As usual, my policy is not to comment on posts from guests, especially those that disagree with my views. So here's Branko Kozulic's latest take on the "evidence" as he see it.
I thank Professor Moran for posting my text.Beerli, P. and Felsenstein, J. (2001) Maximum likelihood estimation of a migration matrix and effective population sizes in n subpopulations by using a coalescent approach. Proc. Natl, Acad. Sci. (USA) 98:4563–4568. [doi:10.1073/pnas.081068098]
This reply to the comments has grown in size much more than initially anticipated. At the outset, to prevent misunderstandings, I declare my complete ignorance of paleontology and, in general, that my ignorance is by far larger than my knowledge. And I am prepared to repeat this as many times as the readers are willing to read it.
From this discussion up to date, it seems that we do not have a simple model that could show the fixation of 22,000,000 mutations. And that no simple model will work becomes evident, for example, with just a glance at the Beerli & Felsenstein paper.
The referring of our colleague McBride to the Li & Durbin paper provides an opportunity to touch upon two other topics. In addition to the Li & Durbin article, I have carefully read also the paper by Gronau et al., dealing with the same topic. Both research groups started with the data derived from the sequenced genomes of several humans (7 and 6, respectively) from various sub-populations, with the goal of illuminating past fluctuations of the effective population size. Both groups arrived at similar results: thus the first paper reports for the Yoruba population the Ne of 15,313 ± 559, while the second paper gives the range of 7,500 to 10,500. Given this congruence of the results and the quality of the journals in which the results are published, I have no doubts about correctness of the results: I trust in internal consistency of these results. But they depend on certain starting assumptions, like all other results that are an outcome of scientific models. Now it´s time to look closer at the starting assumptions of these models because there is an external inconsistency – with another set of experimental data – as will become apparent in view of other three papers.
Figure 1 of Nielsen et al., paper shows multiple (up to 21) synonymous and non-synonymous substitutions in thousands of chimp proteins compared to the related human proteins. In the second paper Behe & Snoke conclude that in order to generate a new function that requires mutations of two amino acids, like forming a disulfide bridge, 108 generations are needed with a population size of at least 109. In the third paper, Lynch countered that much smaller populations could reach this goal in less time. Now, if we take the human population size from the above two studies (Ne about 104) for the population size in Figure 3 of the Lynch article, we can see that it would take 108 generations for the arrival of a new function, even if the two changed amino acid were any 2 of 50 (with a high s = 0.01). For humans, 108 generations mean 2 Billion years: an impossibly long period. Needless to say, a new function requiring 3, 4 … up to 21 amino acid changes would take much longer than 108 generations. And yet there about 3,000 proteins with 3 amino acid substitutions, over 1,000 proteins with 5 substitutions, etc. A contradiction is thus evident between the experimental data on the one side and the Lynch model plus Li & Durbin and Gronau et al., modeled results on the other, by a wide margin. Therefore, either the starting assumptions of the Lynch model, or of the human population size models, or of both, are false.
Furthermore, we should not lose sight of singletons/orphans found in all sequenced genomes. Population genetics – which deals with changes of allele frequencies in populations – necessarily will remain “agnostic” in relation to the singletons: they are, simply put, beyond its horizon.
Some of the comments referred to religious implications. I deny the existence of direct contact between scientific conclusions and religion. In my view, each particular scientific conclusions must pass through the filter of philosophy and exit at the other side as part of a general statement (universal); then universals are incorporated into a philosophical system, and that philosophical system may or may not be in accordance with philosophy (or theology) of a religion. The only level at which the implications of scientific conclusions can be meaningfully discussed is the philosophical level, in my opinion.
Allow me to conclude with additional philosophical thoughts. Science is no democracy, but a dictatorship. A dictatorship of experimental data: and only of experimental data. Can a scientist ignore the experimental data that contradict his favorite theory without betraying his vocation of scientist? I do not think so.
Moreover, I do not expect other scientists to provide answers to all my questions; nor can I answer all their questions: this is the normal state of affairs.
I wish to extend my thanks to all participants, especially Professor Felsenstein, for their courtesy shown during this discussion.
Behe, M.J. and Snoke, D.W. (2009) Simulating evolution by gene duplication of protein features that require multiple amino acid residues. Protein Science 13:2651–2664. [doi: 10.1110/ps.04802904]
Gronau, I., Hubisz, M.J., Gulko, B., Danko, C.G., and Siepel, A. (2011) Bayesian inference of ancient human demography from individual genome sequences. Nature Genetics 43:1031–1034. [doi: 10.1038/ng.937]
Li, H. and Durbin, R. (2011) Inference of human population history from individual whole-genome sequences. Nature 475:493–496. [doi: 10.1038/nature10231]
Lynch, M. (2009) Simple evolutionary pathways to complex proteins. Protein Science 14:2217–2225. [doi: 10.1110/ps.041171805]
Nielsen, R., Bustamante, C., Clark, A.G., Glanowski, S., Sackton, T.B., Hubisz, M.J., Fledel-Alon, A., Tanenbaum, D.M., Civello, D., White, T.J., Sninsky, J.J., Adams, M.D., and Cargill, M. (2005) A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees. PLoS Biology doi: 10.1371/journal.pbio.0030170