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Losing DNA to become human: bigger brains, smoother penises

We now have a wealth of information in the areas of human genomics and genetics, and we know a bit about some regions of DNA or genes that were subjected to accelerated, recent evolution in the human lineage, however, we still don’t know much about the genotypic basis of many human-specific anatomical, physiological, and behavioral traits. In other words, we do not know precisely what bits of DNA make us human.  A fascinating article was just published by a multidisciplinary team of geneticists and computational biologists, led by David Kingsley of Stanford University in the highly prestigious journal Nature, describing a comparison of chimpanzee and human genomes, that reveled >500 regions of DNA that were lost in humans, but are present in chimpanzees and highly conserved on other primates and other mammals, such as mice.  As usual, simplistically we tend to focus on gains, so we think that we must have some additional DNA, or some radically different DNA sequences that differentiate us from other animals. But sometimes, less is more. It appears that missing DNA sequences can help explain what makes us humans.

There were over 500 regions of DNA missing in our genome that are highly conserved in chimpanzees, ranging in size from tens of kilobases to just a few bases, the average being ~2000 base pairs.  The missing DNA bits seem to be mostly located outside of the coding regions of genes (those regions that direct the production of RNA or proteins), but are preferentially located in regulatory regions, in other words, regions of DNA that turn genes on or off, or that direct their expression in specific tissues, or at specific times during development. This is not surprising, given that small changes in regulatory regions are likely to result in more massive phenotypic changes than simple mutations in genes that may change just one amino acid out of an entire protein.  The relatively new branch of evolutionary developmental biology, or Evo-Devo, for short, is hot in pursuit of the keys to what makes us humans, mice, mice, and flies, flies.

 

One of the regions that called the scientists’ attention was in the regulatory region of the androgen receptor, the protein that interacts with the male hormone testosterone, and mediates its effects. They studied the effects of the chimpanzee and mouse DNA region that is missing in our genome, by introducing these “missing” sequences into transgenic mice and following their expression in these engineered mouse embryos. This DNA region regulating androgen receptor expression determined that the androgen receptor was expressed in vibrissae, the sensory whiskers that all of us recognize in our dogs and cats, and in rodents), and in the genitals of males, resulting in the typical epidermic spikes present in the penises of most mammals, including chimpanzees, but totally absent from the human penis. So now we know that losing this DNAS region around the androgen receptor made us lose our sensory whiskers and smoothen our penises. The authors speculate that the smoother penis makes for very different sex than chimpanzees have, with increased penetration time before ejaculation, which could possibly lead to increased pair bonding, and possible monogamy between human mate partners. The monogamy conclusion seems to be a bit of a stretch to me, but the pair bonding part makes sense: longer, more enjoyable sex acts make for stronger pair bonds.

 

The second missing DNA bit that the scientists studies is in the regulatory region of a gene called GADD45G, which suppresses cell growth. When introduced in transgenic mice, that DNA region directed expression of a marker gene that produces blue color, into the engineered mouse’s forebrain.  If this region is present, the growth-controlling gene is expressed in and the forebrain growth is curtailed.  This strongly suggests that loss of DNA regions in the human lineage could have led to increased brain growth.

 

The authors do not claim to have resolved the quandary of what bits of DNA make us humans, but their two examples of regulatory regions that we lost are a step in the right direction. We now need to take into account not only what gains or changes of DNA have occurred as a result of evolution of the human lineage, but what bits of genetic information we have shed along the path to becoming human.

 

You can read more at Science Daily here. The original Nature article can be found here (may not work without a subscription).

 

[Note: this is my original piece describing the research, I welcome comments: was it interesting? was it clear? did it bore you to tears?, etc. Thanks].

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A guy I worked with killed (murdered) a racoon. In his wierdness he proudly use the racoons penis bone as a tooth pick.

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