Surprising discovery in the evolution of sex chromosomes! EvolSexChrom project

In mammals, being male or female is dictated by our sex chromosomes. Females have two copies of the X chromosome while males bear an X chromosome and a Y chromosome. The Y chromosome is very small and highly different from the X chromosome. Initially, a long time ago, the X and Y chromosomes were very similar, but they have become more and more different over time, and this has puzzled scientists for years. It has long been thought that this was due to differences between males and females. There are indeed many traits which differ between males and females, such as a lion’s mane, a deer’s antlers or males often being larger. Scientists have therefore formulated the hypothesis that genes with versions that are beneficial only in males could be selected for being linked to the gene determining the male sex on the Y chromosome. Such linkage can occur through chromosomal inversions, so that only male lions develop a mane for example. Inversions indeed prevent recombination, that is, genetic mixing, between the X and Y chromosomes. With time, if multiple genes become progressively linked to the sex-determining gene on the Y chromosome through successive inversions, the X and Y chromosomes will become more and more differentiated. However, no definitive evidence has been found in favor of this hypothesis: indeed, genes controlling male beneficial traits are often NOT on the Y chromosome, being instead hormonally regulated. Furthermore, fungi can also have a pair of differentiated chromosomes that control mating compatibility. Yet, while only plus and minus cells can mate in fungi, they are not associated to male or female functions. The cells of these different mating types, plus and minus, look just identical. Therefore, another mechanism must be able to drive differences between sex chromosomes, that can also apply to fungi. A recent theory shows that this may be driven by deleterious mutations, that is, non-optimal versions of genes that are present at low frequencies in populations, producing non-functional proteins. A deleterious mutation can be sheltered if the homologous chromosome in the same individual codes for a functional protein. Sometimes, chromosomal inversions occur, and they block recombination, that is, they prevent the reshuffling of genetic information with the other homologous chromosome. Half of such inversions carry fewer deleterious mutations than average in the population, thus conferring a survival advantage. Therefore, there will be more and more individuals carrying the inversion generation after generation. However, when it becomes frequent, such an inversion will often be present on the two homologous chromosomes in the same individual. The non-functional gene will not be sheltered anymore by a functional gene. Such individuals with two deleterious copies and no functional one will die young and this will stop the increase in frequency of the chromosomal inversion. Except if, by chance, the inversion with few deleterious mutations also captures the male-determining gene on the Y chromosome. In this case, the inversion will never be in two copies in the same individual because males have a single Y chromosome. The inversion will thus always have intact gene copies sheltering it, the ones on the X chromosome. Such an inversion will therefore always be beneficial, and will reach fixation on the Y chromosome. If this occurs multiple times, several overlapping inversions will fix on the Y chromosome, preventing genetic mixing with the X chromosome, and they will thereby become more and more different. Following recombination suppression, further deleterious mutations will accumulate, which could select for restoring recombination. However, multiple overlapping inversions may accumulate even more rapidly on non-recombining chromosomes, which likely prevent restoring recombination, even if it has become advantageous. This hypothesis is able to explain that differentiated sex chromosomes also occur in fungi, and not only in animals or plants. Several pieces of evidence further support this hypothesis. Indeed, this mechanism can only work in species with two copies of each chromosome. And precisely, the fungi with differentiated mating-type chromosomes are those that carry two copies of each chromosome in most of their cells, while the fungi with a single copy of each chromosome for most of their lifetime, in which deleterious mutations cannot therefore be sheltered, do not show differentiated mating-type chromosomes. The evolution of sex chromosomes may, thus, surprisingly, not be due to differences between males and females, but a consequence of the presence of deleterious mutations in genomes.