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Deletions of ~510 regulatory genes in humans versus chimpanzees cause humans to lose some traits -- like "bony" penises -- and gain others -- like big brains.  (Source: Gary Wales)

Most primates have spine-filled penises to allow a male to penetrate through dried penis secretions of other males to increase the chance of fertilization when mating with females with multiple partners.  (Source: Philip Reno, Stanford University (left) Bonobos at Arkive.org (right))

The idea that removed regulatory sequences led to increased brain growth in humans was confirmed using testing in transgenic mice (the left embryo has the regulatory sequence removed -- note the blue dye in the brain cortex noting growth).  (Source: Nature/HHMI)
Mankind may have lost spiny penises and whiskers, but it gained far more -- large brains and intelligence

When you look at mankind, for better or worse, we're pretty special.  Arguably no single species has been able to reshape the planet in its image as fully as humans.  So what happened during the course of evolution to make humans so dramatically different in intelligence and abilities from even our closest relatives, say chimpanzees?

That's what a multi-school team set out to answer [press release], with advanced genetic analysis.  The team was led by David Kingsley [profile], a top geneticist at the non-profit Howard Hughes Medical Institute, and included a number of researchers from Stanford University, which is located in Palo Alto, California.

I. The Hunt for Missing Genes

While some find it hard to fathom how a set of small genetic changes could result in dramatically different anatomies -- say growing fins versus arms -- Professor Kingsley has shown in stickleback fish changes to regulatory DNA could have dramatic impact on anatomy and appearance.

Similarly some of the crucial differences between humans and chimps were found to be not actual gene additions or deletions, but rather changes to regulatory DNA.

In total 510 gene sequences can be found in chimps and a variety of other mammal species, but are "surprisingly missing" from humans.  Computer analysis showed that many of these sequence deletions were clustered around steroid hormone genes (which influence sex and anatomy) and neural development genes.

These regulatory changes were thought to grant humans unique traits like bigger brains and erect spines, and cause them to lose other traits such as whiskers and bony penises (more on that later).

But locating potentially important deletions only took the team so far.  They then needed to analyze the deletions.  Describes Professor Kingsley, "We had a team of interested graduate students, postdocs, and developmental biologists poring through this list. It was a fun detective hunt that led to lots of interesting discussions."

II. Penis "Bones" and More -- Intriguing Findings

One inactivation that produced a critical impact in humans was the removal of regulators of the gene GADD45g around neural-specific sequences.  GADD45g triggers cell growth.  So by disabling this regulatory sequence human brains were able to grow larger and more dense, allowing the rich cortex and connecting layers that give rise to intelligence, complex personality, and advanced motor learning.

Other changes revolved around a special sex-specific receptor.

Did you ever stop to wonder why cats and dogs have whiskers and we don't?  Critics of evolutionary theory have long posed such examples.  Well it turns out humans have the genes to potentially grow whisker-like features, but one of the deletions inactivates the growth.

Specifically the deletion is the removal of a regulatory sequence for the androgen receptor, which causes the protein androgen to be produced in that vicinity.  Androgen is responsible for "turning on" male-specific traits.  In this case, knocking out the regulatory sequences knocked out the "on" switch, leaving the genes for whiskers permanently inactivated (barring a rare insertion of an androgen regulatory sequence via future evolution).

A similar male-specific inactivation occurs with the androgen receptor and genes coding for penis bones.

While whiskers may be familiar material, most don't know that chimps and some other mammals actually have "bony" barbs in their penises.  These barbs aren't true bones.  Rather they are made of keratin, the hard material found in human fingernails.

The penis "bones" act as a form of natural male enhancement -- though humans seem to be getting along fine without them.  Gill Bejerano [profile], a developmental biologist at Stanford University in California was responsible for tracking down exactly how humans lost their penile "bones".

Professor Bejerano says we lost our spiny penises approximately 700,000 years ago, around the time humans split from Neanderthals.  A deletion of an androgen receptor regulatory sequence was, once again, to blame.

Increased neural development may have given rise, in part to monogamy, which in turn may have allowed the gene to become non-critical.

Why do chimps and other mammals need bony penises?  In nature, competition is always fierce.  Frequently multiple males try to fertilize the same female over the course of a couple days.  The dried secretions from the first males block entrance to latecomers, in an attempt to increase their chances of being the one to achieve fertilization.

But with a bony penis in hand, such secretory barriers pose little obstacle.  The bony penis is able to break through such obstructions with virtually no damage to the precious male member.

In humans such situations are rare, so sex organs have become simpler.  In other words, because of monogamy we don't need our penises to be spiny any more.

The paper on the changes, including the loss of the penis bones is published [abstract] in the journal Nature, arguably science's most prestigious peer-reviewed journal.

III. The Tip of the Iceberg

Even with a wealth of clues in hand, delving into these mysteries is daunting says Professor Bejerano.  At time the human genome "can be a huge, impenetrable mystery" he says, but, "[Researchers are] beginning to tease out some of the molecular differences that make us human."

A lot more "teasing"/working the data will be necessary if we hope to fully crack that puzzle, though.  The investigation into whiskers, brain development, and penis bones was only the tip of the iceberg.  

Armed with the knowledge of where deleted sequences lie in the human genome, investigators can now perform additional research (one potential target of interest: removed female evolutionary mechanisms dealing with spiny penises) to discover more regulatory differences and how they changed humans and make us look and act far different from our distant monkey relatives.

Outside of scientific interest, learning about how are brains got big and our penises less bony doesn't seem to have a lot of practical applications, but Professor Kingsley explains the methods developed will play a critical role in "solving" the puzzles of genetic-related diseases such as arthritis, cancer, malaria, HIV, Alzheimer's, and Parkinson's (some of which are caused by viruses, but in which genetic dispositions play a major role).

He states, "It's now possible to begin identifying some of the particular molecular changes that contribute to the evolution of human traits. We think that the same sorts of lists and approaches will eventually help illuminate human disease susceptibilities as well. It's a great time to be studying not only where we came from, but also how our genetic history shapes many aspects of current human biology."



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This article is over a month old, voting and posting comments is disabled

By SKiddywinks on 3/10/2011 6:12:03 PM , Rating: 1
Neither of you found the fact that with a simple dose of regulatory sequences, we could give people whiskers?

April Fool's day, here I come.


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