Physical mapping of EMR1 and CD97 in human Chromosome 19 and
assignment of Cd97 to mouse Chromosome 8 suggest an ancient
Ethan A. Carver,
Anne S. Olsen,
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, P.O. Box 808, L-452, Livermore, California 94550, USA
University of Tennessee–Oak Ridge School of Biomedical Sciences, Oak Ridge National Laboratory, 1060 Commerce Park, Oak Ridge, Tennessee
CLB and Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066 CX
Amsterdam, The Netherlands
Received: 10 March 1999 / Accepted: 8 June 1999
EMR1 and CD97 belong to the EGF-TM7 family of nonclassical
seven-span transmembrane receptors, members of which are ex-
pressed primarily in the immune system. The membrane-spanning
regions of CD97, EMR1, and other EGF-TM7 proteins show sig-
nificant homology to the secretin receptor superfamily. However,
unlike this group of peptide hormone receptors, EMR1 and CD97
have extended extracellular portions that possess several EGF do-
mains at the N-terminus (McKnight and Gordon 1998). The EGF
domain region can function as a ligand-binding site, as demon-
strated by the interaction of CD97 with CD55 (Hamann et al.
1996). EMR1 and CD97 show a high degree of structural similar-
ity despite the fact that they share only about 31% amino acid
sequence identity. The similarity between these two proteins sug-
gests that CD97 and EMR1 coding sequences arose through an-
cient duplication of a common ancestral gene. CD97 has been
assigned to human Chromosome (Chr) 19p13.12–p13.2 by fluo-
rescence in situ hybridization (FISH; Hamann et al. 1995), and
EMR1 has been mapped to Chr 19p13.3 through a combination of
FISH and somatic cell hybrid analysis (Baud et al. 1995). These
data indicate that the two related genes are linked but separated by
a significant distance in the human genome.
Emr1 has been mapped to distal mouse Chr 17 within a region
related to human 19p13.3, tightly linked to the gene encoding
transcription factor Rfx2 (Lin et al. 1997; McKnight et al. 1997).
Interestingly, RFX1, which encodes a transcription factor protein
related to RFX2 in both structure and immune-system function,
has been mapped to 19p13.1 (Doyle et al. 1996), suggesting that
human RFX1 and CD97 might also be close neighbors. RFX1 and
RFX2 encode site-specific DNA binding proteins that serve criti-
cal immune-system functions (Reith et al. 1994) and are also
thought to have arisen from a common ancestral gene sequence in
distant evolutionary time. These data suggested that the tight link-
age of RFX2 to EMR1, and RFX1 to CD97, respectively, might
reflect an ancient duplication encompassing the predecessors of
both sets of immunologically active genes.
To investigate this possibility, we set out to define physical
locations of CD97 and EMR1 genes in the human and to determine
the location of Cd97 in mice. We localized the mouse Cd97 gene
by following the segregation of variant M. musculus and M. spre-
tus alleles of the gene in an interspecific backcross (Doyle et al.
1996; Stubbs et al. 1996). The results confirmed the tight linkage
of Cd97 and Rfx1 in central mouse Chr 8 (Fig. 1). To define the
positions of human CD97 and EMR1, we hybridized probes rep-
resenting the two genes to a Chr 19 cosmid library (Olsen et al.
1994), and positive cosmids were ordered within the Chr 19 metric
physical map (Ashworth et al. 1995). The human CD97 probe
identified several overlapping cosmids located in 19p13.1 between
the RFX1 and NOTCH3, approximately 700 kb and 400 kb away
from those two genes, respectively (Fig. 2). The EMR1 probe
detected two cosmid clones, 31568 and 34349; positive hybridiza-
tion of both clones was confirmed by PCR with gene-specific
Correspondence to: L. Stubbs
Fig. 1. Segregation pattern of Cd97 and surrounding genes mapping to
mouse Chr 8. The mouse Cd97 gene was localized by hybridizing a 1636-
bp fragment of a Cd97 cDNA clone generated by PCR with primers
mCD97.1-ctgtccctgatggtgaaggag [nt 1104–1124 of the (+) strand] and
mCD97.8-cctgcctcgtgtaccaggcag [nt 2719–2739 of the (−) strand] de-
signed from published sequence (GenBank accession նY18365; Hamann
et al. submitted). We followed the segregation of variant restriction frag-
ments detected by this probe in 118 progeny of a Mus musculus × M.
spretus interspecific backcross as reported elsewhere [(C3Hf/R1-
/+ × Mus spretus) × C3Hf/R1; Doyle et al. 1996; Stubbs et al.
1990, 1996)]. Data were analyzed with the Map Manager data analysis
program (Manly 1993). The segregation patterns of Cd97 and flanking loci
are shown at the bottom of the figure. Probes and variant fragments used
to map the flanking genes have been reported elsewhere (Doyle et al.
1996). Each column represents a type of parental or recombinant chromo-
some. The number of backcross animals inheriting a particular type of
chromosome is listed at the bottom of each column. White boxes represent
the inheritance of a Mus spretus allele for a particular set of loci, while
black boxes denote the presence of C3Hf/R1 alleles for the same genes. A
partial Chr 8 linkage map showing the location of Cd97 appears above the
chromosome segregation figure. Recombination distances between loci are
shown to the left of the chromosome in centimorgans. The positions of the
human homologs of each locus are given at the right of the chromosome.
Mammalian Genome 10, 1039–1040 (1999).
© Springer-Verlag New York Inc. 1999