published<\/a> Tuesday in the journal Nature Communications, \u201csince the success rate improved slightly with each successive generation.\u201d<\/p>\nIt was all smooth sailing, in fact, until the researchers started cloning their 25th through 27th generations of mice. But by the 58th generation, according to Wakayama\u2019s team, the mice did not even survive for more than a day.<\/p>\n
Thousands of healthy clones <\/p>\n
Scientists have used trichostatin A as an antifungal antibiotic, but it can also inhibit the functioning of certain enzymes in mammals, like mice and also humans. For Wakayama and his team\u2019s purposes, however, the compound also acts as what they call an \u201cepigenetic modification reagent,\u201d suppressing unwanted DNA transcription factors, or the enzymatic proteins that activate pieces of the potentially harmful mutations in a mouse\u2019s genetic code during cloning.<\/p>\n
\u201cMore than 1200 cloned mice were produced from a single original donor mouse,\u201d according to Wakayama, a developmental biologist who works for the University of Yamanashi\u2019s Advanced Biotechnology Center, and his coauthors. And, surprisingly, most fared well before the drop-off.<\/p>\n
\u201cLate-generation clones except [the] last generation that survived to birth were notably healthy,\u201d the team reported, \u201cwith normal lifespans, despite carrying numerous deleterious mutations.\u201d<\/p>\n
These very re-cloned clones, in fact, also developed with most of their reproductive organs healthy and intact, the researchers found, \u201craising the possibility that subsequent generations could be produced via sexual reproduction.\u201d<\/p>\n
Their study suggests that further experimentation with reagents like trichostatin A might further extend cloning deeper into successive generations. They found the compound remained effective, even as they worked with later, more difficult generations of their clones. The success rate for implanting a clone donor cell nucleus into an egg was three times more successful for even 51st generation cloned mice when trichostatin A was used (a 5.4% success rate), as opposed to without the reagent (1.6%).<\/p>\n
A steep drop <\/p>\n
Wakayama\u2019s team did, however, measure some hard facts about the number of natural mutations that emerged between each successive generation of their clones. Each new round of cloned mice acquired about 70 small \u201csingle-nucleotide variants\u201d and about 1.5 additional and more substantial \u201cstructural variants\u201d to their genetic code. While this rate was not out of the ordinary, those structural variations built up over multiple rounds of re-cloning.<\/p>\n
Over time, they found, \u201cthe build-up of harmful variants appears to have outweighed adaptive effects,\u201d without the chromosomal recombination effects of sexual reproduction to filter out the large and potentially harmful genetic variations.<\/p>\n
Here too, there was evidence that even a slight pivot back to sexual reproduction could course-correct these issues. The researchers\u2019 late-generation cloned mice, for example, were born with noticeable abnormalities in their placenta, but when those mice mated naturally, their offspring\u2019s placenta had returned to normal.<\/p>\n
Theories abound for why mammals and other creatures evolved to reproduce sexually, including a case that it helped earlier species protect themselves from parasites<\/a> by offering robust genetic diversity. Wakayama and his group\u2019s own journey to the far end of genetic recloning might suggest mammals need to mate to protect their genome from going stale over time.<\/p>\n","protected":false},"excerpt":{"rendered":"Countless scientists and at least a dozen high-concept sci-fi comedies over the past 30 years have speculated on…\n","protected":false},"author":2,"featured_media":543051,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[32],"tags":[242702,200,21875,79],"class_list":["post-543050","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-clones","tag-genetics","tag-mutation","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/543050","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/comments?post=543050"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/543050\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media\/543051"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media?parent=543050"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/categories?post=543050"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/tags?post=543050"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}