MutationsThe Foundation of Creation?

Sean Pitman, MDwww.DetectingDesign.com

1/28/06

Mutations = copying errors

• ATT,GCC,GGT• AAT,GCC,GGT

• THE CAT AND THE HAT• THE RAT AND THE HAT

• MAQUIZILIDUCKS• MAQUIZILIDUCCS

Mutations Can Be:

• Beneficial – antibiotic resistance

• Neutral – no change in function

• Detrimental – loss of beneficial function

• Note: The vast majority of mutations that affect function are detrimental

The Mechanism of Evolution

• Random Mutation and Natural Selection

• Nature sees both the good and the bad mutations and preferentially selects to keep the good and get rid of the bad

• Therefore, evolution is not random as many creationists argue since Nature selects in an nonrandom way

Mostly Bad Options• Sequence Space = all potential options

– How many possible 3-letter sequences?– 263 = 17,576

• Different levels of sequence space– How many possible 7-letter sequences?– 267 = 8,031,810,176

• Lower Levels = higher ratio of good vs. bad – 972 defined 3-letter words– Ratio = 1 in 18

• Higher Levels = Exponentially less good vs. bad – 23,109 defined 7-letter words– Ratio = 1 in 347,561

Sequence Space

Random Walk

Comparison to Real Life?

• A gap of 32 Amino Acids: 4.29 x 10e41 (~100 thousand trillion trillion trillion)

• Total bacteria on Earth: 5 x 10e30 (5 million trillion trillion)*

• A checkerboard with 10e41 meaningless AA squares divided among 5 million trillion trillion bacteria would require each individual bacterium and its offspring (just one in a steady state population) to undergo a random walk of around 85 billion steps before success would be realized

• Time per step: ~10 years• Based on a very high mutation rate of 10e-5 per sequence

per generation (one mutation every 100,000 generations) with a generation time of 1 hour

• Average time to success: ~850 billion years

*http://news.bbc.co.uk/1/hi/sci/tech/158203.stm

What About Devolution?

Can nature really get rid of all the bad mutations as fast and the come?

Mutation Rates• Human-chimp DNA comparisons used to

estimate mutation rates of ~2.5 x 10-8 per nucleotide site or 175 mutations per diploid genome per generation

• 175 mutations/generation seems reasonable• Each diploid fertilized zygote contains around 6

billion base pairs of DNA (~3 billion from each parent). The error rate for DNA polymerase combined with repair enzymes is about 1 mistake in 1 billion bp or 6 mistakes with each diploid replication. With a male/female average of about 29 mitotic divisions per gamete before fertilization, the average mutation rate is ~175.

Rate of Bad Mutations

• The latest detrimental mutation rate, based on differences between humans and chimps, is greater than 3 per person per generation – more recent estimates suggest a rate greater than 5.

• With a suggested detrimental vs. beneficial ratio of at least 1000 to 1, it seems like the buildup of detrimental mutations might lead toward extinction

• So, why aren’t we extinct after millions of years?

Nachmann and Crowell

• The high deleterious mutation rate in humans presents a paradox.  If mutations interact multiplicatively, the genetic load associated with such a high U [detrimental mutation rate] would be intolerable in species with a low rate of reproduction [like humans and apes etc.] . . . The reduction in fitness (i.e., the genetic load) due to deleterious mutations with multiplicative effects is given by 1 - e -U (Kimura and Moruyama 1966).  For U = 3, the average fitness is reduced to 0.05, or put differently, each female would need to produce 40 offspring for 2 to survive and maintain the population at constant size.  This assumes that all mortality is due to selection and so the actual number of offspring required to maintain a constant population size is probably higher.

Solving the Problem?

• The problem can be mitigated somewhat by soft selection or by selection early in development (e.g., in utero).  However, many mutations are unconditionally deleterious and it is improbable that the reproductive potential on average for human females can approach 40 zygotes.  This problem can be overcome if most deleterious mutations exhibit synergistic epistasis; this is, if each additional mutation leads to a larger decrease in relative fitness.  In the extreme, this gives rise to truncation selection in which all individuals carrying more than a threshold number of mutations are eliminated from the population.  While extreme truncation selection seems unrealistic [the death of all those with a detrimental mutational balance], the results presented here indicate that some form of positive epistasis among deleterious mutations is likely.

