Periodic Reporting for period 1 - Xspect (X-chromosome driven speciation through testes-expressed genes: comparative population genomics meets scRNA analysis in primates)
Periodo di rendicontazione: 2022-10-01 al 2025-03-31
A new biological species forms when a species splits into two populations that gradually become more distinct and, after sufficient time, become reproductively isolated, i.e. matings between the two forms can not produce fertile offspring. However, how this process plays out at the molecular level is an open question. In mammals, sex chromosomes play a strong role. Males that carry an X and a Y chromosome are always the sex where hybrids first become infertile. This indicates a rapid accumulation of incompatibilities between the X and the Y in diverging populations. The purpose of the project is to identify such incompatibilities. The study system is the primates that constitute about 500 species. Many species can still (rarely) hybridise and produce offspring, sometimes with reduced male fertility. To identify emerging incompatibilities between the X and the Y, we study the evolution of genes expressed during spermatogenesis. We need to get testis samples from many individuals of many species and use single-cell approaches to understand changes to gene regulation. The hypothesis is that sex chromosomes can easily be hi-jacked by selfish genetic elements favouring the transmission of either the X or the Y in spermatogenesis. This process is called meiotic drive and is expected to cause rapid spread of these selfish elements, a transient change in the sex ratio of offspring, even if they harm spermatogenesis to some extent. Meiotic drive is known in other species, such as Drosophila and mouse, but has not yet been demonstrated in primates. We wish to use comparative evolutionary analysis of genes in spermatogenesis, identify potential drivers, and study their behaviour in natural hybrid zones of different primate species. The goal is to demonstrate a general mechanism of speciation.
The work performed so far has been on 1. generating genomics resources for more than 230 primate species, 2. developing new statistical frameworks to investigate past speciation events, 3. acquiring a large set of testis samples from different primate species, 4. performing large scale single cell transcriptomics experiments, and 5. Study the flow of genes in natural hybrid zones, so far of baboons and macaques. These are the five main ingredients of the overall project. The goal is to integrate the findings to test the overall hypothesis of the project and provide a fuller understanding of the drivers of primate speciation. The genomic resources have been generated in a large international effort to sequence 800 individuals from 233 species of primates, and the analysis of these has been published in 2023 and 2024. The first statistical framework suitable for analysis of past speciation processes was developed and published in 2023, and it will be applied to many speciation events in ongoing studies. The collection of testis samples is ongoing through collaborations with European Zoos (endorsed by the European Association of Zoos and Aquaria (EAZA)), and has so far resulted in samples from 102 individuals from 33 primate species. The collection effort will continue for the rest of the project. Single nuclei transcriptomics has been performed for 15 individuals of 13 different species and is currently being analysed. A specific effort to generate very high quality data by cell sorting has been developed and will be used for future generation of data from more of the samples (27 samples are planned within the next 6 months). New approaches to infer the quality of spermatogenesis from image analysis of cross-sections of testis have been developed and applied to 12 species. Studies of barriers to gene flow have been performed in baboons and macaques hybridisation zones, and preliminary results suggest strong barriers are associated with specific regions of the X chromosomes. The major obstacles has been in generating high quality single cell transcriptomics data, but these have been solved by sorting nuclei prior to single-nuclei experiments.
The genomic resources generated and published are unprecedented in primates and were only possible by participation in a large, now published, international effort. The new statistical approach to studying past speciation processes is published and has received acclaim among scientific peers for its novelty. Little is known about the efficiency of spermatogenesis in primate species except for humans and macaques, and the single-cell transcriptomics data generated is, therefore, unique and offers an entirely new approach to understanding spermatogenesis and its relation to speciation. Preliminary results on natural selection across the primate phylogeny in relation to different breeding systems strongly suggest that the efficiency of natural selection is related to the amount of sperm competition (multiple mating of females), which has not been demonstrated before and sets strong predictions for which species should experience most cases of meiotic drive. Meiotic drivers have not yet been demonstrated since this will require further analysis of the available and planned experiments