Small stretches of seemingly useless DNA harbor a big secret, say researchers at the Stanford University School of Medicine. There’s one problem: We don’t know what it is. Although individual laboratory animals appear to live happily when these genetic ciphers are deleted, these snippets have been highly conserved throughout evolution.
“The true function of these regions remains a mystery, but it’s clear that the genome really does need and use them,” said Gill Bejerano, PhD, assistant professor of developmental biology and of computer science. In fact, these so-called “ultraconserved” regions are about 300 times less likely than other regions of the genome to be lost during mammalian evolution, according to research from Bejerano and graduate student Cory McLean.
Although some of the ultraconserved regions, which were first identified by Bejerano in 2004, are involved in the regulation of the expression of neighboring genes, previous research has shown that mice missing each of four regions seem perfectly normal.
“It’s very surprising that none of the four has any observable phenotype,” said Bejerano. “In some ways it just doesn’t make sense.” …
McLean and Bejerano compared the likelihood that ultraconserved elements of at least 100 base pairs shared by humans, macaques and dogs would have been deleted in rats and mice, with the likelihood of a similar pattern in non-conserved DNA. Less than one-tenth of 1 percent of segments completely identical among the primates and dog were missing in the rodents. In contrast, about 25 percent of non-conserved segments were absent in the mice and rats.
It’s not that these regions are somehow protected against change: they are mutated in about one in 200 healthy humans. Rather, these changes seem to be swept away over time by the tides of evolution in a process called “purifying selection.” Bejerano and McLean believe that something similar may be happening in the laboratory mice on a scale too subtle to be seen under carefully controlled experimental conditions. …
“Interestingly,” said Bejerano, “the longer the sequence has been in us, the less likely it is to be lost. It’s almost like the bricks in the foundation of a building, which hold up the rest of the structure.” – scidaily
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