Big brains and spineless penises
How DNA deletions may have produced uniquely human traits
Hundreds of deletions in non-coding DNA have helped sculpt human evolution, including an increase in brain size and the loss of sensory whiskers and penis spines, proposes a study published this week in linkurl:Nature.
| The spiny genitalia of the Callosobruchus analis beetle |
linkurl:Wikimedia Commons, Johanna Ronn;http://commons.wikimedia.org/wiki/File:Callosobruchus_analis_penis.jpg
"The molecular basis of becoming human is one of the great problems in biology," said senior author linkurl:David Kingsley;http://kingsley.stanford.edu/ of Stanford University. "There have been suggestions from multiple organisms that changes in non-coding regions were likely to be important," he added, and with the availability of the human genome sequence, "we have an incredibly exciting opportunity to start to address that question."
For over a decade, Kingsley's lab has studied the genetic basis of evolution in stickleback fish, and found time and again that major morphological differences can be tracked to deletions in regions of DNA surrounding key developmental genes. To see if the same was true for human evolution, Kingsley and colleagues compared the human and chimpanzee genomes, identifying 583 human-specific deletions. They then narrowed the list to sequences likely to have an important function by looking for those which are highly conserved across other organisms, including rhesus macaques, mice, and chickens.
"This is a clever thing to do," linkurl:Svante Paabo,;http://www.eva.mpg.de/genetics/ director of the department of genetics at the Max Planck Institute for Evolutionary Anthropology who was not involved in the research, wrote in an email to The Scientist.
"As with many good ideas, it seems almost obvious in hindsight."
The team's final list included 510 DNA deletions, highly conserved across animal species but absent from the human genome. All but one of the deletions mapped to non-protein coding regions, and many were near genes involved in steroid hormone signaling and neural function.
The team closely analyzed two of the deletions and their potential contribution to human evolution. One, a deletion near tumor suppressor gene GADD45G,
may have removed the brakes from cell division and promoted the expansion of brain tissue, contributing to the increase in brain size of humans over other primates. A second, a deletion near the human androgen receptor gene, correlates with the loss of sensory whiskers and penile spines, which mice and other primates still have, but humans (thankfully) lack.
"There's a good chance some of these deletions contributed to the evolution of human traits," wrote linkurl:James Noonan,;http://www.yale.edu/noonanlab/Noonan_Lab/Welcome.html a geneticist at Yale University School of Medicine who was not involved in the research, in an email. Still, the paper's speculations about how the deletions influence brain size or penile spines are "premature," he wrote. "All we know is that these deletions remove regulatory elements; we don't know what that means for human biology yet."
To find out, Kinglsey and his team are now recreating the deletions in mice to see if the removal of corresponding DNA sequences results in neural expansion or the loss of whiskers and penile spines. They will also continue to look at other deletions on the list for involvement in additional human traits. "Just 508 to go," said Kingsley with a laugh.
McLean, C.Y., et al., "Human-specific loss of regulatory DNA and the evolution of human-specific traits," Nature, 471:216-9.
**__Related stories and F1000 evaluations:__***linkurl:Multicellular evolution not linear;http://www.the-scientist.com/news/display/58023/
[22nd February 2011] *linkurl:Minor change, major difference;http://f1000.com/8511965?key=hy8g46s2d2svthm
[22nd February 2011] *linkurl:Evolution loves history;http://www.the-scientist.com/blog/display/54723/
[2nd June 2008] *linkurl: Neanderthal DNA sequenced;http://www.the-scientist.com/news/display/36437/
[15th November 2006]