Organization and evolution of the marsupial X chromosome

Abstract

Marsupial genomics and genetics provide invaluable data for comparative analysis because these mammals are distantly related cousins of humans and other eutherian mammals (∼148 million years), but they are more closely related to eutherians compared to monotremes (∼166 million years) and birds (∼310 million years). This divergence time places them uniquely on the phylogenetic tree whereby comparative gene mapping and genome sequences of marsupials enable us to trace the evolution of the therian X chromosome. It is shown by comparative gene mapping that the marsupial X chromosome is homologous to the long arm and pericentric region of the short arm of the human X chromosome (X conserved region). However, it is homologous to autosomes in the platypus and the chicken, suggesting that a novel XY system evolved in therian mammals after they diverged from monotremes 166 million years ago but before marsupials diverged from eutherians 148 million years ago. Apart from the X conserved region, eutherian mammals have an autosomal addition on the X chromosome (X added region) since their divergence from marsupials. Although the marsupial X chromosome is similar in composition to that of the eutherian X chromosome, it has accumulated numerous rearrangements, has become GC rich and has acquired a higher synonymous substitution rate since divergence of marsupial and eutherian mammals. Similarly, the marsupial X chromosome undergoes X inactivation like eutherian mammals, but the mechanisms, which regulates X inactivation, is very different from that observed in eutherian mammal, and may be the ancestral state. The XIST gene responsible for X inactivation in eutherian mammals is absent from the marsupial lineage suggesting that the evolution of XIST in early eutherians set up selection for accumulation of LINE sequences that aided the spread of X inactivation. Unlike the LINE accumulation on the eutherian X chromosome, the marsupial X has accumulated and expanded a microRNA family that could be involved in the marsupial X inactivation. This chapter provides a comprehensive review of the organization and evolution of the marsupial X chromosome and the implications this may have for X inactivation.