Nuchman, Michael W., Crowell, Susan L., Estimate of the Mutation Rate per Nucleotide in Humans, Genetics, September 2000, 156: 297-304

Synergistic Epistasis?• Synergistic or “positive” epistasis basically means a

multiplicative instead of an additive effect of detrimental mutations

• What if all those with at least 3 detrimental mutations died before reproducing?

• The average detrimental load of a population would soon hover just above 3 detrimental mutations

• Over 95% of the subsequent generation would now have 3 or more bad mutations

• The reproductive rate of the remaining 5% would have to increase dramatically to keep up with the death rate – problem not solved.

William R. Rice, Requisite mutational load, pathway epistasis, and deterministic mutation accumulation in sexual versus asexual populations, Genetica 102/103: 71–81, 1998. 71

 

Now What?

• Crow’s answer is that sex, which shuffles genes around (genetic recombination), allows detrimental mutations to be eliminated in bunches.  The new findings thus support the idea that sex evolved because individuals who (thanks to sex) inherited several bad mutations rid the gene pool of all of them at once, by failing to survive or reproduce.   

So, What’s So Good about Sex?

• Genetic recombination allows the potential for concentration of both good and bad mutations

• For example, lets say we have two individuals, each with 2 detrimental mutations. Given sexual recombination between these two individuals, there is a decent chance that some of their offspring (1 chance in 32) will not have any inherited detrimental mutations.   But, what happens when the rate of additional detrimental mutations is quite high - higher than 3?

Hypothetical Example

• Population = 5,000 (2,500 couples)

• Detrimental mutations per individual = 7

• Detrimental mutation rate = 3/individual/generation

• Reproductive rate = 4 per couple = 10,000 offspring

• In one generation, how many offspring will have the same or fewer detrimental mutations compared with the parent generation?

Inherited After Ud = 3

7  901

6 631

5 378

4 189

3 76

2 23

1 5

0 0.45

< or = 7  2202

Poisson Approximation

• This Poisson approximation shows that out of 10,000 offspring, only 2,202 of them would have the same or less than the original number of detrimental mutations of the parent population.  This leaves 7,798 with more detrimental mutations than the parent population

• Now what?

• In order to maintain a steady state population of 5,000, natural selection must cull out 5,000 of these 10,000 offspring before they are able to reproduce

• Given a preference, those with more detrimental mutations will be less fit by a certain degree and will be removed from the population before those that are more fit (less detrimental mutations). 

• Given strong selection pressure, the second generation might be made up of ~2,200 more fit individuals and only ~2,800 less fit individuals with the overall average showing a decline as compared with the original parent generation. 

• If selection pressure is strong, so that the majority of those with more than 7 detrimental mutations are removed from the population, the next generation will only have about 1,100 mating couples as compared to 2,500 in the original generation. 

• With a reproductive rate of 4 per couple, only 4,400 offspring will be produced as compared to 10,000 originally.  In order to keep up with this loss, the reproductive rate must be increased or the population will head toward extinction. 

• In fact, given a detrimental mutation rate of 3 in a sexually reproducing population, the average number of offspring needed to keep up would be around 20 per breeding couple (2eUd/2).  While this is about half that required for an asexual population (2eUd), 20 offspring per couple is still quite significant.

• If the detrimental mutation rate were at greater than 5, as many current estimates suggest, the average reproductive rate would have to increase to more than 150 offspring per average couple.

Men Are the Weaker Sex

• Men contribute the most to the detrimental mutation rate AND the chromosome that makes us different from women, the all-important Y-chromosome, does not undergo significant sexual recombination.

• Are the males of slowly reproducing species, like humans, therefore headed for extinction at an even faster rate than females? 

• It doesn't seem quite clear as to just how the Y-chromosome could have evolved over millions of years of time given its relative inability to combat high detrimental mutation rates. 

So, Why Are We Still Here?• My understanding of population genetic could be

way off? – which is quite likely . . .• The detrimental mutation rate is very high and

humans and apes really don’t share a common ancestor – which means that we are headed for extinction, but haven’t been around long enough to get there.

• The detrimental mutation rate is really low, humans and apes don’t share a common ancestor, and we are not headed for extinction.

• Humans and apes do share a common ancestor, but this ancestor only lived a few thousand years ago (not 8 million).