Evolution of X‐Chromosome Inactivation

AbstractX‐chromosome inactivation is a transcriptional silencing of one of the two X chromosomes that occurs in females of marsupial and eutherian mammals. The process arose and developed as a part of dosage compensation mechanism during differentiation of mammalian X and Y chromosomes. X inactivation started from being imprinted and unstable in marsupials and then was transformed to random and stable in eutherians. The transformation included replacement of the key noncoding nuclearribonucleic acidmaster switch genersxtoxist, and emergency of the X‐inactivation centre responsible for random choice of one of the two X chromosomes. Presumably, further involvement of thexist‐dependent repressive histone modifications together withdeoxyribonucleic acidmethylation and enrichment of the X chromosome with LINE1 mobile elements, allowed for more efficient spread and maintenance of an inactive state and has made the X‐chromosome inactivation process more complete and stable. During eutherian evolution, X‐chromosome inactivation mechanisms have tended to accumulate the taxon‐ and species‐specific differences.Key Concepts:X‐chromosome inactivation emerged as part of dosage compensation mechanism caused by differentiation of mammalian X and Y chromosomes.X‐chromosome inactivation is unique for marsupial and eutherian mammals.X‐chromosome inactivation has evolved from imprinted, incomplete, and unstable to random, complete, and efficiently maintained.The long noncoding nuclear RNA controlling X‐chromosome inactivation, initiallyrsxin marsupials, has been replaced forxistin eutherians.The noncoding nuclear RNA genexist, responsible for initiation of inactivation in eutherians, emerged from a protein coding gene and a set of mobile elements.Xistand the surrounding genes regulating its expression have formed the inactivation centre that regulate a random choice of one of the two X chromosomes to be transcriptionally silent.Presumably, the main steps leading to complete and stable X‐chromosome inactivation are involvement of thexist‐dependent repressive histone modifications in gene rich clusters together with DNA methylation of the promoters and enrichment of X chromosome with the mobile elements LINE.During eutherian evolution, X‐chromosome inactivation mechanisms mainly accumulated taxon‐ and species‐specific differences.