No, Mark, that's not something I know -- it's one of the things you made up. Any geneticist knows that there are plenty of changes in brain-related genes that don't have significant deleterious effects. That's because we know that there are lots of genetic variants in brain-related genes floating around in the population -- we've all got lots of them -- and yet most of us are pretty functional. Your problem is ascertainment bias: you're looking only at a tiny subset of mutations, those deleterious enough to send someone to the mental retardation clinic. Of course, those mutations are almost always going to be deleterious.
We are not talking about a minor adaptive trait that can be accounted for by gene expression or a serendipitous effect now and again. We are talking about a vital organ undergoing a major overhaul and brain related genes don't respond well to mutations. That's the negative side, on the positive side there has to be a molecular mechanism capable of developing a brain that is three times bigger and vastly more intelligent.
At what point is the null hypothesis for this assumed transition demonstrative proof that it's not possible?
We also don't have to know what the non-deleterious mutations are to know that they exist. We know that differences in IQ in normal individuals are partly genetic, so there have to be genetic differences that subtly effect brain performance without wrecking the brain. And that's all that's needed for selection to operate on. Please explain how intelligence could be in part inherited if all brain mutations are severely deleterious.
Your talking about behavior and the expressed traits within our now closed species. I'm talking about an ape sized brain doubling and nearly tripling to say nothing of the requisite traits making it possible.
I'm pretty sure I'm in a better position to evaluate the differing scientific requirements of physics and evolutionary biology.
Which tells me that there is nothing empirical telling us the molecular basis for the evolution of the human brain from that of apes. If there were, you would have at least mentioned it.
Huh? The great majority of coding mutations are missense (i.e they change an amino acid in the protein), not nonsense (i. e. they truncate the protein). (And most nonsense mutations aren't frameshift mutations; they're single-base substitutions that create a stop codon.) Any introduction to genetics should tell you this;
here is one paper among many with relevant information.
Been there done that and I'm not interested in chasing this in circles, stay on point. Three out of four protein coding genes in the human genome diverge by at least one codon per species as compared to Chimpanzees. Whatever the tedious specifics are deleterious effects are all you can reasonably expect from a mutation in a brain related gene:
We combined analysis of mutations causing human Mendelian diseases, of human-chimpanzee divergence, and of systematic data on human genetic variation and found that ~20% of new missense mutations in humans result in a loss of function, whereas ~27% are effectively neutral. Thus, the remaining 53% of new missense mutations have mildly deleterious effects.
Most Rare Missense Alleles Are Deleterious in Humans: Implications for Complex Disease and Association Studies
A prime example would be Cystic Fibrosis
Missense mutations
With a missense mutation, the new nucleotide alters the codon so as to produce an altered amino acid in the protein product.
EXAMPLE: sickle-cell disease. The replacement of A by T at the 17th nucleotide of the gene for the beta chain of hemoglobin changes the codon GAG (for glutamic acid) to GTG (which encodes valine). Thus the 6th amino acid in the chain becomes valine instead of glutamic acid...
...Here is a sampling of the more than 1000 different mutations that have been found in patients with cystic fibrosis. Each of these mutations occurs in a huge gene that encodes a protein (of 1480 amino acids) called the cystic fibrosis transmembrane conductance regulator (CFTR).
Mutations
Moreover, ~90% of mutations that affect protein-coding genes don't change the coding sequence at all. Instead, they change regulatory elements, changing how much, when or where the protein is produced.
That is a long way from a positive proof for the molecular basis for the human brain evolving from that of apes.
