Inbreeding's Downside Is Not All in the Genes

The Habsburgs learned about inbreeding the hard way. Centuries of marriages between close relatives in this Austrian-Spanish royal family led to mental illness, infertility, and the eventual extinction of the entire bloodline. For more than a hundred years, scientists have chalked up such problems to rare genetic mutations, which come to the fore only when related individuals breed. But a new study in plants indicates that it's not just genes that lead to this so-called inbreeding depression; it's also how these genes are switched on and off.

Philippine Vergeer happened upon the discovery while working with the Scabiosa columbaria plant. Vergeer, currently a postdoc at Radboud University in Nijmegen, the Netherlands, noticed that inbred members of the species—which is native to Europe and Asia and has dark green leaves topped with small, delicate purple flowers—had very different responses to environmental conditions than plants that had not been crossed with close relatives. Drought and poor soil tended to kill the inbred plants quickly, for example, whereas the outbred plants were hardier.

Vergeer could have chalked it all up to harmful rare genes. But then she thought more about the environmental conditions. Drought and poor nutrition are known to cause so-called epigenetic changes to DNA, the addition or removal of small chemical tags known as methyl groups that effectively turn genes on or off. Could such modifications be causing inbreeding depression?

To find out, Vergeer and colleagues counted the methyl groups in the genomes of inbred and outbred S. columbaria. The inbred plants showed a variety of health problems, including difficulty photosynthesizing and slow maturation. They also had 10% more methyl groups in their genomes than did outbred plants, indicating significant epigenetic changes.

To show that methylation was a cause rather than an effect of inbreeding depression, the researchers treated another batch of inbred Scabiosa with a chemical called 5-azacytidine, which removes methyl groups from DNA. Inbred plants treated with the chemical had DNA methylation levels roughly equal to their outbred peers. They were just as efficient at photosynthesis as were outbred plants and grew and matured at the same rate, the team reports online today in Biology Letters.

This is the first time that epigenetics has been shown to play a role in inbreeding depression, says Oliver Bossdorf, an evolutionary ecologist at the University of Bern in Switzerland, and it's significant because it provides an alternate explanation for a phenomenon that scientists had thought they had cracked. "This was really a surprising result. I couldn't have guessed it," he says. "It changes our fundamental understanding of inbreeding depression."

The scientists still don't understand how epigenetics can cause inbreeding depression. Vergeer speculates that the abnormal methylation might result from some of the rare genes exposed by inbreeding, especially if these genes help regulate the attachment and removal of methyl groups. To uncover the relation to inbreeding depression, Vergeer and colleagues intend to probe the epigenetic effects in more detail by determining which genes contain abnormal methyl groups, and where on the gene these groups are attached. Bossdorf says that assessing epigenetics by simply counting total methyl groups is a rather blunt measurement, which Vergeer acknowledges.

Vergeer also notes that these results could be of particular importance to conservation biologists. Loss of habitat to climate change, deforestation, and other human activities have fragmented many species, separating them into small groups. The inbreeding depression that can result from these events can push a threatened species into extinction. "These inbred populations have to respond to changes in the environment, and epigenetics will play a major role in how they do this," Vergeer says.

The findings also indicate that it may one day be possible to treat the deleterious effects of inbreeding with 5-azacytidine or a related compound, although this hasn't yet been tested.

Posted in Biology