Structure, Sequence, Chromosomal Location, and Evolution of the Human Ferredoxin Gene Family

Abstract

Ferredoxin is an iron-sulfur protein that serves as an electron transport intermediate for mitochondrial cytochromes P450 involved in steroid, vitamin D, and bile acid metabolism. We cloned and characterized the human ferredoxin gene family, which includes two expressed genes and two pseudogenes. Sequence analysis of this gene family revealed that it encodes only one protein product. The expressed genes were assigned to chromosome 11 and pseudogenes to chromosomes 20 and 21 by identifying single-copy probes from each gene segment and hybridizing them to DNA from rodent-human hybrid cells. The pseudogenes lacked introns and contained numerous mutations, including insertion, deletion, and substitution which rendered them inactive. They were 96% and 85% homologous to the expressed gene, yet they were only 78% homologous with each other. The intronless nature, higher diversity among themselves, and distinct chromosomal location of the pseudogenes suggests that they arose by independent, retroposon-mediated events.

Literature and patent analysis of the cloning and identification of human functional genes in China

“…Chinese scientists started to report the cloning and identification of human functional genes in the 1990s ( Figure 2D). In 1990, a group led by Zhong BangZhu from the Institute of Biochemistry and Cell Biology, Academia Sinica, Taiwan, studied the structure, sequencing, chromosome localization and evolution of the FDX1 gene from the human ferredoxin gene family [7]. Their work was the first Chinese study to be recorded in the NCBI database.…”

“…Chinese scientists began to clone and identify human functional genes in the early 1990s [7,8], but progress was slow. In the mid-1990s, a Committee of Experts in Biology from the National High Technology Research and Development Program (863 Program) proposed the "two 1%" goal which involved the inclusion of China in the HGP by contributing 1% of the total sequencing work, and by cloning and identifying 1% of the total human functional genes.…”

Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.

“…There is only one human gene for adrenodoxin reductase, located on chromosome 17q24-q25 (17)(18)(19) that is expressed in all human tissues examined, (20) hence a disorder in this gene should have effects extending far beyond the steroidogenic tissues. Similarly, there are one (21) or two (22) nearly identical genes for adrenodoxin closely linked on chromosome 1 1q22 (19,22,23) that encode identical proteins (23); this mRNA is also found in all tissues examined (24). Thus, it has generally been agreed that congenital lipoid adrenal hyperplasia represents a genetic defect in the human P450scc gene (1,25).…”

cAMP post-transcriptionally diminishes the abundance of adrenodoxin reductase mRNA.

“…This mRNA is induced by tropic hormones acting by way of cAMP (9)(10)(11) by stimulating P450scc gene transcription (12). Three species of human adrenodoxin mRNAs that differ only in the lengths of their 3' untranslated regions (13) are encoded by two genes (14,15) on chromosome 11q22 (8,16) that are expressed in all tissues examined (13). Adrenodoxin mRNA also accumulates in response to tropic hormones acting by way of cAMP (13,17,18), apparently through a posttranscriptional mechanism (S.T.B.…”