NDLI: Evolutionary study of leporid CD4 reveals a hotspot of genetic variability within the D2 domain

Content Provider	Springer Nature Link
Author	Sousa Pereira, Patricia Abrantes, Joana Baldauf, Hanna Mari Keppler, Oliver T. Esteves, Pedro J.
Copyright Year	2016
Abstract	CD4 is the major receptor on T helper cells involved in the uptake of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) into their host cells. Evolutionary studies of CD4 in primates revealed signatures of positive selection in the D1 domain that interacts with primate exogenous lentivirus gp120 proteins. Here, we studied the evolution of CD4 in lagomorphs by comparing sequences obtained for the genera Oryctolagus, Sylvilagus, Lepus, and Ochotona. Our results reveal an overall higher divergence in lagomorphs compared to primates with highest divergence in the D2 domain. A detailed analysis of a small fragment of 33 nucleotides coding for amino acids 169 to 179 in the D2 domain showed dramatic amino acid alterations with a dN/dS value of 3.2 for lagomorphs, suggesting that CD4 is under strong positive selection in this particular region. Within each leporid genus, no significant amino acid changes were observed for the D2 domain which indicates that the genetic differentiation occurred in the ancestor of each genus before the species radiation. The rabbit endogenous lentivirus type K (RELIK) found in leporids shares high structural similarity with HIV which suggests a possible interaction between RELIK and CD4. The presence of RELIK in the studied leporids, the high structural similarity to modern-day exogenous lentiviruses and the absence of exogenous lentiviruses in leporids, allows us to hypothesize that this endogenous retrovirus, that was most probably exogenous in the past, drove the divergent evolution of leporid CD4.
Starting Page	477
Ending Page	482
Page Count	6
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	68
Issue Number	6-7
e-ISSN	14321211
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-03-15
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	CD4 Leporids Positive selection RELIK Immunology Human Genetics Gene Function Cell Biology Allergology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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