In the comments below a few days ago someone expressed concern at the diminishing of genetic diversity due to the disappearance of indigenous populations. My response was bascally that it depends. The issue here is whether that disappearance is due to assimilation, or extinction. If a given population is genetically absorbed into another, obviously their genetic diversity is by and large maintained. What disappears are the specific genotypes, the combinations of gene pairs, which are distinctive to that given group. This is the same dynamic at the heart of the ‘disappearing blonde gene’ meme. Unless there is selection at the loci which encode or predispose one to blonde hair the ‘gene’ isn’t going anywhere. Rather, the implicit issue here is that blonde people are intermarrying with non-blonde people, and if the genetic variant has a recessive expression then the frequency of the trait will decrease. Populations with a high degree of homozygosity at the ‘blonde loci’ are distinctive in a very particular manner, but they’re no more or less ‘diverse’ than other populations which don’t manifest the same tendency.
A toy example will suffice. Take two populations, A and B, and one locus, 1, with two variants, X and x. Assume that the two populations are the same size. At locus 1 population A is 100% X, and population B is 100% x. In a diploid scenario then all the individuals in population A will be XX, and in B will be xx. When you add A + B you get a frequency of X of 0.5, and of x of 0.5 (since the two populations are balanced in size).
The Pith: When it comes to the final outcome of a largely biologically specified trait like human height it looks as if it isn’t just the genes your parents give you that matters. Rather, the relationship of their genes also counts. The more dissimilar they are genetically, the taller you are likely to be (all things equal).
Dienekes points me to an interesting new paper in the American Journal of Physical Anthropology, Isolation by distance between spouses and its effect on children’s growth in height. The results are rather straightforward: the greater the distance between the origin of one’s parents, the taller one is likely to be, especially in the case of males. These findings were robust even after controlling for confounds such as socioeconomic status. Their explanation? Heterosis, whether through heterozygote advantage or the masking of recessive deleterious alleles.
The paper is short and sweet, but first one has to keep in mind the long history of this sort of research in the murky domain of human quantitative genetics. This is not a straight-forward molecular genetic paper where there’s a laser-like focus on one locus, and the mechanistic issues are clear and distinct. We are talking about a quantitative continuous trait, height, and how it varies within the population. We are also using geographical distance as a proxy for genetic distance. Finally, when it comes to the parameters affecting these quantitative traits there are a host of confounds, some of which are addressed in this paper. In other words, there’s no simple solution to the fact that nature can be quite the tangle, more so in some cases than others.
Because of the necessity for subtlety in this sort of statistical genetic work one must always be careful about taking results at face value. From what I can gather the history of topics such as heterosis in human genetics is always fraught with normative import. The founder of Cold Spring Harbor Laboratory, Charles Davenport, studied the outcomes of individuals who were a product of varied matings in relation to genetic distance in the early 1920s. This was summed up in his book Race Crossing in Jamaica:
A quantitative study of 3 groups of agricultural Jamaican adults: Blacks, Whites, and hybrids between them; also of several hundred children at all developmental stages. The studies are morphological, physiological, psychological, developmental and eugenical. The variability of each race and sex in respect to each bodily dimension and many basis vary just as morphological traits do. In some sensory tests the Blacks are superior to Whites; in some intellectual tests the reverse is found. A portion of the hybrids are mentally inferior to the Blacks. The negro child has, apparently, from birth on, different physical proportions than the white child.
The number 1 gets a lot more press than -1, and the concept of heterozygosity gets more attention than homozygosity. Concretely the difference between the latter two is rather straightforward. In diploid organisms the genes come in duplicates. If the alleles are the same, then they’re homozygous. If they’re different, then they’re heterozygous. Sex chromosomes can be an exception to this because in the heterogametic sex you generally have only one copy of gene as one of the chromosomes is sharply truncated. This is why in human males are subject to X-linked recessive traits at such a great frequency in comparison to females; recessive expression is irrelevant when you don’t have a compensatory X chromosome to mask the malfunction of one allele.
Of course recessive traits are not simply a function of sex-linked traits. Consider microcephaly, an autosomal recessive disease. To manifest the trait you need two malfunctioning copies of the gene, one from each parent. In other words, you exhibit a homozygous genotype with two mutant copies. I suspect that this particularly common context of homozygosity, recessive autosomal diseases, is one reason why it is less commonly discussed outside of specialist circles: there are whole cluster of medical and social factors which lead to homozygosity which are already the focus of attention. The genetic architecture of the trait is of less note than the etiology of the disease and the possible reasons in the family’s background which might have increased the risk probability, especially inbreeding. In contrast heterozygosity is generally not so disastrous. Even if functionality is not 100%, it is close enough for “government work.” The deleterious consequences of a malfunctioning allele are masked by the “wild type” good copy. The exceptions are in areas such as breeding for hybrid vigor, when heterozygote advantage may be coming to the fore. The details of complementation of two alleles matter a great deal to the bottom line, and the concept of hybrid vigor has percolated out to the general public, with the more informed being cognizant of heterozygosity.
But homozygosity is of interest beyond the unfortunate instances when it is connected to a recessive disease. Like heterozygosity, homozygosity exists in spades across our genome. My 23andMe sample comes up as 67.6% homozygous on my SNPs (which are biased toward ~500,000 base pairs which tend to have population wide variation), while Dr. Daniel MacArthur’s results show him to be 68.1% homozygous across his SNPs. This is not atypical for outbred individuals. In contrast someone whose parents were first cousins can come up as ~72% homozygous. This is important: zygosity is not telling you simply about the state of two alleles, in this case base pairs, it may also be telling you about the descent of two alleles. Obviously this is not always clear on the base pair level; mutations happen frequently enough that even if you carry two minor alleles it is not necessarily evidence that they’re identical by descent (IBD), or autozygous (just a term which denotes ancestry of the alleles from the same original copy). What you need to look for are genome-wide patterns of homozygosity, in particular “runs of homozygosity” (ROH). These are long sequences biased toward homozygous genotypes.