Showing posts with label HUMAN Genome project. Show all posts
Showing posts with label HUMAN Genome project. Show all posts

Wednesday, January 22, 2014

Neanderthal DNA Among Modern Humans? How About the Denisovans' DNA ?



















In a post two years ago, I noted research conducted at the University of Colorado- Boulder, and UC-Denver, that appeared to scotch two common theories: 1) that the Cro-Magnon exterminated the mentally slower Neanderthals, or 2) that they out -competed for resources by higher reproduction rates.   Based on detailed computer modeling, as well as genetic analysis (from the human genome) the research showed instead that Neanderthals were simply absorbed into modern humans. By "absorbed", I mean that their unique phenotype (see image, e.g. for the skull) became non-existent after extensive interbreeding with the modern humans.

Supporting this was the finding  from a year earlier that 1 to 4 percent of modern human genes, mainly in Eurasian peoples, were "leftovers" from Neanderthals. (Evolutionary biologists consider that residual gene percentage the proof of breeding between the two distinct species before the Neanderthals died out roughly 30,000 years ago)    The computer models had been run over 1,500 generations, based on estimated samples of humans and Neanderthals roving across Europe and Asia. One parameter in the model included the researchers' knowledge that the last ice age forced Neanderthals and modern humans to widen their search for food. The computer models showed interaction, but because there were far more Cro-Magnon (something like a 10:1 ratio) over time than the mating- diluted Neanderthals,  until they emerged as just a minor fraction of our DNA.

Since then the proportions, mating frequencies have been more refined. We now know that 2.5 percent of Neanderthal DNA is found in Asians and Europeans. Two Swiss geneticists - Matthias Currat and Laurent Excoffier - researched how much interbreeding would be needed to end up with so little Neanderthal DNA today and concluded it would require one Neanderthal to mate with a human (Cro-Magnon) to create a child every 30 years.

To have been preserved into modern times, clearly the hybrid offspring would have had to have been accepted - but no one can say how they emerged (in what context) in the first place. It might have been by way of rapes during violent battles between humans and Neanderthals or (more benevolently) when Neanderthals were welcomes into one or more human communities.

A new strategy has been adopted by David Reich, in terms of following the directionality of gene flow.  This is made possible given that human females have two X chromosomes and males have one X and one Y. If Neanderthal females mated with male humans more prominently  Reich notes - they'd provide an X- chromosome to all their children. If Neanderthal males predominated in relations with human females they'd impart  an X chromosome to daughters but none to sons.

Reich hypothesizes that if he were to find an unusually low amount of Neanderthal DNA on the X chromosome, say compared to the other chromosomes, it would be a prime clue that Neanderthal males impregnated human females. Conversely, a high ratio would point the other way, i.e. to Neanderthal great-great grandmothers.

Readers may also recall that roughly a year ago, another specimen hominid was unearthed, packed with DNA (which was then sequenced) and found to be not quite human and not quite Neanderthal.  Geneticists concluded the DNA belonged to yet another hominid group hitherto unknown to science and they dubbed it "Denisovan".  Reich and colleagues applied their same methods (as they did to Neanderthal DNA) to the newcomer genome and discovered the genes were closest to Neanderthals  - but the genome also included many mutations not found in either humans or Neanderthals.

Evidently, Denisovans had diverged from the ancestors of Neanderthals somewhat more recently than the split between Neanderthals and modern humans.   Knowing this, Reich and colleagues looked carefully for Denisovan DNA in the genomes of modern humans. They found it in genomes of two populations, one from New Guinea and another from the nearby island of Bougainville. Reich et al found that at least 5 percent of their DNA came from the Denisovans.

By contrast, Reich et al could not find any trace of Denisovan DNA in Africans, or Europeans or mainland Asians.  They did, however, find vestiges in the genomes of Australian Aborigines and in a people known as the Mamanwa in the Philippines.

