Wednesday, June 15, 2011

Human DNA Migration and How to Extract DNA From a Banana

Nelly Furtado Mash-Up

DNA Mash-Ups

Who do you look like?

Genotypically and phenotypically, which relative (or mailman) do you resemble? Like our DNA, we're mash-up expressions of our ancestral pasts... My Taiwanese relatives tell me I physically resemble my maternal grandmother, yet my youngest sister is an uncanny amalgamation of my paternal grandmother and my dad's older sisters.

Cetus Corp

In Advanced Bio in high school, our prof taught us how to extract DNA using high tech equipment from Cetus (bought out by Chiron, later bought out by Roche) and protocols from Cold Spring Harbor. Funny how technology merges or gets hijacked. My teacher was Mr. D and was the coolest because he gave us the key to the lab (and yes, we goofed around like all seniors).

Science can make indelible impressions, no?

How to Extract DNA 101

Here is a low tech home science project which is incrediblyfun and easy to do. DNA is the language of life -- 4 letters (A T G C) in a pair linked helix translate proteins to organs to life. Extract it from anything (bananas, beans, etc) with a little clear soap (EDTA -- an organic molecule which chelates and sequesters trace and heavy metals). The end step involves swirling the DNA 'snot' onto a glass rod or q-tip.

o Learn Genetics (Univ of Utah) How to Extract DNA From Anything Living
o PBS Nova Extract DNA From a BANANA Recipe (example HERE)
o Scientific American: Find DNA in a BANANA (see picture)

[Great U of Utah resources here: Evolution starts with DNA and Ingredients for evolution: variation, selection and time]

DNA Flow = Gene Flow (e.g. s*xxx)

In 99% of flora and fauna on earth, gene flow is carried forward via the confluence of events known as fertilization by the combination of an egg and sperm. Rare exceptions include slime molds, asexual fungi and 'immaculate conception'.

Researchers can now trace the ancestral carriage of certain genes by examining the frequence of polymorphisms in expressed proteins like ACE, APOE and APOB. APOE (apolipoprotein E) has been particularly interesting to me because of its role in immunity, neurobiology, and lipoprotein/fat/cholesterol metabolism. Modern medicine ignores the role of Apo E and its impact on lab metrics. Many in the paleosphere appear to *LOVE* calculating their LDL using the Iranian formula, however like Friedewald this metric is highly flawed. Not only is the premise for the LDL-heart hypothesis inherently incorrect, humans and other mammalian species do not conform to uniform cookie-cutter lipoprotein patterns.

See prior nephropal: Apo E4, Highest LDL Expression

Human DNA Migration (mtDNA)
Let's return briefly to Douglas Wallace, one of the originators of the mitochondrial medicine model (Wallace DC. Am J Hum Genet. 57:201-223, 1995. Free PDF
). The above diagram traces the path of mtDNA following human migration since leaving Africa over 100,000 years ago. I think it will be quite neat later when they can include mtDNA data from the skeletal remains of neanderthals, H. heidelbergensis and H. erectus, our other ancestors.

Apo E4 = Ancestral Allele

(above diagram, see Luduc et al) Apo E4 not only is associated with higher Triglycerides (TG) and LDL cholesterol, but also aboriginal and ancestral hunter-gatherer societies. It is argued but widely accepted that apo E4 is the ancestral allele associated with the far past tightly evolved from our 200,000 YBP (years before present) to 4 million YBP hominid ancestors. Apo E3 showed up and evolved at least 300,000 year ago (found also in Neanderthals, Luduc et al), however apo E2 has only appeared recently according to scientific estimates. Rarely does any Amerindian culture exhibits apoE2 without obvious agrarian European gene flow.

Climate: Hot and Cold Extremes Selected ApoE4

The recipe for evolution and the excelling domination of a certain characteristic (phenotype/genotype) are: variation, time and selection. An increasing frequency of apoE4 has been witnessed along a south-to-north gradient in Europe (e.g.increasing with cold and fatty acid requirements for thermogenesis BAT). For equatorial cultures, on the other hand, a north-to-south contrasting pattern has been fully elucidated (increasing with heat and salt/mineral requirements with losses in sweat). Eisenberg et al (see below diagrams) hypothesizes that extreme climates which require higher cholesterol requirements and temperature regulation contributed to the higher apoE4 incidence. Agrarian practices appear to have initiated the latest allele appearance, apo E2, which is associated with less carbohydrate toxicity/sensitivities and an apparent buffer to modern SAD chronic conditions (mental, metabolic, autoimmunity).

