the transfer of epigenetic activity along long genomic stretches. decreased transcription of both hermaphroditic xs by half other species that do not follow the previously discussed conventions of xx females and xy males must find alternative ways to equalize x-linked gene expression among differing sexes. for example, in caenorhabditis elegans (or c. elegans), sex is determined by the ratio of x chromosomes relative to autosomes; worms with two x chromosomes (xx worms) develop as hermaphrodites, whereas those with only one x chromosome (xo worms) develop as males. this system of sex determination is unique, because there is no male specific chromosome, as is the case in xx/xy sex determination systems. however, as is the case with the previously discussed mechanisms of dosage compensation, failure to express x-linked genes appropriately can still be lethal. in this xx/xo sex determination system, gene expression on the x chromosome is equalized by downregulating expression of genes on both x chromosomes of hermaphroditic xx organisms by half. in these xx organisms, the dosage compensation complex (dcc) is assembled on both x chromosomes to allow for this tightly regulated change in transcription levels. the dcc is often compared to the condensin complex, which is conserved across the mitotic and meiotic processes of many species. this complex is crucial to the condensation and segregation of chromosomes during both meiosis and mitosis. because data substantiates the theory that dosage compensation in other species is caused by chromatin-wide modifications, many theorize that the dcc in particular functions similar to the condensin complex in its ability to condense or remodel the chromatin of the x chromosome. the role of the dcc in this form of dosage compensation was postulated by barbara j. meyer in the 1980s, and its individual components and their cooperative function were later parsed out by her lab. notably, in 1999, data from meyer's lab showed that sdc-2 is a particularly important transcriptional factor for targeting the dcc to the x chromosome and for assembling dcc components onto the x chromosomes in xx embryos. more recently, meyer's lab has shown that proteins known as x-linked signal elements (xses) operate in concert with sdc-2 to differentially repress and activate other genes in the dosage compensation pathway. by selectively mutating a panel of genes hypothesized to contribute to dosage compensation in worms, meyer's group demonstrated which xses specifically play a role in determining normal dosage compensation. they found that during embryonic development, several x-linked genes—including sex-1, sex-2, fox-1, and ceh-39—act in a combinatorial fashion to selectively repress transcriptional activity of the xol-1 gene in hermaphrodites. xol-1 expression is tightly regulated during early development, and is considered the most upstream gene in sex determination of c. elegans. in fact, xol-1 is often referred to in the literature as the master sex regulatory gene of c. elegans. xx c. elegans embryos have much lower xol-1 expression than their xo counterparts, resulting from overall increases in the amount of sex-1, sex-2, ceh-39, and fox-1 transcription produced in the female embryos. this consequent decrease in xol-1 expression then allows higher sdc-2 expression levels, which aids in the formation and function of the dcc complex in the xx hermaphroditic worms, and in turn results in equalized expression of x-linked genes in the hermaphrodite. though all of the above-mentioned xses act to reduce xol-1 expression, experimentally reducing expression levels of these individual xses has been shown to have a minimal effect on sex determination and successful dosage compensation. this could be in part because these genes encode different proteins that act cooperatively rather than in an isolated fashion; for example, sex-1 is a nuclear hormone receptor, while fox-1 is an rna-binding protein with properties capable of inducing post-transcriptional modifications in the xol-1 target. however, reducing the level of more than one xse in different combinational permutations seems to have an additive effect on ensuring proper sex determination and resultant dosage compensation mechanics. this supports the hypothesis that these xses act together to achieve the desired sex determination and dosage compensation fate. thus, in this model organism, the achieved level of x-chromosome expression is directly correlated to the activation of multiple xses that ultimately function to repress xol-1 expression in a developing worm embryo. a summary of this c. elegans mechanism of dosage compensation is illustrated below. other species-specific methods the zz/zw sex system is used by most birds, as well as some reptiles and insects. in this system the z is the larger chromosome so the males (zz) must silence some genetic material to compensate for the female's (zw) smaller w chromosome. instead of silencing the entire chromosome as humans do, male chickens (the model zz organism) seem to engage in selective z silencing, in which they silence only certain genes on the extra z chromosome. thus, male chickens express an average of 1.4-1.6 of the z chromosome dna expressed by female chickens. the z chromosome expression of male zebra finches and chickens is higher than the autosomal expression rates, whereas x chromosome expression in female humans is equal to autosomal expression rates, illustrating clearly that both male chickens and male zebra finches practice incomplete silencing. few other zz/zw systems have been analyzed as thoroughly as the chicken; however a recent study on silkworms revealed similar levels of unequal compensation across male z chromosomes. z-specific genes were over-expressed in males when compared to females, and a few genes had equal expression in both male and female z chromosomes. in chickens, most of the dosage compensated genes exist on the zp, or short, arm of the chromosome while the non-compensated genes are on the zq, or long, arm of the chromosome. the compensated (silenced) genes on zp resemble a region on the primitive platypus sex chromosome, suggesting an ancestor to the xx/xy system. birds the sex chromosomes of birds evolved separately from those of mammals and share very little sequence homology with the xy chromosomes. as such, scientists refer to bird sex chromosomes as a zw sex-determining system, with males possessing two z chromosomes, and females possessing one z chromosome and one w. thus, dosage compensation in birds could be hypothesized to