The evolution of antimicrobial peptides in Chiroptera.

High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, ß-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three ß-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and ß-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.

Insights into mammalian TE diversity through the curation of 248 genome assemblies.

We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. We found that although mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree. Young TEs, particularly long interspersed elements, drive increases in genome size, whereas DNA transposons are associated with smaller genomes. Mammals tend to accumulate only a few types of TEs at any given time, with one TE type dominating. We also found association between dietary habit and the presence of DNA transposon invasions. These detailed annotations will serve as a benchmark for future comparative TE analyses among placental mammals.

Evolutionary constraint and innovation across hundreds of placental mammals.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Chiropterans Are a Hotspot for Horizontal Transfer of DNA Transposons in Mammalia.

Horizontal transfer of transposable elements (TEs) is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown to experience horizontal transfer of TEs at what appears to be a high rate compared with other mammals. We investigated the occurrence of horizontally transferred (HT) DNA transposons involving bats. We found over 200 putative HT elements within bats; 16 transposons were shared across distantly related mammalian clades, and 2 other elements were shared with a fish and two lizard species. Our results indicate that bats are a hotspot for horizontal transfer of DNA transposons. These events broadly coincide with the diversification of several bat clades, supporting the hypothesis that DNA transposon invasions have contributed to genetic diversification of bats.

A high-quality Ixodes scapularis genome advances tick science.

Ixodes spp. and related ticks transmit prevalent infections, although knowledge of their biology and development of anti-tick measures have been hindered by the lack of a high-quality genome. In the present study, we present the assembly of a 2.23-Gb Ixodes scapularis genome by sequencing two haplotypes within one individual, complemented by chromosome-level scaffolding and full-length RNA isoform sequencing, yielding a fully reannotated genome featuring thousands of new protein-coding genes and various RNA species. Analyses of the repetitive DNA identified transposable elements, whereas the examination of tick-associated bacterial sequences yielded an improved Rickettsia buchneri genome. We demonstrate how the Ixodes genome advances tick science by contributing to new annotations, gene models and epigenetic functions, expansion of gene families, development of in-depth proteome catalogs and deciphering of genetic variations in wild ticks. Overall, we report critical genetic resources and biological insights impacting our understanding of tick biology and future interventions against tick-transmitted infections.

Transposable Elements in Bats Show Differential Accumulation Patterns Determined by Class and Functionality.

Bat genomes are characterized by a diverse transposable element (TE) repertoire. In particular, the genomes of members of the family Vespertilionidae contain both active retrotransposons and active DNA transposons. Each TE type is characterized by a distinct pattern of accumulation over the past ~40 million years. Each also exhibits its own target site preferences (sometimes shared with other TEs) that impact where they are likely to insert when mobilizing. Therefore, bats provide a great resource for understanding the diversity of TE insertion patterns. To gain insight into how these diverse TEs impact genome structure, we performed comparative spatial analyses between different TE classes and genomic features, including genic regions and CpG islands. Our results showed a depletion of all TEs in the coding sequence and revealed patterns of species- and element-specific attraction in the transcript. Trends of attraction in the distance tests also suggested significant TE activity in regions adjacent to genes. In particular, the enrichment of small, non-autonomous TE insertions in introns and near coding regions supports the hypothesis that the genomic distribution of TEs is the product of a balance of the TE insertion preference in open chromatin regions and the purifying selection against TEs within genes.

SINE-Based Phylogenomics Reveal Extensive Introgression and Incomplete Lineage Sorting in Myotis.

Using presence/absence data from over 10,000 Ves SINE insertions, we reconstructed a phylogeny for 11 Myotis species. With nearly one-third of individual Ves gene trees discordant with the overall species tree, phylogenetic conflict appears to be rampant in this genus. From the observed conflict, we infer that ILS is likely a major contributor to the discordance. Much of the discordance can be attributed to the hypothesized split between the Old World and New World Myotis clades and with the first radiation of Myotis within the New World. Quartet asymmetry tests reveal signs of introgression between Old and New World taxa that may have persisted until approximately 8 MYA. Our introgression tests also revealed evidence of both historic and more recent, perhaps even contemporary, gene flow among Myotis species of the New World. Our findings suggest that hybridization likely played an important role in the evolutionary history of Myotis and may still be happening in areas of sympatry. Despite limitations arising from extreme discordance, our SINE-based phylogeny better resolved deeper relationships (particularly the positioning of M. brandtii) and was able to identify potential introgression pathways among the Myotis species sampled.