Periodic Reporting for period 2 - GermlineChrom (Evolutionary origin and impact of germline-restricted chromosomes)
Période du rapport: 2023-04-01 au 2024-09-30
Programmed DNA elimination is the fascinating yet enigmatic phenomenon which removes genome fragments or entire chromosomes during the embryonic development of a wide range of animals such as nematodes, lampreys, and songbirds. In each new generation of these animals, the same parts of the genome of the immortal germline are eliminated to give rise to the mortal somatic line. However, it remains unclear how and why programmed DNA elimination evolved in so many animal groups, and how widespread this phenomenon really is across the Tree of Life.
Using the germline-restricted chromosome (GRC) of songbirds as a unique study system for programmed DNA elimination, the objectives of this multidisciplinary project are to resolve the evolution and function of the GRC through its study across four levels of organization, within populations, between populations, between species, and across development. The interdisciplinary synthesis of these results promises to deepen not only our knowledge of where and why programmed DNA elimination exists, but also our understanding of the genetic and mechanistic basis of human diseases such as abnormal chromosome elimination or cancer.
Using the germline-restricted chromosome (GRC) of songbirds as a unique study system for programmed DNA elimination, the objectives of this multidisciplinary project are to resolve the evolution and function of the GRC through its study across four levels of organization, within populations, between populations, between species, and across development. The interdisciplinary synthesis of these results promises to deepen not only our knowledge of where and why programmed DNA elimination exists, but also our understanding of the genetic and mechanistic basis of human diseases such as abnormal chromosome elimination or cancer.
By studying the germline genomes of nearly thirty representatives of songbirds and relatives, we have found evidence that not only songbirds, but all Passeriformes likely exhibit GRCs, making this a widespread phenomenon among two thirds of all 10,500 bird species. The single origin of the GRC was followed by dynamic gain and loss of developmental genes copied from the rest of the genome (Ruiz-Ruano et al., manuscript in preparation). On more recent evolutionary timescales, we found evidence for occasional paternal inheritance of the GRC in zebra finch populations (Pei et al. 2022, PNAS; Pei et al., manucript in preparation), which explains unexpectedly low levels of genetic variation on the GRC between zebra finch populations (Chen et al., manuscript in preparation). Finally, ongoing analyses of GRC expression and elimination across zebra finch embryo and gonad development have provided key candidate genes for GRC function and narrowed down the likely timepoint of GRC elimination (Vontzou et al., manuscripts in preparation).
This project has pioneered evolutionary analyses of GRCs across species and populations not just of passerine birds but of any organism, as well as the multi-omic analysis of GRC expression and elimination across embryo and gonad development not just of zebra finch but of any organism. We expect to pinpoint the timing and mechanism of elimination until the end of the project, as well as provide answers regarding the origin, inheritance, and function of this widespread form of programmed DNA elimination in passerine birds.