Robert Marks’s Evolutionary Informatics Lab

Strongly endorse the recommendation to:
Dr. John C. Sanford, Genetic Entropy & The Mystery of the Genome. 2005 Ivan Press ISBN 1-59919-002-8.

Following are major technical papers he reviews in Appendix 1.

J.B.S. Haldane 1957 The Cost of natural selection. J. Genetics 55:511-524
“natural selection cannot occur with great intensity for a number of characters at once.” “the mean time taken for each gene substitution is about 300 generations.”

See followup by
Walter Remine 2005. Cost of Selection Theory. Technical Journal 19:113-125.

Kimura, M. 1968. Evolutionary rate at the molecular level. Nature 217:624-626.
“the substitutional load becomes so large that no mammalian species could tolerate it” … “the mutation rate per generation for neutral mutationhs amounts to roughly … four per zygote…”.

Kimura, M. The Neutral Theory of Molecular Evolution, 1983 Cambridge Univ. Press p 27
“to maintain the same population number aqnd still carry out mutant substitutions … each parent must leave … 3.72 million offspring to survive and reproduce.”

Muller, H.J. 1950. Our load of mutations. Amer. J. Human Genetics 2:111-176.
“the present number of children per couple cannot be great enough to allow selection to keep pace with mutation rate of 0.1.” pp 149-150.

Muller, H.J. 1964. The relation of recombination to mutational advance. Mutation Research 1:2-9.
“There comes a level of advantage, however, that is too small to be effectively seized upon by selection, its voice being lost in the noise, so to speak.”
“… an asexual population incorporates a kind of rachet mechanism, such that … lines become more heavily loaded with mutation.”

J. V. Neel et al. 1986. The rate with which spontaneous mutation alters the electrophoretic mobility of polypeptides. PNAS 83:389-393.
“… gamete rates for point mutations … on the order of 30 per generation… The question of how our species accommodates such mutation rates is central to evolutionary thought.”

A. S. Kondrashov. 1995. Contamination of the genome by very slightly deleterious mutations: Why have we not died 100 times over? J. Theor. Biol. 175:583-594.
“accumulation of VSDMs in a lineage … acts like a timebomb … the existence of vertebrate lineages … should be limited to 10^6 to 10^7 generations.”

S. Kondrashov. 2002. Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Human Mutation 21:12-27.
“… the total number of new mutations per diploid human genome per generation is about 100 … at least 10% of these are deleterious … analysis of human variability suggests that a normal person carries thousands of deleterious alleles…”.
(Kondrashov privately estimates up to 300 /generation with 30% deleterious.)
Sanford notes: “U”(deleterious mutations per person per generation) would be 30-90. This is 100-fold higher than would have previously been considered possible.

M. W. Nachman & S.L. Crowell 2000. Estimate of the mutation rate per nucleotide in humans. Genetics 156:297-304.
“The human diploid genome … about 175 new mutations per generation. The high deleterious mutation rate in humans presents a paradox. If mutations interact multiplicatively, the genetic load associated with such high U would be intolerable in species with a low rate of reproduction …”

A. Eyre-Walker and P Keightley. 1999. High genomic deleterious mutation rates in Huminids. Nature 397:344-347.
“average of 4.2 amino-acid-altering mutations per diploid per generation have occurred in the human lineage…”. “a large number of slightly deleterious mutations may therefore have become fixed in huminoid lineages … it is difficult to explain how human populations could have survived… a high rate of deleterious mutation n(U>>1) is paradoxical in a species with a low reproductive rate…”

J. F. Crow. 1997. The high spontaneous mutation rate: is it a health risk? PNAS 94:8380-8386.
“It seems clear that for the past few centuries harmful mutations have been accumulating…The decrease in viability from mutation accumulation is some 1-2% per generation… I regard mutation accumulation as a problem. It is something like the population bomb, but with a much longer fuse.”

M. Lynch, J. Conery & R. Burger, 1995. Mutation accumulation and the extinction of small populations. The American Naturalist 146:489-518.
“…synergistic interaction between random genetic drift and mutation accumulation, which we refer to as mutational meltdown … the length of the meltdown phase is generally quite short.” … “for genetic reasons alone, sexual populations with effective population sizes smaller than 100 individuals are unlikely to persist for more than a few hundred generations…”

K. Higgins & M. Lynch. 2001. Metapopulation extinction caused by mutation accumulation. PNAS 98:2928-2933.
“with mutation accumulation the extinction time is just slightly longer than 100 generations…” (vs 2000). “… the mild mutational effects are most damaging, causing minimal time to extinction.”

Fred Hoyle. 1999. Mathematics of Evolution. Acorn Enterprises, LLC Memphis.
“This long term inability of natural selection to preserve the integrity of genetic material sets a limit to its useful life…”.

Howell et al. 1996. Evolution of human mtDNA. How rapid does the human mitochondrial genome evolve? A. J. Hum. Genet. 59:501-509.
… how (or whether) organisms can tolerate, in the sense of evolution, a genetic system with such a high mutational burden.”
Sanford notes “just 0.1 -1.0 mitochondrial mutations per person create insurmountable problems for evolutionary theory.”

Sanford gives numerous other population based challenges evolution. On p 139 he summarizes:
“We have reviewed compelling evidence that even when ignoring deleterious mutations, mutation/selection cannot create a single gene – not within the human evolutionary timescale. When deleterious mutations are factored back in, we see that mutation/selection cannot create a single gene – ever. This is overwhelming evidence against the Primary Axiom. In my opinion this constitutes what is essentially a formal proof that the Primary Axiom is false.”

Avida developers stated:”…our experiments showed that the complex feature never evolved when simpler functions were not rewarded.”
Lenski, Ofria, Pennock & Adami, “The evolutionary origin of complex features.” Nature vol 423, 139-144 (8 May 2003)

While evolution “must” have beneficial mutations, almost all recorded mutations are harmful.

Bergman found 453,732 “mutation” hits in Biological Abstracts and Medline. Of these 186 mentioned “beneficial” of which all involved loss-of-function.
Bergman, J. 2004. Research on teh deterioration of the genome and Darwinism: why mutations result in degeneration of the genome. Intelligent Design Conference, Biola Univ. April 22-23.

Mutations are registered in:
Online Inheritance In Man OMIM
http://www.greencarcongress.com/2006/01/index.html
OMIM Statistics for June 4, 2007
17,717 entries.

Gerrish and Lenski estimate the rate of harmful to beneficial mutations at 1 million:1
Gerrish, P.J. & R. Lenski, 1998. Theh fate of competing beneficial mutations in an asexual population. Genetica 102/103: 127-144.

Thus while Avida requires a sequence of beneficial mutations, actual mutations are almost all harmful.

Furthermore, numerous mutations occur simultaneously. Mot of these cannot be selected out and build up, eventually causing species death.

Sanford details numerous other factors, each of which can result in species death.

Recommend working towards building these factors into your models to demonstrate the reality of genomic entropy via evolutionary degradation, and the associated mathematical foundations that must be incorporated into realistic evolutionary search models.