The sequence of the gorilla fetal globin genes: evidence for multiple gene conversions in human evolution

Two fetal globin genes (G gamma and A gamma) from one chromosome of alowland gorilla (Gorilla gorilla gorilla) have been sequenced and comparedto three human loci (a G gamma-gene and two A gamma-alleles). A comparisonof regions of local homology among these five sequences indicates that longafter the duplication that produced the two nonallelic gamma-globin loci ofcatarrhine primates, about 35 million years (Myr) ago, at least one geneconversion event occurred between these loci. This conversion occurred notlong before the ancestral divergence (about 6 Myr ago) of Homo and Gorilla.After this ancestral divergence, a minimum of three more gene conversionevents occurred in the human lineage. Each human A gamma-allele sharesspecific sequence features with the gorilla A gamma-gene; one suchdistinctive allelic feature involves the simple repeated sequence in IVS 2.This suggests that early in the human lineage the A gamma-genes may haveundergone a crossing-over event mediated by this simple repeated sequence.The DNA sequences from coding regions of both G gamma- and A gamma-loci, acomparison of 292 codons in the corresponding gorilla and human genes, showan unusually low evolutionary rate, with only two nonsilent differencesand, surprisingly, not even one silent substitution. The two nonsynonymoussubstitutions observed predict a glycine at codon 73 and an arginine atcodon 104 in the gorilla A gamma-sequence rather than aspartic acid andlysine, respectively, in human A gamma. Because only arginine has beenfound at position 104 in gamma-chains of Old World monkeys, it mayrepresent the ancestral residue lost in gorilla and human G gamma-chainsand in the human A gamma-chain. Possibly the arginine codon (AGG) wasreplaced by the lysine codon (AAG) in the G gamma-gene of a common ancestorof Homo and Gorilla and then was transferred to the A gamma-gene bysubsequent conversions in the human lineage. DNA sequence conversions,similar to that attributed to the fetal gamma-globin genes, appear to berelatively frequent phenomena and, if widespread throughout the genome, mayhave profound evolutionary consequences.