A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients.
In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches.
Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.
Joshua B
JB
Benoit
Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.
Geoffrey M
GM
Attardo
Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America; Section of Molecular and Applied Zoology, Institute of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia.
Veronika
V
Michalkova
Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.
Tyler B
TB
Krause
Section of Molecular and Applied Zoology, Institute of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia.
Jana
J
Bohova
Departments of Entomology and Evolution, Ecology and Organismal Biology, The Ohio State University, Columbus, Ohio, United States of America.
Qirui
Q
Zhang
Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America.
Aaron A
AA
Baumann
Department of Biochemistry and Molecular Biology, Egerton University, Njoro, Kenya.
Paul O
PO
Mireji
Section of Molecular and Applied Zoology, Institute of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia.
Peter
P
Takáč
Departments of Entomology and Evolution, Ecology and Organismal Biology, The Ohio State University, Columbus, Ohio, United States of America.
David L
DL
Denlinger
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
Jose M
JM
Ribeiro
Division of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.
Serap
S
Aksoy
D000019:Abortifacient Agents / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons / Q000187:drug effects / Q000235:genetics; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D055785:Gene Knockdown Techniques / Q000379:methods; D017344:Genes, Insect / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics*; D007438:Introns / Q000187:drug effects / Q000235:genetics; D007774:Lactation / Q000187:drug effects / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D008894:Milk Proteins / Q000235:genetics; D010802:Phylogeny; D020543:Proteome / Q000235:genetics; D012313:RNA / Q000235:genetics; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome / Q000235:genetics; D014370:Tsetse Flies / Q000187:drug effects* / Q000235:genetics*
D000019:Abortifacient Agents; D019476:Insect Proteins; D008894:Milk Proteins; D020543:Proteome; D012313:RNA