Genes and gene families - Human Gene Evolution - page 147

Kyrpides and Woese, 1998), between prokaryotic and eukaryotic RNA-binding
proteins (Mulligan et al ., 1994) and between prokaryotic and eukaryotic type II
DNA topoisomerases and DNA polymerases (Forterre et al ., 1994). A consider-
able degree of homology has also been noted between prokaryotic and eukaryotic
aminoacyl-tRNA synthetases (Francklyn et al . 1997; Nagel and Doolittle, 1991;
see Section 4.2.1, Genes encoding tRNAs and aminoacyl-tRNA synthetase ).
The eukaryotic cell cytoskeleton contains a number of proteins, the most abun-
dant being actins, tubulins, myosins and cytokeratins (Little and Seehaus, 1988).
The evolutionary origin of these proteins is intimately bound up with the origins
of the eukaryotic cell itself (Doolittle, 1992). Thus

-tubulin is thought to have

evolved before the -tubulins diverged from each other and since these

three tubulin isotypes are found in all eukaryotes, their origins must have pre-
ceded the eukaryotic divergence (Ludueña 1998). Consistent with this postulate,
sequence similarities exist between eukaryotic actins and tubulins and bacterial
ftsA and ftsZ proteins (Doolittle, 1995).
There are many instances of genes present in E. coli or yeast having multiple
homologues in the human genome indicating that the gene family in question must
have expanded during evolution. One example of this are the helicase genes of the
RecQ family of which there are five known in the human genome ( WRN , 8p; BLM ,
15; RECQL , 12p12; RECQLA , 8q24.3; RECQL5 , 17q25) (Kitao et al ., 1998).
As one travels further back in evolutionary time, the similarity between gene
sequences tends to decay to an extent that only specific portions may be recog-
nizably homologous. These ancient conserved regions (ACRs) represent those
regions of greatest structural or functional importance and often correspond to
specific domains. ACRs common to both prokaryotes and eukaryotes have been
noted in a diverse array of proteins, for example enolase, glyceraldehyde 3-phos-
phate dehydrogenase, cytochrome c oxidase subunit I, aminoacyl-transfer RNA
(II) synthetases, HSP70 and HSP90 (see section 4.2.3), phosphoglycerate kinase,
pyruvate dehydrogenase E1

- and

, pyruvate kinase, ribosomal proteins L3 and P0
and triosephosphate isomerase (Green et al ., 1993). Ceruloplasmin ( CP ; 3q23-
q25) and coagulation factors V ( F5 ; 1q23) and VIII ( F8C ; Xq28) manifest
homologies to the small blue proteins of bacteria which have a role in electron
transfer (Rydén and Hunt, 1993). A 60 amino acid domain found in cystathion-
ine- -synthase ( CBS ; 21q22.3) is also found in a bacterial ABC transporter pro-

tein and in a putative protein found in archaebacteria (Bateman, 1997).
Phylogenetic studies have suggested that the emergence of cytochrome oxidase
(a key enzyme in aerobic metabolism) (Castresana et al ., 1994), the aldehyde
dehydrogenases (e.g. ALDH1 , 9q21; ALDH3 , 17; ALDH5 , 9; ALDH6 , 15q26;
ALDH9 , 1; ALDH10 , 17p11.2; Yoshida et al ., 1998), carbamoyl phosphate syn-
thetase (a key enzyme of arginine and pyrimidine biosynthesis) ( CPS1 ; 2q35;
Schofield 1993; Lawson et al ., 1996), the protein synthesis elongation factors Tu
( TUFM ; 16p11) and G ( EEF1G ) (Baldauf et al ., 1996), tRNA splicing endonucle-
ase (Trotta et al ., 1997) and the glucose-6-phosphate isomerase gene family ( GPI ;
19q13; Hattori et al ., 1995) all predated the divergence of prokaryotes and eukary-
otes. The RadA protein that catalyzes DNA pairing and strand exchange is pre-
sent not only in all eukaryotes including human ( RECA ; 15q15.1) but also has
homologues in both prokaryotes (RecA) and the archaea (Seitz et al ., 1998).