Adaptive Gene Loss? Tracing Back the Pseudogenization of the Rabbit CCL8 Chemokine.
Studies of the process of pseudogenization have widened our understanding of adaptive evolutionary change. In Rabbit, an alteration at the second extra-cellular loop of the CCR5 chemokine receptor was found to be associated with the pseudogenization of one of its prime ligands, the chemokine CCL8. This relationship has raised questions about the existence of a causal link between both events, which would imply adaptive gene loss. This hypothesis is evaluated here by tracing back the history of the genetic modifications underlying the chemokine pseudogenization. The obtained data indicate that mutations at receptor and ligand genes occurred after the lineage split of New World Leporids versus Old World Leporids and prior to the generic split of the of Old World species studied, which occurred an estimated 8-9 million years ago. More important, they revealed the emergence, before this zoographical split, of a "slippery" nucleotide motif (CCCCGGG) at the 3' region of CCL8-exon2. Such motives are liable of generating +1G or -1G frameshifts, which could, however, be overcome by "translesion" synthesis or somatic reversion. The CCL8 pseudogenization in the Old World lineage was apparently initiated by three synapomorphic point mutations at the exon2-intron2 boundary which provide at short range premature terminating codons, independently of the reading frame imposed by the slippery motif. The presence of this motif in New World Leporids might allow verifying this scenario. The importance of CCL8-CCR5 signaling in parasite-host interaction would suggest that the CCL8 knock-out in Old World populations might be related to changes in pathogenic environment.
CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus Agrário de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal. cibio.up@cibio.up.pt.|Departamento de Zoologia e Antropologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal. cibio.up@cibio.up.pt.
Wessel
W
van der Loo
CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus Agrário de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal.
Maria João
MJ
Magalhaes
CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus Agrário de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal.|Departamento de Zoologia e Antropologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.|Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA.
Ana Lemos
AL
de Matos
CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus Agrário de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal.
Joana
J
Abrantes
Agriculture Forestry and Fisheries Research Council, Tsukuba, Japan.
Fumio
F
Yamada
CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus Agrário de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal.|Departamento de Zoologia e Antropologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.|Centro de Investigação em Tecnologias da Saúde, IPSN, CESPU, 4585-116, Gandra, Portugal.
Pedro J
PJ
Esteves
D000220:Adaptation, Biological / Q000235:genetics*; D000818:Animals; D054412:Chemokine CCL8 / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D009154:Mutation; D010802:Phylogeny; D011817:Rabbits; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
D054412:Chemokine CCL8; D019713:Receptors, CCR5
Adaptive gene loss; Chemokine; Co-evolution; Lagomorphs; Slipped frameshift reversion