Mutations The Foundation of Creation?

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MutationsThe Foundation of Creation?

• Sean Pitman, MD
• www.DetectingDesign.com
• 1/28/06

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Mutations copying errors

• ATT,GCC,GGT
• AAT,GCC,GGT
• THE CAT AND THE HAT
• THE RAT AND THE HAT
• MAQUIZILIDUCKS
• MAQUIZILIDUCCS

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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

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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

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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

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Sequence Space
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Random Walk

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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
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What About Devolution?

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

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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.

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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 arent we extinct after millions of years?

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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.

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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
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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.

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William R. Rice, Requisite mutational
load, pathway epistasis, and deterministic
mutation accumulation in sexual versus
asexual populations, Genetica 102/103 7181,
1998. 71
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Now What?

• Crows 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.   

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So, Whats 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?

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Hypothetical Example

• Population 5,000 (2,500 couples)
• Detrimental mutations per individual 7
• Detrimental mutation rate 3/individual/generatio
  n
• 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?

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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?

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• 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. 

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• 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. 

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• 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.

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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. 

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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 dont share a common
  ancestor which means that we are headed for
  extinction, but havent been around long enough
  to get there.
• The detrimental mutation rate is really low,
  humans and apes dont 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).

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