Transcript Mutations The Foundation of Creation?

Mutations
The Foundation of Creation?
Sean Pitman, MD
www.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
Ychromosome, 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 Ychromosome 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).