharmaceutical companies (though the FDA is closely monitoring some neurocognitive side effects). 

The search for more healthy people who happen to be missing a gene could identify new potentially safe drug targets for various diseases (if those people can live without it, so can others, right?) —of course there’s the caveat that those human knockouts have lived with the missing gene all their life, and have had a chance to adapt. Nonetheless, it’s an elegant idea that holds a lot of promise; a knockout human, after all, is more clinically relevant than a knockout mouse. 

The “Human Knockout Project” was first described by D.G. MacArthur, a computational biologist at Massachusetts General Hospital, in an Apr. 2012 issue of Science. He is currently working on finding and documenting human knockouts for every gene in the genome (though many will likely not exist, as they will be lethal mutations). Current estimates are that each of us has about 80 single defective copies and 20 double defective copies of various genes. In the words of Osgood Fielding, III from “Some Like It Hot”: “Well, nobody’s perfect!”

Sources: Cell, Science, Technology Review, Reuters, Genomes Unzipped