Opossum X Chromosome Sequence Reveals Steps In The Evolution Of The Human X And X Inactivation

Matthew J Wakefield^1,2,* Tarjei S Mikkelsen³ Andrew J Gentles⁴ Jennifer A M Graves⁵ John M Greally⁶ The Opossum Genome Sequencing Consortium³

¹The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050, Australia

²The ARC Centre for Kangaroo Genomics

³The Broad Institute of Harvard and MIT, Boston, MA, USA.

⁴Radiology Department, Stanford University and Genetic Information Research Institute, CA, USA

⁵ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, Australian National University, Canberra, ACT, Australia.

⁶Albert Einstein College of Medicine, Bronx, NY, USA.

Keywords:

Comparative GenomicsEpigeneticsBioinformaticsEvolutionary GeneticsFunctional GenomicsRNAi and non-coding DNA

Sequence analysis of the X chromosome from the marsupial Monodelphis domestica defines the ancient region of the human X, and many marsupial-specific inversions. An XIST gene is absent and accumulation of L1 long interspersed nuclear elements (L1 LINEs) on the X chromosome is significantly less than in human.

These observations support the theory that the X inactivation centre and XIST evolved in the eutherian ancestor only 180-100MYA, modifying a pre-existing paternal X inactivation system.

The presence of the XIST gene in eutherian mammals correlates with fewer inversions and increased accumulation of L1 elements, suggesting selection against rearrangements that disrupt the spread of X inactivation from a centre, and exaptation of a pre-existing repeat distribution into the eutherian X inactivation pathway.

Mikkelsen et al (2007) Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 477:167-77.

Hore et al (2007) XIST is absent from the X chromosome, and its flanking region is disrupted in non-placental mammals. Chromosome Research 15:147-61