BEIJING, June 6 (Zhongxin Net) -- As one of the twelve Chinese zodiac signs, snakes are a widely known and widely distributed type of reptile, and the idiom "painting snakes to add feet" warns people that snakes are footless (limbless) animals. However, how did snakes originate? Were there any limbs initially? If so, how was it lost during evolution? These questions have long attracted the attention of the academic community, and the public is also quite curious.

Evolution of blind snakes and infrared sensing snakes. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

Evolution of the snake sensory system. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

It evolved from cave lizards about 1 million years ago

The team of Li Jiatang, a researcher at the Chengdu Institute of Biology, Chinese Academy of Sciences (Chengdu Institute of Biology, Chinese Academy of Sciences), systematically explained the genetic mechanism of the origin and special phenotypic evolution of snakes by selecting snakes of different clades from the world, combined with large-scale multi-omics technology and gene editing.

Evolutionary characteristics of the snake genome. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

Based on the chromosome-level snake genome dataset, the research team has successfully constructed the most powerful snake phylogenetic framework to date, indicating that snakes originated in the Early Cretaceous period about 1 million years ago, evolved from cave lizards, and are also specialized types of missing limbs in quadrupeds.

This important research result paper completed by Chinese scientists that comprehensively reveals the mystery of the origin and evolution of snakes was published online in the internationally renowned academic journal Cell on the night of June 6, Beijing time, and will be officially published as a cover paper in Volume 19, Issue 7 on July 6.

Researcher Li Jiatang, the corresponding author of the paper, pointed out that based on a variety of high-throughput genome sequencing technologies, the research team assembled and spliced 14 high-quality reference genomes (12 of which are chromosomal level) from scratch, representing 12 different snakes. At the same time, combined with nearly 200 multi-species and multi-tissue transcriptome sequencing data and gene editing and other functional experiments, the genetic mechanism of the origin and phenotypic evolution of snakes was deeply explored.

Important genetic mechanisms such as loss of limbs, body lengthening, and asymmetric development of internal organs in snakes. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

The study suggests that snakes originated in the Early Cretaceous period, about 1 million years ago, and that the most recent common ancestor with the closest relatives (monarch snake lizard, Komodo monitor lizard, etc.) is a "sister" relationship, suggesting that the ancestor of the snake may have been some kind of lizard. In the process of evolution, snakes first differentiated into a group of blind snakes, and after the mass extinction event at the Cretaceous-Early Tertiary boundary about 18 million years ago, snake species exploded.

Solve the evolutionary mysteries such as the loss of limbs and the extension of the body

Li Jiatang said that at present, there are about 4000,<> species of snakes known in the world, widely distributed in the land and sea of all continents except Antarctica, with diverse habitats and strong adaptability, with highly specialized important phenotypes such as missing limbs, body lengthening, visual and auditory deterioration, infrared induction enhancement, left and right lung asymmetric development and other special phenotypes, in the evolutionary history at the key node of vertebrate evolution, is an important group of vertebrates and an ideal group to study the formation mechanism of complex traits of animals.

Phylogenetic framework of snakes. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

In this study, based on multidisciplinary crossover methods such as comparative genome and gene editing, the research team found that three amino acid residues specifically missing the PTCH1 protein of snakes may be one of the important genetic mechanisms of limb deletion. In order to adapt to the body lengthening, the internal organs of snakes have undergone asymmetric development, such as most of their left lungs tend to degenerate, while the right lung is more developed. The loss of DNAH3 and FXJ11B genes that control the symmetrical development of organs in snakes is an important genetic factor in the asymmetric development of their left and right lungs.

In addition, this study also explored the evolutionary genetic mechanism of the special phenotype of infrared sensing snakes and cave-dwelling blind snake species, and found that the convergent evolution of noncoding regulatory elements of PMP22 gene related to thermal response and NFIB gene related to trigeminal neural development is an important genetic driving force for the perception infrared spectrum of some snakes. Blind snake species adapt to cave life through the loss of genes such as RPGRIP1 and the rapid evolution of genes such as CHIA, and form a feeding behavior that exclusively eats ants and ant eggs.

Evolutionary genetic mechanisms of traits specific to snakes. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

In the future, we will focus on the development of corn snakes as model animals

Li Jiatang said that this study took the lead in launching large-scale omics research on reptiles, which is of great significance for understanding the evolutionary history of vertebrates, and will promote the development of animal evolutionary biology and other related disciplines.

The research team conducts snake research in the wild. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

The latest results support the previous hypothesis that snakes evolved from lizards, which will deepen people's understanding of the origin of snakes and the formation mechanism of their complex traits, and further promote the research of crawling and even vertebrate evolution and developmental biology, and can also provide important enlightenment and scientific support for animal genetics and breeding and the prevention and treatment of human related diseases.

The research team conducts snake research in the wild. Photo courtesy of Chengdu Institute of Biology, Chinese Academy of Sciences

Looking ahead, Li Jiatang revealed that the research team will focus on developing corn snakes as model animals and carrying out evolutionary developmental biology research. At the same time, the mining and application of important genetic resources such as snake venom provides scientific support for the research and development of antivenom and snake venom-derived drugs. The research team will also promote the development from basic science to applied basic science to better serve the major strategic needs of the country. (End)