Apo E4 Global Distribution

Carriers of apoE4 are 'survivors' since the dawn of time. In the medical literature, apo E4 has had a lot of attention because of its association with Alzheimer's, dementia, autoimmune disorders, Western SAD chronic conditions and obesity/metabolic syndrome/T2DM.

Highest allele frequency observed in:
--northern Europe (e.g. my hypothesis, Neanderthal clades)
--northern China (Mongolia, ancestral Han)
--southern India (equatorial)
--Aboriginal/hunter-gatherer subpopulations

Purpose and Role of ApoE4

Apo E has been associated with protection from infectious disease (diarrhea, viral, bacterial) and perhaps survival in select climate extremes (cold/harsh and hot/equatorial). E4 carriers (2/4, 3/4 or 4/4) exhibit heightened absorption of fat-soluble nutrients and cholesterol from the gut. Singh et al describes apoE4 'has also been proved to be a useful marker for evaluation of biological carriers are more responsive to dietary fats and this could be an advantage when food supplies are scarce or irregular. It is associated with better intestinal absorption of lipids including the fat-soluble vitamins A, D, E and K. This may be the reason that APOE E4 appears to be more common in hunters–gatherers than the long-established agricultural communities, e.g. southern Europe, Southeast Asia and Central America (Gerdes et al. 1996a; Corbo and Scacchi 1999) (Singh et al. Annals of Human Biology, 2006).' ApoE4 guards against cholesterol loss and maintains cholesterol homeostasis and cholinergic integrity in the central nervous system (e.g. brain).
In New Zealand, researchers found a correlation between apoE4, heavy metal toxicity and chronic diseases (chronic fatigue, western diseases, heart disease). After chelation of metals, chronic disease status improved. In the ApoE4 protein structure at position 112 (see Luduc diagram above), arginine occupies the site. In E3 and E2 however cysteine has evolved to occupy position 112. Cysteine has advantages in metal dominant environments.

Godfrey et al explain the variance on heavy metal accumulation by the influence of apoE4 v. E3 v. E2, below.
Isomer ε2 has two cysteine
amino-acids in its structure, ε3 has one cysteine and
one arginine, and ε 4 has two arginine amino-acids and
no cysteine [6]. Cysteine, with its sulphydryl (-SH)
bonds, is potentially able to bind to, and remove metals
(e.g., mercury and lead) from tissues, whereas arginine,
lacking the -SH bonds, would be unable to do this.
Apo-E genotyping therefore becomes relevant once it
is acknowledged that prolonged exposure to mercury
has been associated with neurotoxicity, including the
pathological histology unique to Alzheimer’s senile
dementia, namely, fibrillary tangles, amyloid plaques and
increased phosphorylation of tau protein [12,27,28,32].
Conceivably, IMHO, the ancestral allele allowed hominids and mammals to evolve away from rich marine-mineral sources to northern latitudes and above-sea-level altitudes which were physical terrains and landscapes devoid of and lacking brain/body nutrients: minerals (iodine, mag/calcium, zinc), omega-3 and UVB radiation for skin-synthesized vitamin D3. Our DNA mash-ups and heterogeneity explain not only our current health status but can illuminate the path to physiological recovery of neolethal damage and full health optimization.

See prior nephropal: Survival of the PHAT-est


1. Influence of apolipoprotein E genotype on the reliability of the Friedewald formula in the estimation of low-density lipoprotein cholesterol concentrations.
Tremblay AJ, Bergeron J, Gagné JM, Gagné C, Couture P.
Metabolism. 2005 Aug;54(8):1014-9.

** Iranian (for apoE2, inherently low TGs) v. Friedwald (for wildtype apoE3). See resource. **

2. The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Free PDF.
Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csázár A, Utermann G.
Am J Hum Genet. 1991 Aug;49(2):338-49.

