Genes and gene families - Human Gene Evolution - page 197

would imply the occurrence of adaptive amino acid replacements that have been
positively selected during evolution. Although sequence convergence has been
invoked in many different situations, there are still no convincing examples of
unrelated sequences which adhere to these criteria such that they warrant the use
of the term sequence convergence .
4.4 Coevolution
Coevolution can be said to be operating in cases where the process of evolutionary
change experienced at one locus is influenced by changes that have occurred at
another locus. At its simplest, coevolution can occur when two genes are inti-
mately associated as in the case of shared bidrectional promoter elements
(Chapter 5, section 5.1.5). More complex situations involve unlinked genes.
Fryxell (1996) proposed that 'the acquisition of a novel function by a duplicated
gene could be facilitated by pre-existing heterogeneity in proteins that interact
directly with the product of the duplicated gene'. Thus, the duplication and func-
tional divergence of one gene might serve to create an altered genetic environ-
ment that could promote the divergence of duplicate copies of genes encoding
proteins that interact with the protein products of the first gene.
In a study of the interspecies diversity manifested by a series of 48 ligand-recep-
tor pairs, Murphy (1993) demonstrated there to be a linear relationship between
receptor divergence and ligand divergence. Interestingly, the inter-species differ-
ences in receptor structure were nonrandomly distributed and largely confined to
the extracellular domains that interact with the ligand. Since this study employed
ligand-receptor pairs from diverse systems (host defence proteins, neurotransmit-
ters, hormones, growth factors and cell adhesion proteins), it is reasonable to sup-
pose that the coevolution of genes encoding interacting proteins is not an
uncommon phenomenon.
The coevolution of families of receptors and their ligands is perhaps best exem-
plified by the insulin-nerve growth factor family and their receptors (Section 4.2.3,
Insulin and insulin-like growth factor genes ; Fryxell, 1996). These ligand-receptor
pairs include insulin ( INS ; 11p15.5) and insulin receptor ( INSR ; 19p13), insulin-
like growth factor 1 ( IGF1 ; 12q22-q23) and its receptor ( IGF1R ; 15q25-qter),
brain-derived neurotrophic factor ( BDNF ; 11p13) and neurotrophin 5 ( NTF5 ;
19q13.3) and their cognate receptor neurotrophic tyrosine kinase receptor type 2
( NTRK2 ; 9q22.1), neurotrophin 3 ( NTF3 ; 12p13) and neurotrophic tyrosine
kinase receptor type 3 ( NTRK3 ; 15q25), nerve growth factor ( NGFB ; 1p13.1) and
neurotrophic tyrosine kinase receptor type 1 ( NTRK1 ; 1q21-q22). The ligand-
encoding genes share a common ancestry as do the genes encoding their receptors
(Fryxell, 1996). As new trophic factors emerged by duplication and divergence, so
their cognate receptors evolved by a similar parallel process. Other examples of the
coevolution of ligands and their receptors include interleukin 8 ( IL8 ; 4q13-21)
and its receptors ( IL8RA , IL8RB ; 2q35; Ahuja et al ., 1992), interleukin 4 ( IL4 ;
5q23-q31), and interleukin 4 receptor ( IL4R ; 16p11-p12; Richter et al ., 1995), the
gonadotropins and their receptors (Moyle et al ., 1994) and the nuclear receptors
and their ligands (Escriva et al ., 1997; section 4.2.3, Nuclear receptor genes ).