My Momma Is A Mutant (Genetics and Mutations –the Driving Change in Life)

 

The Science

The intersection of genetics and evolutionary theory is currently one of the most active areas of scientific debate.  Whether mutations are "consistent" with evolution depends entirely on which mathematical model or biological scale you are looking at.  To provide a balanced view, we have to look at the evidence that supports the standard model and the specific genetic challenges that have been raised recently.

The standard scientific view (Neo-Darwinism) holds that while most mutations are neutral or harmful, the rare "beneficial" ones are powerful enough to drive progress over millions of years.  Even if 99.9% of mutations are bad, natural selection acts as a "filter" and ruthlessly eliminates the bad ones and preserves the 0.1% that provide a survival advantage.

Genetics has shown that sometimes an entire gene is accidentally copied. One copy keeps doing its original job, while the "extra" copy is free to mutate and eventually develop a completely new function.  We have identified genes ("De Novo") in various species that appear to have evolved from non-coding DNA ("junk DNA") into functional instructions, showing that new information can indeed arise.

In recent years, several high-profile geneticists and mathematicians have pointed to data that they believe contradicts the standard "upward" evolutionary model.  As mentioned in the work of Dr. John Sanford 1, many mutations are only slightly harmful—not enough to kill the organism, but enough to slightly degrade its "software."  Because these mutations are "nearly neutral," natural selection cannot "see" them to pull them out of the population. Over time, these un-selectable "typos" build up.  Critics argue this leads to Genetic Entropy (biological decay) rather than evolution.

To "verify" the nearly neutral problem, Sanford and his colleagues developed a software program called “Mendel’s Accountant", which simulates mutation accumulation over generations.  These papers argue that even with "strong" natural selection, the "nearly neutral" mutations (those with a fitness effect of less than 10-4 or 10-5) are essentially invisible to selection and will accumulate regardless of the organism's survival.

Another issue called the "Waiting Time" problem is a mathematical challenge regarding how long it takes for a specific set of mutations to appear.  If a new trait requires two or more specific mutations to work (where the first mutation by itself is useless), the math becomes difficult.  Some researchers calculate that for a population of primates to "wait" for just two specific coordinated mutations could take hundreds of millions of years—far longer than the 6–7 million years since the supposed human-chimp split.

The "Haldane’s Dilemma" is a classic problem in population genetics regarding the "cost" of natural selection.  To "fix" a new beneficial mutation in a whole population, many individuals who don't have that mutation must die off or fail to reproduce.  Critics argue there hasn't been enough "death" (selective pressure) in human history to account for the millions of genetic differences between humans and our closest supposed ancestors.

The genetic timeline and entropy are serious questions about evolution.  Many mainstream geneticists acknowledge these "load" and "waiting time" problems but believe other mechanisms solve them, such as changes in how genes are expressed without changing the DNA sequence (Epigenetics) and the idea that the genome is "pre-programmed" to be flexible (Facilitated Variation), allowing for quick changes that look like evolution but are actually built-in adaptability.  However, others point out that this is just “wishful” science and has no grounded data.

Some scientists incorrectly base human genetic studies on observations of lower organisms.  To understand why mutations present a different challenge for humans than for bacteria, we have to look at the Mutation Rate per Generation.  While the "per-letter" (per base pair) error rate is often similar across life, the larger the genome and the longer the generation time, the more "typos" accumulate in each offspring.  In bacteria, a mutation is a rare event for an individual.  In humans, every single baby is born with a significant number of brand-new genetic "typos" that neither parent possessed.

Because only 1 in 1,000 bacteria has a new mutation, and there are trillions of bacteria, natural selection can easily "pick the winner" and discard the rest.  Because every human has 60 to 100 new mutations, natural selection has a much harder time.  If a baby has 70 slightly bad mutations and 1 good one, how does nature select the good one without also keeping the 70 bad ones?  This is the core argument of the "Selection Cost" or "Haldane's Dilemma."

When scientists study human mutations, they divide the search into two very different "libraries" of information: the Nuclear Genome and the Mitochondrial Genome.  The Nuclear Genome (The Main Library) is the DNA found in the nucleus of every cell, inherited from both parents.  This is approximately 20,000 to 25,000 protein-coding genes, or about 3.2 billion base pairs (letters).  This is where most "Waiting Time" problems are calculated because these genes control complex traits like brain size, upright walking, and skin physiology.  The Mitochondrial Genome (The Power Plant) is a tiny, circular loop of DNA found inside the mitochondria (the cell's energy producers).  It is inherited only from the mother.  It contains exactly 37 genes, or 16,569 base pairs.  Because it is so small and doesn't "recombine" (mix) like nuclear DNA, it is used as a Molecular Clock.  By counting the mutations in mitochondrial DNA (mtDNA), scientists trace lineage back to a single female ancestor, often called "Mitochondrial Eve."

The age of “Mitochondrial Eve" depends entirely on the Mutation Rate used in the calculation.  Originally, scientists estimated the rate by comparing human DNA to chimp DNA and assuming they split 6 million years ago (Phylogenetic Rate).  This gave a slow rate, placing "Eve" at 150,000 to 200,000 years ago.