3. The effect of apoE genotype and sex on ApoE plasma concentration is determined by dietary fat in healthy subjects. (Email me for PDF)
Moreno JA, Pérez-Jiménez F, Moreno-Luna R, Pérez-Martínez P, Fuentes-Jiménez F, Marín C, Portugal H, Lairon D, López-Miranda J.
Br J Nutr. 2009 Jun;101(12):1745-52.

4. Apolipoprotein E isoform phenotype and LDL subclass response to a reduced-fat diet. Free PDF. [Higher LDL-IVb 'death band' with 'low fat diet']
Dreon DM, Fernstrom HA, Miller B, Krauss RM.
Arterioscler Thromb Vasc Biol. 1995 Jan;15(1):105-11.

5. Carbohydrate intake, serum lipids and apolipoprotein E phenotype show association in children.
Ruottinen S, Rönnemaa T, Niinikoski H, Lagström H, Saarinen M, Pahkala K, Kaitosaari T, Viikari J, Simell O.
Acta Paediatr. 2009 Oct;98(10):1667-73.

6. Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity. Free PDF.
Godfrey ME, Wojcik DP, Krone CA.
J Alzheimers Dis. 2003 Jun;5(3):189-95.

7. Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease. Free PDF
Valérie Leduc, Dorothée Domenger, Louis De Beaumont, Daphnée Lalonde, Stéphanie Bélanger-Jasmin, and Judes Poirier
Int J Alzheimers Dis. 2011; 2011: 974361.

8. Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history. (Email me for PDF)
Eisenberg DT, Kuzawa CW, Hayes MG.
Am J Phys Anthropol. 2010 Sep;143(1):100-11.


lightcan said...

Hi G,

what are the implications then?
Human diet in Africa was different from that from northern Europe with the seasonal overreliance on fatty meat. I think that I shouldn't eat high fat on a regular basis. So there is such a thing as metabolic typing, one might call it metabolic genotype? I heard a guy talking about personalised cancer therapies based on metabolism, not only disease type and stage, age, sex, etc. (on Dr. Mercola's site)

Dr. B G said...


The diet in Africa makes no difference because not many exited. The E4 exited and dominated the northern hemisphere. They apparently had genes for curiosity, creativity and impulsivity to leave Africa... (not unlike recent immigrants to the melting pot known as the USA).

The implications of nutrigenomics (DNA + diet/environmental interactions) are that certain genetic types are more vulnerable to environmental toxicants like heavy metals, dental amalgams, well water, living near lead/mercury industrial sites or coal burning plants, seafood consumption, etc.

I do believe in the value of metabolic typing -- it goes along the same lines of apoE typing.

However, if one is low thyroid, adrenally depleted and has pancreatic insufficiency from SIBO (leaky gut), then yes eating a high fat diet on a regular basis will be extremely problematic. Fixing the organs first will yield untold benefits.

'Lipases' are supplemental pancreatic enzymes which help digest food. Proteases and amylases are conducive as well until the body heals and starts producing its own again.

I'm in the school of thought that if one has done paleo, improved stress/lifestyles and a couple of supps (n-3, enzymes, minerals) and the neolethal damage has not repaired, then 2 things need to still be addressed:
(a) environmental toxicants (metals, solvents, PCBs, etc)
(b) opportunistic infections -- parasites and/or SIBO (clostridia, candidiasis, etc)

Good luck :)


Aaron Blaisdell said...

Very thought provoking as usual! It's so often overlooked that it bears repeating again and again: diet is not the only contributor to health. Lifestyle factors (REM), exposure to environmental toxins (e.g., Metallica and Mega Death), and even the frequency of changing ones clothes (Depeche Mode), all interact with our genes (and there's a lot of genetic variation across individuals) for phenotypic expression. The wrong toxins mixing with the wrong genes could lead to differences in growth (They Might Be Giants), dementia in old age (Erasure), and other health outcomes. Some even claim that developmental pathologies such as autism are linked to childhood vaccination (Sting), though that tale apparently has been put in a coffin (Nine Inch Nails). Hopefully we can use our understanding of the limited knowledge we have among the sea of many unknowns to navigate at least a moderately successful attempt at achieving health in the modern world (Nirvana). I was born a baby (Genesis), but hope to become a Prince (TAFKAP)! Owwa!

lightcan said...

Thanks, G.