The picture that's now emerged is that by the time Neanderthals and Denisovans encountered modern humans their genes had been evolving separately for hundreds of thousands of years.  Despite that, it's possible their DNA is still influencing the health of billions today.  Reich, however, is not ready to take a firm stand because the draft genomes of both Denisovans and Neanderthals still have too many gaps and errors to allow for anything more than conjecture.

More research is in the works, including experiments. As Reich puts it, we can actually perform an experiment to decide, say, whether people with a particular chunk of Neanderthal DNA are faster runners than those without it. Just parse the genetic profiles of different people beforehand, turn 'em loose, then draw conclusions after the race. In the same way experiments can be done to determine, say, whether people with a particular chunk of Denisovan DNA are better at logic puzzles .....or more likely to be atheists.

Stay tuned!


Thursday, June 14, 2012

Should the BMI Be Adjusted for Microbiome Mass?

As attention to obesity in this country heats up, and let's bear in mind nearly 12 million citizens have been added to the rolls of the "obese" since the BMI or "body mass index" has been adopted (thereby assuring much more $$$$ for treatments, therapies etc. as imposed by medical practitioners) - one must wonder whether this measure is truly accurate.

Again, to remind readers, BMI is computed thus:

BMI = Wt (lbs.)/  [ht (in)]^2  x 703

The BMI categories which follow from this are designated:

• Underweight = <18.5
• Normal weight = 18.5–24.9

• Overweight = 25–29.9

• Obesity = BMI of 30 or greater

A BMI calculator that can do the computations quickly is at:
 
http://www.nhlbisupport.com/bmi/
 
Now, in my case, given my current weight is 188 lbs. and my height is 5' 6", the calculator shows my BMI = 30.3 or just over the threshold for obese. But is this really an accurate representation? According to the initial findings of the Human MicroBiome Project (a sister to the Human Genome Project) a typical human carries about ten bacterial cells for every human cell.  These 'flora' ride along and are always working - whether to aid in digestion(say in the gut) or to fend off the bacterial bad nasties that are always striving to acquire control - such as clostridium difficilie or 'c. diff.' in the gut - which can occur if a person takes too strong an antibiotic and kills off too many of the beneficial bugs (that neutralize the c. diff.).
 
According to the $173 million project funded by the National Institutes of Health, we each have up to ten trillion bacteria on us and they are not merely passive 'passengers' along for the ride, but 'metabolically active'. We need to see them in the same light as any natural ecosystem, which means if it gets out of balance bad things can occur - whether c. diff. or irritable bowel syndrome, or psoriasis. We need these guys to keep the bad nasties in check, in other words.
 
But here's the deal: given the microbes make up anywhere from 1 to 3 percent of a human's body mass, with the higher percentages going to higher weights (e.g. 3 % is applicable to a person in the 188- 200 lb. wt. class) then that means a 200 lb. person can harbor as much as 6 lbs. of bacteria, according to Dr. Eric Greene, Director of NIH's Human Genome Research Institute.
 
Now, if this is so, then it means that the BMI surely has to be adjusted in order to isolate one's pure (human) body mass from the mass of the non-human organisms ( 'bacteria'). Thus, in my case, if I am carrying about 6 lbs. of these denizens then one would need to correct via subtraction:
 
e.g. Wt.' = Wt. - 6 lbs. = 188 lbs. - 6 lbs. = 182 lbs.
 
And re-calculating the BMI once more (minus the extras) yields:
 
BMI =  Wt'  (lbs.)/ [ht (in)] ^2 x 703  =  182 lbs./ (66 in.)^2 x 703
 
or from the calculator:
 
BMI = 29.4
 
In other words, I instantly transfer from the "obese" category to the simply "overweight. What a difference that such an adjustment can make in the right circumstances!
 
Will the health-medical complex and cognoscenti accept this correction? Likely as not they won't. They will simply argue that the BMI "already accommodates" the bacterial colonies since every human has them- so no need for special adjustment. However, I will stand by my adjusted version! Reason: If the mass of the bacterial bugs constitutes an additional contribution that doesn't specifically belong to me, why include them? Especially if it means the difference between being merely "overweight" and "obese"?