I understand perfectly well what fixation means. I don't see how it's relevant, however, since we we're not talking about which genetic differences become fixed. We're just talking about the gross differences between genomes.
ThatÃ‚Â´s an essential point if you claim that the majority of mutations are neutral."Because of genetic drift, the ultimate fate of every neutral variation within a gene pool is either extinction or fixation.""When a new neutral mutation arises (let us say one A allele in a gene pool otherwise consisting of B alleles) then the process of genetic drift begins. And it begins with the A allele very close to extinction"
"This leads to a further rather neat result. Let μ be the rate at which neutral mutations occur, given as probability of mutation per nucleotide per generation. Then there will be μfNe mutations per site per generation in the population. Of these, only a fraction will go on to fixation, this fraction being given, as we have shown, by 1/fNe
. It follows that the rate of substitution (i.e. the fixation of new alleles, replacing the old ones) is given by μfNe/fNe --- which is just equal to μ.
In other words, the rate of substitution per site per generation in the entire gene pool is equal to the rate of mutation per nucleotide per generation in the individual"http://skepticwiki.o...p/Genetic_Drift
So, if we have 35 millions of neutral mutations fixed in our lineage then itÃ‚Â´s necessary to have occured 35 * 10^6 * 10^10 = 35 * 10^16 mutations.As we have 130 mutations per individual then itÃ‚Â´s necessary 2,69 * 10^15 individuals in 250,000 generations.It will lead us to 10.76 billions of individuals per generation for the last 5 million years.
For example, using the mutation rate from the blog you linked earlier, it pegs the rate of mutations at ~130 substitutions (single nucleotide) per person per generation. Assuming 5 million years of evolution with a mean generation time of 20 years, that means we have 250 000 generations. Assuming strictly neutral evolution, therefore the net accumulated difference from the ancestor to a current individual is going to be just 130x250000 = 32.5 million base pairs.
Your mistake is clear.You are ignoring genetic drift.
And if I want to double check this with data from another paper on mutation rates in mammalian genomes I can:
In this paper, they compute the average neutral mutation rate to be 2.22x10^-9 substitutions per site per year.
Note that this is based on a different unit measure (annual as opposed to generational). Based on the size of the genome (3 billion base pairs) times the rate (2.22x10^-9) times the distance (5 million years), yields a net accumulated difference from the ancestral population of 33.3 million base pairs. How about that?
First, You are again ignoring genetic drift, so your number is wrong.
Second, we can see reading the paper that the results are biased.The genes comparisions that gave the wrong results were discarded.So, itÃ‚Â´s not a surprise that the result is near the expected number, although 800 thousand of mutations is a large number.
"Homogeneity of Substitution Patterns Between Lineages.Although the fourfold-degenerate sites are expected to accumulate only synonymous substitutions, the evolutionary distances estimated by using these sites are useful in estimating the underlying mutation rate only if the nucleotide substitutions have accrued with the same substitution pattern in the two species compared. That is, the homologous sites in the two sequences compared in a given gene must have evolved with the same instantaneous substitution matrices. Substitution patterns in a given gene may shift in one lineage as compared with its orthologous counterpart for a number of reasons including chromosomal rearrangements (23), gene transfer (24), or centromere movement (e.g., mouse genome). In these cases, substitution patterns in genes may be affected to fix mutations that make the base composition of the gene to be more similar to its chromosomal location [amelioration effect (24)], and this will be more pronounced at the sites that are selectively neutral. Therefore, the substitution rate at neutral sites in those genes will be higher than the actual mutation rate (25), rendering such genes unsuitable for inferring mutation rates
. Therefore, we conducted the disparity index test for each pair of orthologous sequences (26, 27) to identify genes in which fourfold-degenerate sites are not evolving with homogeneous substitution patterns among the lineages compared
. The disparity index test directly examines the null hypothesis of homogeneity of the evolutionary pattern between two lineages by testing whether the observed difference in nucleotide frequencies between sequences is more than that expected by chance alone, given the number of differences observed between sequences. ( It seems to me circular reasoning, dont you think ? How do they know if the difference in nucleotide frequencies is more than expected by chance alone if the chance of mutation is what they want to discover ?).
It does not require the knowledge of the actual pattern of substitution, evolutionary relationships among species, or equality of substitution rates among lineages (26, 27). The disparity index test revealed that the fourfold-degenerate sites in a large number of genes have not evolved homogeneously in inter- as well as intraordinal comparisons (Fig. 2 a). For instance, sequences of the same gene in human and mouse are evolving with significantly different evolutionary substitution patterns in 1,703 of 3,722 comparisons (46%). The red closed circles in Fig. 2 b correspond to genes that were rejected by the disparity index test when the expected and observed difference in GC content was tested
. These genes clearly show much higher observed GC content difference than that expected by chance alone (the expected distribution is depicted by green open circles). On the contrary, GC content differences between human and mouse for the genes passing the disparity index test (black closed triangles) show a distribution that overlaps with the expected distribution
. It is apparent that mutations in the fourfold-degenerate sites are fixed with different patterns of substitution in different genes depending on the chromosomal context (e.g., isochore structure) in the genome (28). However, the observed differences in G + C content in fourfold-degenerate sites among genes may be an indication of differences in actual patterns of substitution or mutation among genes. Therefore, synonymous substitutions in a large number of genes are not suitable to use for inferring mutation rates
. In fact, the inclusion of genes (sequence pairs) evolving under heterogeneous evolutionary patterns would produce distance estimates that are higher than that expected for the genes evolving with homogenous substitution patterns.
Because different lineage comparisons show this heterogeneity to different extents (Fig. 2 c), estimates will be biased to different extents, which is likely to lead to erroneous conclusions regarding large mutation-rate differences among species (25). Both these problems are clearly evident in Fig. 2 c, which shows that the difference in evolutionary distances at fourfold-degenerate sites among the genes, which passed or failed the disparity index test, is as large as 46% (cow-pig comparison) and differs multifold among different species pairs. For this reason, all genes showing pattern heterogeneity in fourfold-degenerate sites should be and were removed from any further analyses
. This removal reduces the number of genes considerably (Fig. 2 a), but still the numbers of the fourfold-degenerate sites analyzed were quite large (682Ã¢â‚¬â€œ543,962; see Fig. 5 legend)."
Furthermore, we don't care which differences are accumulated. Indeed, if the population averages at 100,000 individuals, that means there are a total of 3.25 trillion possible mutations that could have occurred. But the majority of them get weeded out through random genetic drift.
ThatÃ‚Â´s the point 3.25 trillion possible mutations are not enough to fix 35 millions of mutations.