A chromosome predisposed for sex

A genome sequence for the flatworm Schmidtea mediterranea reveals a chromosome that might be primed to become a sex chromosome. The finding offers a remarkable chance to study the evolution of sex determination.

Yuying Lin & Judith E. Mank | June 1, 2022

There is an interesting dichotomy in the fact that sperm and eggs are broadly similar across animals, and yet the mechanism by which sex is determined varies enormously1. For instance, some animals are hermaphroditic, producing both eggs and sperm, either simultaneously or sequentially. Many other animals spend their entire lives as either females or males. In this case, sex can be determined by ecological factors such as temperature or demography, or by sex chromosomes. This diversity makes sex determination challenging to understand – a problem compounded by the fact that sex-determination mechanisms often evolve rapidly, and can vary even between closely related species2Writing in Nature, Guo et al.3 offer clues to how animals might transition from hermaphroditism to having separate sexes using sex chromosomes, with an unexpected twist to events.

The evolution of sex chromosomes has puzzled researchers since 1905, when the geneticist Nettie Stevens first described these chromosomes in meal worms4. It has become clear that, despite having arisen independently many times in plants and animals, sex chromosomes generally have similar key characteristics5, most notably a male-limited region on the Y chromosome that contains at least one sex-determining gene crucial for male gonad development. Most chromosomes exchange material through a process called recombination during the meiotic cell divisions that form sperm and eggs. By contrast, the male-limited region of the Y chromosome has stopped recombining with the other member of its pair, the X chromosome.

Theoretical models posit that a sex-determining gene that directs testis development emerges first on an otherwise normal chromosome, and recombination is then suppressed in the chromosomal region around it6. As recombination suppression evolves, the Y chromosome becomes isolated from the X, and so X and Y chromosomes slowly become more and more different from one another (Fig. 1a). The non-recombining portion of the Y chromosome, often referred to as a haplotype, is inherited as a single unit from father to son.

Figure 1

Figure 1 | Two routes to sex chromosomes. a, Chromosomes exchange genetic material through recombination (indicated by overlapping regions) during the cell divisions that produce eggs and sperm. The conventional model of X–Y sex-chromosome evolution posits that a gene that directs development of male embryos emerges on one chromosome, and that — over evolutionary timescales — recombination is suppressed around the gene, ensuring that it is always inherited from father to son as part of a proto-Y chromosome. Finally, the Y chromosome diverges from the other member of its pair, dubbed X. b, Guo et al.3 propose an alternative model of sex-chromosome evolution for the flatworm Schmidtea mediterranea. First, two versions of chromosome 1 stop recombining, apart from at their tips. After this, one diverges from the other to make two different ‘haplotypes’ (dubbed J and V). Finally, the male-determining gene emerges on one haplotype, and X and Y chromosomes are formed.

Guo et al. present a different order of events. Studying the genome of the hermaphroditic flatworm Schmidtea mediterranea, the group observed two large haplotypes, named J and V, on different copies of chromosome 1. In individuals with one copy of each haplotype (heterozygotes), the two copies of chromosome 1 form a ring during meiotic cell division, connected and recombining only at the ends. The J and V haplotypes, which make up the central portion of each chromosome, do not recombine with each other, just as the X and Y chromosomes do not recombine. Also like the X and Y, the S. mediterranea haplotypes are genetically distinct from one another in both DNA sequence and the expression of many genes.

Non-recombining, genetically diverged haplotypes are not uncommon in genomes, but what is unusual about the S. mediterranea haplotypes is that the region contains many of the genes that underlie both male and female gonad development. It could easily be imagined that just a few mutations in these genes could produce a haplotype that is necessary for one sex. For instance, a mutation in one haplotype that prevents expression of a gene essential for ovary development would make that haplotype male-determining, similar to the Y chromosome. The organism would then begin the transition from being hermaphroditic to having two separate sexes, determined by sex chromosomes.

For S. mediterranea, then, the events that might lead to the evolution of sex chromosomes started with the arrest of recombination, followed by the divergence of haplotypes. For sex-chromosome evolution to progress, one haplotype must go on to become sex-specific through the emergence of a sex-determining gene (Fig. 1b). This is different from the standard model for the evolution of sex determination, but if we have learnt anything about sex-chromosome evolution, it is that there are multiple evolutionary routes7 and no single model explains them all.

The S. mediterranea haplotypes potentially offer a remarkable system for studying the genes involved in the evolution of sex determination. Interestingly, Guo and colleagues propose that a fully hermaphroditic species has a region of the genome that is predisposed to being a sex chromosome, with no apparent evolutionary reason for it. What we do not know, however, is whether this region would actually become a sex chromosome. It might or it might not, and there are many sex-determining genes on other chromosomes that could evolve into sex chromosomes through the conventional model.

In support of the idea that chromosome 1 can evolve into a sex chromosome, the authors point to evolutionary conservation of gene content between the chromosome 1 haplotypes and the sex chromosomes in a distant relative, Schistosoma mansoni — the only flatworm for which a full genome sequence that has sex chromosomes is available. Broader comparative work could determine whether these haplotypes comprise sex chromosomes in other species. Genetic manipulation of the haplotypes in S. mediterranea could also be used to engineer chromosome 1 to become proper sex chromosomes. Such avenues offer exciting ways to determine the prevalence and mechanism of this route to sex determination.

 

This commentary on MBI member’s, Leonid Kruglyak, paper “Island-specific evolution of a sex-primed autosome in a sexual planarian” was originally published in Nature.

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