Evolution trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper

31 Snake's numerous fascinating features distinctive from other tetrapods necessitate a rich 32 history of genome evolution that is still obscure. To address this, we report the first 33 high-quality genome of a viper, Deinagkistrodon acutus and comparative analyses using 34 other species from major snake and lizard lineages. We map the evolution trajectories of 35 transposable elements (TEs), developmental genes and sex chromosomes onto the snake 36 phylogeny. TEs exhibit dynamic lineage-specific expansion. And in the viper many TEs 37 may have been rewired into the regulatory network of brain genes, as shown by their 38 associated expression with nearby genes in the brain but not in other tissues. We detect 39 signatures of adaptive evolution in olfactory, venom and thermal-sensing genes, and also 40 functional degeneration of genes associated with vision and hearing. Many Hox and Tbx 41 limb-patterning genes show evidence of relaxed selective constraints, and such genes' 42 phylogenetic distribution supports fossil evidence for a successive loss of forelimbs then 43 hindlimbs during the snake evolution. Finally, we infer that the Z and W sex 44 chromosomes had undergone at least three recombination suppression events at the 45 ancestor of advanced snakes, with the W chromosomes showing a gradient of 46 degeneration from basal to advanced snakes. These results, together with all the genes 47 identified as undergoing adaptive or degenerative evolution episodes at respective snake 48 lineages forge a framework for our deep understanding into snakes' molecular evolution 49 history. 50 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. 3 Snakes have undergone massive adaptive radiation with ~3400 extant species 51 successfully inhabiting almost all continents except for the polar regions 1. This process 52 has culminated in 'advanced snakes' (Caenophidia, ~3000 species), involved numerous 53 evolutionary changes in body form, chemo-/thermo-perception, venom and sexual 54 reproductive systems, which together distinguish snakes from majorities of other 55 Squamates (lizards and worm lizards). Some of these dramatic changes can be tracked 56 from fossils, which established that the ancestor of snakes had already evolved a 57 elongated body plan, probably as an adaptation to a burrowing and crawling lifestyle, but 58 had lost only the forelimbs 2-4. Extant boa and python species retain rudimentary 59 hindlimbs, while advanced snakes have completely lost them. The limblessness, 60 accompanied by degeneration in visual and auditory perception have not compromised 61 snakes' dominant role as …