follow a pattern similar to the random x-inactivation observed in most mammals. alternatively, birds might show decreased transcription of the two z chromosomes present in the male heterogametic sex, similar to the system observed in the two hermaphrodite x chromosomes of c. elegans. however, bird mechanisms of dosage compensation differ significantly from these precedents. instead, male birds appear to selectively silence only a few genes along one of their z chromosomes, rather than randomly silencing one entire z chromosome. this type of selective silencing has led some people to label birds as “less effective” at dosage compensation than mammals. however, more recent studies have shown that those genes on the z chromosome which are not inactivated in birds may play an important role in recruiting dosage compensation machinery to the z chromosome in zz organisms. in particular, one of these genes, scii has been demonstrated to be an ortholog of xol-1, the master sex regulator gene in c. elegans. thus, the function of the selective silencing may be to spare dosage compensation of genes crucial for sex determination of homologous pairing. while the epigenetic mechanisms behind dosage compensation in birds are poorly understood, especially in comparison to the well-studied mechanisms of dosage compensation in humans and drosophila, several recent studies have revealed promising sequences. one example is mhm (male hypermethylated) rna, an xist-like long noncoding rna that is expressed only in female chickens (zw). it is associated with female-specific hyper-acetylation of lysine 16 on histone 4 near the mhm locus on the z chromosome. this mhm locus is heavily studied as a site of dosage compensation because male z chromosomes are hypermethylated and thus underexpress genes in this area in comparison to female z chromosomes which are hyperacetylated and overexpress these genes. there has been debate on whether the mhm locus constitutes dosage compensation, however, since scientists claim that even if the mhm locus has been found to have significantly greater expression in females than in males, it could not even be considered to be a dosage compensation mechanism since it does not balance gene dose between the z chromosome and autosomes in the heterogametic sex. similar to mammals, chickens seem to use cpg islands (segments of cytosine-phosphate-guanine that are more readily methylated and silenced than other dna segments) to regulate gene expression. one study found that cpg islands were found primarily in compensated areas of the z chromosome—areas that are differentially expressed in male and female chickens. thus it is likely that these cpg islands are locations where genes on the male z chromosome are methylated and silenced, but which stay functional on the female z chromosome. monotremes platypus, a type of monotreme monotremes are a class of basal mammals that also lay eggs. they are an order of mammals that includes platypuses and four species of echidna, all of which are egg-laying mammals. while monotremes use an xx/xy system, unlike other mammals, monotremes have more than two sex chromosomes. the male short-beaked echidna, for example, has nine sex chromosomes—5 xs and 4 ys, and the male platypus has 5 xs and 5 ys. platypuses are a monotreme species whose mechanism of sex determination has been extensively studied. there is some contention in academia about the evolutionary origin and the proper taxonomy of platypuses. a recent study revealed that four platypus x chromosomes, as well as a y chromosome, are homologous to some regions on the avian z chromosome. specifically, platypus x1 shares homology with the chicken z chromosome, and both share homology with the human chromosome 9. this homology is important when considering the mechanism of dosage compensation in monotremes. in 50% of female platypus cells, only one of the alleles on these x chromosomes is expressed while in the remaining 50% multiple alleles are expressed. this, combined with the portions that are homologous to chicken z and human 9 chromosomes imply that this level of incomplete silencing may be the ancestral form of dosage compensation. regardless of their ambiguous evolutionary history, platypuses have been empirically determined to follow an xy sex-determination system, with females possessing five pairs of x chromosomes as the homogametic sex, and males possessing five x and five y chromosomes as the heterogametic sex. because the entire genome of the platypus has yet to be completely sequenced (including one of the x chromosomes), there is still continued investigation as to the definitive mechanism of dosage compensation that platypuses follow. research from the laboratory of jennifer graves used qpcr and snp analysis of bacs containing various genes from x chromosomes in order to find whether multiple alleles for particular x-linked genes were being expressed at once, or were otherwise being dosage compensated. her group found that in female platypuses, some x-linked genes only expressed an allele from one x chromosomes, while other genes expressed multiple alleles. this appears to be a system similar to the selective silencing method of dosage compensation observed in birds. however, about half of all x-linked genes also seemed to stochastically express only one active copy of said gene, alluding to the system of random x-inactivation observed in humans. these findings suggest that platypuses may employ a hybrid form of dosage compensation that combines feature from mammals as well as birds. understanding the evolution of such a system may have implications for solidifying the true ancestral lineage of monotremes. plants in addition to humans and flies, some plants also make use of the xx/xy dosage compensation systems. silene latifolia plants are also either male (xy) or female (xx), with the y chromosome being smaller, with fewer genes expressed, than the x chromosome. two separate studies have shown male s. latifolia expression of x-linked genes to be about 70% of the expression in females. if the s. latifolia did not practice dosage compensation, the expected level of x-linked gene expression in males would be 50% that of females, thus the plant practices some degree of dosage compensation but, because male expression is not 100% that of females, it has been suggested that s. latiforia and its dosage compensation system is still evolving. additionally, in plant species that lack dimorphic sex chromosomes, dosage compensation can occur when aberrant meiotic events or mutations result in either