Relevance of connexin deafness (DFNB1) to human evolution

Abstract

The connexins are the subunits of a family of proteins that form gap junctions, allowing ions and small molecules to move between adjacent cells. At least four connexins are expressed in the ear, and, although there are known mutations at >100 loci that can cause deafness, those involving DFNB1, in the interval 13q11-q12 containing the GJB2 and GJB6 genes coding for connexins 26 and 30, are the most frequent cause of recessive deafness in many populations. We have suggested that the combined effects of relaxed selection and linguistic homogamy can explain the high frequency of connexin deafness and may have doubled its incidence in this country during the past 200 years. In this report, we show by computer simulation that assortative mating, in fact, can accelerate dramatically the genetic response to relaxed selection. Along with the effects of gene drift and consanguinity, assortative mating also may have played a key role in the joint evolution and accelerated fixation of genes for speech after they first appeared in Homo sapiens 100,000-150,000 years ago.

Figure 1

Computer simulation showing the effects of relaxed selection and assortative mating on the Cx gene, beginning in 1800 with a generation time of 20 years. A, Frequency of Cx homozygotes in the presence (solid line) and absence (dotted line) of assortative mating; B, Frequency of a common recessive deafness gene (Cx) and two rare genes, either linked at 1 cM (Gene A) or unlinked (Gene B) to the Cx locus. A fixed population size of 200,000 and an equal sex ratio were assumed. In B, a mutation-selection balance initially was assumed with frequencies for Cx, A, and B of .01304, .002881, and .002881, respectively. In A and B, the reproductive fitness of the deaf rose from 0 to 1.0 in five generations, whereas assortative mating rose from 0 (random mating) to .9 and remained constant thereafter. To incorporate linguistic homogamy, deaf subjects choosing hearing partners were assumed to select “native signers” who were the offspring of deaf parents, with a probability of .3 by the fifth generation. Such spouses frequently carry multiple nonallelic recessive genes for deafness.