Haploid genomes illustrate epigenetic constraints and gene dosage effects in mammals

Martin Leeb,Anton Wutz

doi:10.1186/1756-8935-6-41

Abstract

Sequencing projects have revealed the information of many animal genomes and thereby enabled the exploration of genome evolution. Insights into how genomes have been repeatedly modified provide a basis for understanding evolutionary innovation and the ever increasing complexity of animal developmental programs. Animal genomes are diploid in most cases, suggesting that redundant information in two copies of the genome increases evolutionary fitness. Genomes are well adapted to a diploid state. Changes of ploidy can be accommodated early in development but they rarely permit successful development into adulthood. In mammals, epigenetic mechanisms including imprinting and X inactivation restrict haploid development. These restrictions are relaxed in an early phase of development suggesting that dosage regulation appears less critical. Here we review the recent literature on haploid genomes and dosage effects and try to embed recent findings in an evolutionary perspective.

Highlights

Sequencing projects have revealed the information of many animal genomes and thereby enabled the exploration of genome evolution
Haploid genomes in insects and mites The information for the development of an organism is encoded in its genomic DNA sequence
Embryos with impaired dosage compensation due to a mutation in the Xist gene develop beyond implantation [39,60]. These findings indicate that pre-implantation development is largely independent of dosage compensation and the presence of a bi-parental complement of imprints

Summary

Conclusions

The ability to derive haploid ES cells might be facilitated by a distinct developmental state. A recent comparison of serum and 2i culture has identified surprisingly large differences in gene expression [74] These observations suggest that regulatory networks in ES cells are robust to disturbances in gene expression patterns. Development of haploid embryos is affected by requirements for imprinted gene expression and dosage compensation. Interference with the mechanism of X upregulation could potentially be considered for reducing the X-linked gene dosage in haploid cells. In contrast to tumor cells, relative gene dosage imbalances are more detrimental to survival of untransformed cells than haploidy This suggests that reduction of a diploid to a near haploid karyotype in a single instance or rapid succession of manipulations would be required. Future research will contribute to methods for establishing haploid cells and rebalancing gene dosage that could lead to an increased developmental potential.

Normark BB

20. Graham CF