Geneticist Bo Xia asked that question as a child and it was on his mind again a few years ago, while he was recovering from a tailbone injury during his PhD at New York University (NYU) in New York City. Xia and his colleagues now have an answer. The researchers identified a genetic change shared by humans and other apes that might have contributed to their ancestors\u2019 tail loss, some 25 million years ago. Mice carrying similar alterations to their genomes had short or absent tails, the researchers found \u2014 but that insight was hard won. The work was published on 28 February1: nearly 900 days after being submitted to Nature and posted as a preprint, because of extra work needed to develop several strains of gene-edited mice and demonstrate that the genetic changes had the predicted effect. \u201cRespect to the authors,\u201d says Malte Spielmann, a human geneticist at Kiel University in Germany, who reviewed the paper for Nature. \u201cI\u2019m incredibly excited about the fact that they\u2019ve really pulled it off.\u201d The mice with no tails Unlike most monkeys, apes \u2014 including humans \u2014 and their close extinct relatives don\u2019t have tails. Their coccyx, or tailbone, is a vestige of the vertebrae that constitute a tail in other animals. Finding the genetic basis for this trait wasn\u2019t what Xia, now at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, planned to devote his PhD to. But his coccyx injury, sustained during a cab ride, reinvigorated his tail curiosity. On a hunch, Xia decided to examine a gene famous for its role in tail development. In 1927, Ukrainian scientist Nadine Dobrovolskaya-Zavadskaya described a strain of short-tailed lab mouse that, she proposed, carried a mutation in a gene called T, the human equivalent of which is now known as TBXT. \u201cYou\u2019ll find this gene in your first Google search,\u201d says Xia. A quick search of geneticists\u2019 version of Google \u2014 the genome browser maintained by the University of California, Santa Cruz \u2014 showed that humans and other apes carry a DNA insertion in TBXT that other primates with tails, such as monkeys, don\u2019t have. Gene splice In a preprint2 posted on bioRxiv in September 2021, Xia and his colleagues showed that the ape insertion can lead to a shortened form of the protein that TBXT encodes. They proposed that that the shortening occurs after the gene is transcribed into messenger RNA, and when multiple protein-encoding segments of the gene transcript get spliced together. Gene-edited mice with one clipped copy of the mouse version of TBXT had a range of tail defects. In some, the tail was shortened or missing completely; in others it was kinked or extra-long. The findings attracted dozens of news stories, but the preprint didn\u2019t show that the ape genetic insertion, when introduced into mouse version of TBXT, could cause tail loss, says Spielmann. \u201cThey hadn\u2019t done the main experiment.\u201d Those experiments were under way when the paper was submitted to Nature, says Itai Yanai, a systems biologist at NYU who co-led the study. They ended up showing that the genetic insertion, when transplanted into the mouse genome, didn\u2019t lead to very high levels of the shortened version of the protein. The resulting mice had normal tails. The researchers also engineered mice with a different insertion in the mouse version of TBXT. Serendipitously, this caused the gene to be mis-spliced in the same way as it is in humans. Mice carrying this insertion were born with short or entirely missing tails. Tree swingers Yanai says the extra experiments added rigour to the study, even if the overall conclusion is largely the same. \u201cMaking all those mouse lines is a major undertaking,\u201d says Miriam Konkel, an evolutionary geneticist at Clemson University in South Carolina. \u201cI really felt for those authors when I saw what they did.\u201d \u201cIt turned out to be a much stronger paper,\u201d adds Spielmann. \u201cThey clearly show that this change contributes to tail loss. But it\u2019s not the only one.\u201d The researchers analysed 140 genes involved in tail development and identified thousands of genetic changes unique to apes that might also have played a part in tail loss. \u201cI\u2019m really excited to see work being done on the genetic mechanisms underpinning tail loss and length reduction,\u201d says Gabrielle Russo, a biological anthropologist at Stonybrook University in New York. Xia\u2019s team says that tail loss might have contributed to apes\u2019 ability to walk upright and to them spending less time in trees, but Russo isn\u2019t so sure. Fossils suggest that early apes moved on four legs like tree-dwelling monkeys, and that bipedality evolved millions of years later. Apes aren\u2019t the only primates without tails: mandrills, some macaques and the big-eyed nocturnal creatures called lorises all lack tails, suggesting that the trait evolved multiple times. \u201cProbably, there are multiple ways of losing a tail during development. Our ancestors chose this way,\u201d Xia says.<\/p>\n","protected":false},"excerpt":{"rendered":"
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