I must be one of those then as I left Romania in 1991 (joke)
It's nice to talk about it in the hypothetical, but until somebody really does the tests, establishes adrenal imbalances or I do a chelation protocol to see if there is a difference, nothing is going to change. I do think I have a gut flora problem resistant to simple repopulation techniques. Gum disease in my late 20s with bone loss at 35, acne starting at 33 2 years after I moved to Ireland from Hungary should raise a few red flags for an integrative/functional doctor. On paleo/high-fat started in 2008 I lost 36 kg in 2 years and all basic bloods looked good (high HDL, low trigs) except T3 and LDL.
What you do is fringe medicine. No chance for us over here to get that kind of service.

P.S. I'm going to miss Fringe, the show.

Ed said...

Wow, very cool.

I wonder if consumer gene testing includes apoE subtype? Like 23 and me. Will look later.

Dr. B G said...



Mashup MASTER...!!

I never knew heavy metals and evolution could be so s*xxxy (Pour Some Sugar on Me). As earth is always evolving we forget how frail and tenuous life is... e.g. Northridge and Fukushima (Forever Young). Your summary of the factors that make up this dance of life and the complex interplays is sublime (Sweetest Perfection). Thanks for co-creating and organizing AHS (Nothing Compares 2U) which'll be totally rad (Black celebration, Just Can't Get Enough). You're exploring and building a new terrain (Like a Virgin) *hee*. For me, many of the paradigms in my little head have been shifted, shafted, and shattered recently (Blasphemous Rumors) and can't trust any major group (Ship of Fools) - EPA, Monsanto, AMA, ADA, ADA etc (Lie To Me) - except my primal/PP/ancestral compatriots (Policy of Truth). We're so ready for change (HAMMERTIME). Our community just cr*cks me the f*ck up ...when Archevore stops blogging, people's lives just about fall apart *haa* (Personal Jesus) or Matesz starts singing a new song (Say Hello Wave Goodbye). I love the community in a crazy way (Every Breath U Take) because we meld humanity and history with science. To paraphrase a rat, humans 'They don't just survive. They discover, they create.'

*haaa ahaa!* G

Dr. B G said...


I know what you mean and it's frustrating until the light is shone in more concrete ways. At one time the earth was 'flat'... I do have many hopes that the fringe will be not only embraced but taught and evolved in higher manners in the very near future.

When I read a book or meet an expert, I'm in awe b/c they are light years ahead of the mainstream. We're getting there.

You probably have metal issues like 95% of the world. The only 5% that don't, are those that have been chelated or have natural genetic gifts.

Here's a good protocol ck out:

I take the cardiac am/pm product -- it's effect, safe and gradual in efficacy.

YOu can do your own hair test but this will not provide info until the metals from the tissues/glands start to come out. If the liver isn't strong to perform the detox pathways and not enough fiber is consumed to excrete via bile/bowel then the toxins can be reabsorbed fyi.

Let me know how your path evolves. You've made Huuuuugge successes! Temporary support of thyroid and adrenals can yield enormous benefits for mind and body and toxin elimination...


I think BHL and liposcience and doctor's data and genova all offer it. Since E4 is common in Alz and heart disease it is commonly tested now for cheap.


TedHutchinson said...

I wonder to what extent the potential increased CVD/Diabetes/AD risk AP0E 4 carriers experience living nearer the equator may be prevented by extra melatonin that should be secreted by those living nearer the poles in winter?

Oxidative stress caused by mitochondrial calcium overload

melatonin may be a useful tool for the treatment of disease states and processes where an excessive production of oxidative damage occurs.

Neuroprotection by melatonin.

While I think most people grasp the idea that from dawn to dusk our skin, given the benefit of UVB exposure, is programmed to produce large amounts of vitamin D3, I think many forget that from dusk to dawn our Pineal glands are set to secrete Melatonin, given the benefit of darkness.

Like vitamin D3, melatonin is not only antiinflammatory, antioxidant but also antimicrobial.

Dr. B G said...


