suggested that this benefits retroviruses because p53's mechanism provides a rapid induction of transcription, which leads to the exit of viral RNA from the host cell. Finally, the insertion of ERVs or ERV elements into genic regions of host DNA, or overexpression of their transcriptional variants, has a much higher potential to produce deleterious effects than positive ones. Their appearance into the genome has created a coevolutionary dynamic that proliferated the duplication and expansion of repressor genes. The most clear-cut example of this involves the rapid duplication and proliferation of tandem zinc-finger genes in mammal genomes. Zinc-finger genes, particularly those that include a KRAB domain, exist in high copy number in vertebrate genomes, and their range of functions are limited to transcriptional roles. It has been shown in mammals, however, that the diversification of these genes was due to multiple duplication and fixation events in response to new retroviral sequences or their endogenous copies to repress their transcription. Role in disease The majority of ERVs that occur in vertebrate genomes are ancient, inactivated by mutation, and have reached genetic fixation in their host species. For these reasons, they are extremely unlikely to have negative effects on their hosts except under unusual circumstances. Nevertheless, it is clear from studies in birds and non-human mammal species including mice, cats and koalas, that younger (i.e., more recently integrated) ERVs can be associated with disease. The number of active ERVs in the genome of mammals is negatively related to their body size, suggesting a contribution to Peto's paradox through cancer pathogenesis. This has led researchers to propose a role for ERVs in several forms of human cancer and autoimmune disease, although conclusive evidence is lacking. Neurological disorders In humans, ERVs have been proposed to be involved in multiple sclerosis (MS). A specific association between MS and the ERVWE1, or "syncytin", gene, which is derived from an ERV insertion, has been reported, along with the presence of an "MS-associated retrovirus" (MSRV), in patients with the disease. Human ERVs (HERVs) have also been implicated in ALS and addiction. In 2004 it was reported that antibodies to HERVs were found in greater frequency in the sera of people with schizophrenia. Additionally, the cerebrospinal fluid of people with recent onset schizophrenia contained levels of a retroviral marker, reverse transcriptase, four times higher than control subjects. Researchers continue to look at a possible link between HERVs and schizophrenia, with