Human fetal g γ- and A γ-globin genes: Complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes

Abstract We present the nucleotide sequences of the G γ - and A γ -globin genes from one chromosome (A) and of most of the A γ gene from the other chromosome (B) of the same individual. All three genes have a small, highly conserved intervening sequence (IVS1) of 122 bp located between codons 30 and 31 and a large intervening sequence (IVS2) of variable length (866–904 bp) between codons 104 and 105. A stretch of simple sequence DNA occurs in IVS2 which appears to be a hot spot for recombination. On the 5′ side of this simple sequence, the allelic A γ genes differ considerably in IVS2 whereas the nonallelic G γ - and A γ genes from chromosome A differ only slightly. Yet on the 3′ side of the simple sequence, the allelic genes differ only slightly whereas the nonallelic genes differ considerably. We hypothesize that the 5′ two thirds of the A γ gene on chromosome A has been "converted" by an intergenic exchange to become more like the G γ gene on its own chromosome A than it is like the allelic A γ gene on the other chromosome B. Our sequence data suggest that intergenic conversions occur in the germ line. The DNA sequence differences between two chromosomes from a single individual strongly suggest that DNA sequence polymorphisms for localized deletions, additions and base substitutions are very common in human populations.

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