RT Journal Article
SR Electronic
T1 Functional Characterization of the Morpheus Gene Family
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 116087
DO 10.1101/116087
A1 Cemalettin Bekpen
A1 Carl Baker
A1 Michael D. Hebert
A1 H. Bahar Sahin
A1 Matthew E. Johnson
A1 Arzu Celik
A1 James C. Mullikin
A1 NISC Comparative Sequencing Program
A1 Evan E. Eichler
YR 2017
UL http://biorxiv.org/content/early/2017/03/12/116087.abstract
AB DATA ACCESS The cDNA sequences reported in this paper have been deposited in the GenBank database (accession numbers): KF175165-KF175225 and BACs accession numbers that are used in this study: AC148621, AC190226, AC097327, AC097332, AC190226, AC097333, AC145401, AC187943, AC166855, AC166597, AC167295, AC235773, AC202644, and AC234805.ABSTRACT The burst of segmental duplications during human and great ape evolution focuses on a set of “core” duplicons encoding great-ape-specific gene families. Characterization of these gene families is complicated by their high copy number, incomplete sequence, and polymorphic nature. We investigate the structure, transcriptional diversity, and protein localization of the nuclear pore complex-interacting protein (NPIP) or Morpheus gene family. The corresponding core, LCRA, encodes one of the most rapidly evolving genes in the human genome; LCRA has expanded to ~20 copies from a single ancestral locus in Old World monkey and is associated with most of the recurrent chromosome 16 microdeletions implicated in autism and mental retardation. Phylogenetic analysis and cDNA sequencing suggest two distinct subfamilies or subtypes, NPIPA and NPIPB. The latter expanded recently within the great apes due to a series of structural changes within the canonical gene structure. Among Old World monkey, we observe a testis-specific pattern of expression that contrasts with the ubiquitous pattern observed among human tissues. This change in the expression profile coincides with the structural events that reshaped the structure and organization of the gene family. Most of the expressed human copies are capable of producing an open reading frame. Immunofluorescence analyses of the morpheus genes showed a primary localization to both the nucleus and its periphery. We show that morpheus genes may be upregulated upon pI:C treatment and find evidence of human autoantibodies produced against the NPIPB protein, raising the possibility that morpheus genes may be related to immune- or autoimmune-related function.