Is there a measure of human genetic variation, where human genetic variation can differ more than 1%?

Question

According to this

Neardenthal genetics

The proportion of Neanderthal-inherited genetic material is about 1 to 4 percent[12] [later refined to 1.5 to 2.1 percent[11]] and is found in all non-African populations

And according to this

Interbreeding between archaic and modern humans

Neanderthal-derived ancestry is absent from most modern populations in sub-Saharan Africa

Now, human genetic variation is usually said to be between 0,1% to 0,5%

Genetics

While the genetic difference between individual humans today is minuscule – about 0.1%, on average

Why are the genomes of humans 99,5% the same

Human's DNA sequence is said to be roughly 99.5% equal

But here,

Human genetic variation

There are at least 6 different ways to measure human genetic variation and

human-to-human genetic variation is estimated to be at least 0.5%

Does this last affirmation and the first two articles tell us that the difference in human genetic variation, according to some measures of variation, it's actually more than 1% ? (larger than some ways to measure our genetical differences with other animals like chimps for example that are usually mentioned to highlight our similatiries) Or are there things missinterpreted in all this?

Answer 1

The question makes it clear that the poster is aware of the different ways of estimating human genetic variation, and he is also no doubt aware of the fact that Wikipedia is written by “people like you” who may not be experts in the field or have updated an old entry based on limited data. Let me address what appears to be the cause of confusion in this question — certainly in other questions on this topic.

For simplicity let us take a suitable round number for the Human/Neanderthal relatedness. Then the poster’s first quotation can be simplified as:

1. The proportion of Neanderthal-inherited genetic material in modern Europeans is 2%.

and his second quotation simplified as:

2. Neanderthal-inherited genetic material is absent from modern Africans.

A common conclusion drawn from this is:

The genetic variation between modern Europeans and Africans must therefore exceed 2%, rather than being only ca. 0.5%.

Why is this wrong?

This conclusion is wrong because the 2% and 0.5% are measures of different things.

For simplicity, a value of human genetic variation of 0.5% can be regarded as the extent by which the DNA of the coding regions of the genes of two humans differ because of single nucleotide polymorphisms (SNPs) — single base changes in the same gene (that may or may not affect the gene function). This assumes all humans have the same 20,000 or so genes.

Now let us make an overall comparison of the genes of humans and Neanderthals. Since they diverged from a common ancestor their genomes underwent changes due to point mutations, but, as far as I am aware, they maintained the same set of genes. Even if I am wrong on this latter point, the vast majority of genes — and the ones that we are concerned with are common: they both have/had a gene for myosin, for hexokinase 1, for chymotrypsin etc.

Examination of the majority of such homologous genes reveals single base differences, which must have arisen since the divergence. A combination of such Neanderthal variants in one gene — never seen as human SNPs — and the converse situation allow one to designate a chymotrypsin gene, for example, as human or Neanderthal, even though the overall DNA sequence of the chymotrypsin gene may be 95% identical (to conjure a figure out of the air).

Now consider the European/Neanderthal comparison. It turns out that a small number of genes show no (or almost no) variation between the two, but that most of these show the standard ca. 95% difference between Africans and Neanderthals (and hence between Africans and Europeans). These, then, are the 2% of genes that arose from interbreeding of Europeans and Neanderthals, after the exodus from Africa.

But 2% of genes of different origin which still retain 95% sequence identity would only add 0.1% to the modern human variation, cited at ca. 0.5%.

Disclaimer

I do not know the actual extent of variation between most human and Neanderthal genes or the details of the non-African genes of Neanderthal origin. I will be happy to edit this answer if anyone has that detail. I apologize for the geographical generalizations not present in the question, but my concern was to convey the argument without burdening it with continued qualifications.