As always I appreciate all of your thoughts and contributions. I LOVE MELATONIN ;)

It is as important as vitamin D, your first love *ha*

In the theme I am heading, melatonin has an expansive role in regulating our integrational and organized health. Prn, I take 3-5 to 10 to 40 mg at night for several benefits. Unlike yoga megamasters, I cannot drink my OWN URINE.


mercury subacute injury bp, GSH, baroreceptor response melatonin protective

melatonin in alz -- helpful

J Pineal Res. 2011 Jan;50(1):8-20.
Matrix metalloproteinases in health and disease: regulation by melatonin.
Swarnakar S, Paul S, Singh LP, Reiter RJ.

Department of Physiology, Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
Matrix metalloproteinases (MMPs) are part of a superfamily of metal-requiring proteases that play important roles in tissue remodeling by breaking down proteins in the extracellular matrix that provides structural support for cells. The intricate balance in protease/anti-protease stoichiometry is a contributing factor in a number of diseases. Melatonin possesses multifunctional bioactivities including antioxidative, anti-inflammatory, endocrinologic and behavioral effects. As melatonin affects the redox status of tissues, the association of reactive oxygen species (ROS) with tissue injury under different circumstances may be mitigated by melatonin. Redox signaling is expanding into all areas of basic and clinical sciences, and this timely review focuses on the topic of regulation of MMP activities by melatonin. This is a rapidly growing field. Accumulating evidence indicates that oxidative stress plays an important role in regulating the activities of MMPs that are involved in various cellular processes such as cellular proliferation, angiogenesis, apoptosis, invasion and metastasis. This review offers sections on MMPs, melatonin, major physiological and pathophysiological conditions in the context to MMPs, followed by redox signaling mechanisms that are known to influence the cellular processes. Finally, we discuss the emerging molecular mechanisms relevant to regulatory actions of melatonin on the activities of MMPs. The possibility that melatonin might have therapeutic significance via regulation of MMPs may be a novel approach in the treatment of some diseases.

lightcan said...

Thanks, Dr. G
I'm not good at the moment, depressed and stressed, close to crying any moment, can't fall asleep sometimes although felt sleepy before getting ready to go to bed, sometimes because my extremities are cold; acne and gum disease worsened. Maybe T3 needs recalibrating, maybe I'm still not addressing the real causes.

Dr. B G said...

Lightcan Honeydear,

I am so sorry you are not feeling your most optimum and best... CHICKY, HANG IN THERE for there are so many solutions... so you're stressed and depressed and super tired but wired??

We just came back from camping (in a tent versus MISS-MY-HOTEL-ROOM) and it was interesting how my sister and I noticed how we were so sleepy and tired by 8pm-ish as the sun was going down. Granted there was also nothing to do b/c our lighting was quite compromised (we forgot the lamp) and were pooped from light hiking and waking up at the butt-crack of dawn (she has an active 3year old). Resetting the circadian rhythm of life is remarkably so easy in non-industrial settings!!

OK so your Free T3 is still low and not addressed yet? The root causes of much hypothyroidism is sometimes a mixture of the below, I have observed:
--low adrenal function (these sync together like your iphone/computer)
--leaky gut/SIBO
--candida overgrowth in the small intestines and possibly elsewhere
--diet, lifestyles, lack of oxygenating/aerobic exercise, stress
--yes you sound apoE4 with your LDL values and likely are harboring and hoarding endocrine disrupting environmental metals (doesn't take much sometimes depending on the person, like E4)

You probably need:
--a vacation *big wink and hug*
--non-antigenic diet (when do you feel the least bloated, acne, cold?)
sticking w/cooked vegs, raw salads and some chicken/lamb? little rice or potatoes?
--mild exercise like walking/jog in the morning to perk up that circadian pattern for better hormones (don't over push the adrenals) and open up the peripheral circulation. exercise alone can improve low thyroid (but strenous exercise can worsen by pooping out the adrenals)
--thyroid, adrenal and some progesterone support
--enzymes to digest + chew up the junk in circulation (because the digestion due to gut dysbiosis is wiped out to smithereens) [I like NOW superenzymes w/meals and Virastop2x from taken between meals]
--decent probiotic preferably with some soil organisms (flora balance, primal defense also at
--melatonin for sleep and minimize caffeine and alcohol (because it disrupts REM and can increase leakiness of the gut)

Keep in touch? Let me know what works for you and what doesn't.

Don't give up HOT MAMA :) !!!!

love, grace