More recently, scientists began measuring mutations in living families, comparing grandmothers to granddaughters, (Pedigree Rate). They found the actual mutation rate is much faster than previously thought.  If you use the faster, observed "Pedigree Rate," the calculation for "Mitochondrial Eve" can drop significantly—some studies suggest as recently as 6,000 to 10,000 years ago. 2

The age of “Y-Chromosomal Adam” is traced through the male Y-chromosome.  The Y-chromosome is located inside the nucleus and is part of the 23 pairs of chromosomes that make up the human genome.  Humans have 46 chromosomes in total (23 pairs). The first 22 pairs are called "autosomes."  The 23rd pair determines biological sex.  In biological males, this 23rd pair consists of one X-chromosome and one Y-chromosome (XY).

Because the Y-chromosome is passed exclusively from father to son, it acts as a digital "surname" that doesn't get mixed with the mother's DNA.  By tracing the mutations in this chromosome back through time, geneticists can mathematically "converge" every living man's lineage to a single individual.  

Because the Y-chromosome is tucked away in the nucleus but does not have a matching pair like the other 22 chromosomes, it undergoes a unique process.  For most of its length, the Y-chromosome does not "swap" or "mix" pieces with the X-chromosome.  This means that except for random mutations (the "typos"), a son’s Y-chromosome is a direct carbon copy of his father’s.  This is why it stays so consistent for thousands of years, allowing scientists to trace the "un-mutated" gene back to a single common ancestor.  The estimates for Adam's age vary from 120,000–156,000 years ago to 237,000–581,000 years ago depending on the sample being sequenced and the mutation rate used.

A good question to ask is, “what does the unmutated DNA look like so we know how far back is the original”?  If we knew the mutation rate (which is currently a hot debate), how far back do you take the mutations before you reach Adam and Eve, or the original un-mutated cells?  The "Golden Question" of molecular clocks is to know how many mutations have occurred.  You first need a “Reference Sequence" (the "Original") to compare against.  Since we don’t have a DNA sample from the original Adam or Eve, geneticists use three primary methods to reconstruct what that un-mutated gene likely looked like.

The most common way to guess at the original state of a gene is called the "Consensus" Method, which is to compare thousands of modern humans from different parts of the world (Africa, Asia, Europe, the Americas).  If 99% of all men on Earth have a "T" at a specific location on the Y-chromosome, but a small group in a specific village has a "G," scientists assume the "T" is the original state and the "G" is a mutation that happened later in that specific lineage.  By aligning thousands of sequences, they build a Consensus Sequence—a "Best Guess" of the ancestral DNA.

Another way is to use an "Outgroup" comparison (The Chimpanzee Reference) to determine which version of a gene is older. An outgroup is an assumed species that is related to humans but "branched off" earlier.  If humans have two versions of a gene (version A and version B), and chimpanzees only have version A, scientists conclude that Version A is the "Un-mutated" (Ancestral) state, and version B is a mutation that occurred in the human line after the split.  This method assumes that the "Common Ancestor" shared the same DNA as the outgroup.  If you do not believe in a common ancestor with apes, this method is considered invalid, as it "forces" the data to fit an evolutionary timeline.

Sometimes, scientists find a "Genetic Time Capsule" (Deep Rooting).  In 2013, a man in South Carolina was found to have a Y-chromosome (Haplogroup A00) that didn't match any other known human line.  This lineage was so different that it shifted the "Root" of the tree. By comparing this extremely rare, "ancient" line to the rest of humanity, scientists can see which mutations are shared by everyone else but missing in the A00 line. This helps "triangulate" back to an even older version of the "un-mutated" gene.

Once they have a "Best Guess" for the original sequence, they use the following simple formula to determine the date. 

T = D / 2 μ

T = Time (How many years ago they lived),

D = Genetic Divergence (The number of differences between two people),

μ  = Mutation Rate (How many "typos" happen per year).

The biggest variable in this equation isn't the DNA itself, but the Mutation Rate (μ).  We can guess as to the un-mutated gene by looking for the common denominator in all living humans. However, the date we assigned to that "Original Person" changes drastically depending on whether we use a "Slow Clock" based on apes or a "Fast Clock" based on modern human families.

The Summary

Modern genetics seems to counter the theory of evolution.  Human “typos” in gene transmission favor genetic entropy over long time periods and not a progression of complex organisms.  Also, real mutation rates based on actual human mutations does not support the “old age” fossil theory but a recent emergence of Adam and Eve.  It claims that Adam and Eve are just 6,000 - 10,000 years old!  This upsets the whole theory, so instead, let’s use chimp data to fudge the outcome.  Sorry Glen, but this looks like monkey business to me.

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1. Sanford, J. C. (2005). Genetic Entropy & the Mystery of the Genome. Ivan Press. (See specifically Chapter 3: The Problem of Mutation Selection and Chapter 4: The Problem of Selection Noise).

2. Parsons, T. J., et al. (1997). "A high observed substitution rate in the human mitochondrial DNA control region." Nature Genetics. This study noted that the observed rate was roughly 20 times higher than the rate predicted by evolutionary models.