We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.

24As coral populations decline worldwide in the face of ongoing environmental change, 25 documenting their distribution, diversity and conservation status is now more imperative than 26 ever. Accurate delimitation and identification of species is a critical first step. This task, 27 however, is not trivial as morphological variation and slowly evolving molecular markers 28 confound species identification. New approaches to species delimitation in corals are needed to 29 overcome these challenges. Here, we test whether target enrichment of ultraconserved elements 30 (UCEs) and exons can be used for delimiting species boundaries and population structure within 31 species of corals by focusing on two octocoral genera, Alcyonium and Sinularia, as exemplary 32 case studies. We designed an updated bait set (29,363 baits) to target-capture 3,040 UCE and 33 exon loci, recovering a mean of 1,910 ± 168 SD per sample with a mean length of 1,055 ± 208 34 bp. Similar numbers of loci were recovered from Sinularia (1,946 ± 227 SD) and Alcyonium 35(1,863 ± 177 SD). Species-level phylogenies were highly supported for both genera. Clustering 36 methods based on filtered SNPs delimited species and populations that are congruent with 37 previous allozyme, DNA barcoding, reproductive and ecological data for Alcyonium, and offered 38 further evidence of hybridization among species. For Sinularia, results were congruent with 39 those obtained from a previous study using Restriction Site Associated DNA Sequencing. Both 40 case studies demonstrate the utility of target-enrichment of UCEs and exons to address a wide 41 range of evolutionary and taxonomic questions across deep to shallow time scales in corals. 42 43