Rebooting the Genome

Abstract

The need for genomes to detect and correct errors has been a major force in evolution, driving DNA to ‘speak in palindromes’ and splitting members of a species into two sexes. Errors associated with DNA mutations or DNA damage may be imperfectly corrected in our bodies (“soma”), but should be better corrected in the germ line. To this end, meiotic recombination repair, in which maternal and paternal genomes are compared, is the last court of appeal. For this ‘rebooting’ of the genome, parental genomes must be neither too similar, nor too disparate. If too similar (inbreeding), differences will not emerge at meiosis in their child’s gonad. If too disparate, an exploratory speciation process (anti-recombination) may initiate, manifest as a healthy, but sterile, child (hybrid sterility). For the initiation of speciation, human females must: (i) differentiate their sex chromosomes (X and X), (ii) differentiate their non-sex chromosomes (22 autosomal pairs), and (iii) activate ‘check-points’ which respond to such differentiations by disrupting meiosis. In contrast human males, being already advanced in the first step due to differentiation of their sex chromosomes (X and Y), have to complete only the latter steps. Thus, the first sign of speciation (incipient speciation), manifest as hybrid sterility, is production of sterile males (Haldane’s rule). Long ago, anti-recombination activity prevented repair of Y-chromosomes, which degenerated, thus loosing many X-chromosome equivalent genes. Human males now have potentially only one dose of many X-chromosome gene products, whereas females have potentially two doses. Dosage compensation in human females, leaving only one X-chromosome active, buffers fluctuations in intracellular protein concentrations between male and female generations. This permits a gene, independently of the sex which may harbor it, to fine-tune the concentration of its protein product to that of other proteins with which it has been traveling through the generations. In this way, collective protein functions, including intracellular self/not-self discrimination, are facilitated. Failure of this may predispose human females to autoimmune disease. By virtue of extensive palindromic sequences, Y chromosomes appear, like some rare ameiotic organisms, capable of in-series error-correction.

What makes hybrid male sterility of great current interest is the increasing evidence that the building blocks of this isolating barrier may be radically different from what we had come to believe. … It is clear that a new paradigm is emerging, which will force us, first, to revised many conclusions … that had gathered almost unanimous agreement, and, second, to try a completely different experimental approach.

Horacio Naveira and Xulio Maside (1998) [1]