The human growth hormone gene locus: structure, evolution, and allelic variations

Area of Science:

• Molecular Biology
• Human Genetics
• Genomics

Background:

• Human growth hormone (hGH) and chorionic somatomammotropin (hCS) are closely related genes with critical physiological roles.
• Understanding the genomic organization and evolutionary history of the hGH/hCS locus provides insights into gene regulation and function.

Purpose of the Study:

• To isolate and reconstruct the entire human GH/CS chromosomal locus.
• To characterize the nucleotide sequences of hCS genes and identify evolutionary mechanisms.
• To investigate the structural organization and evolutionary pathways of the hGH/hCS gene family.

Main Methods:

• Isolation of genomic clones containing hGH and hCS genes using lambda bacteriophage and cosmid libraries.
• Reconstruction of the GH/CS locus by analyzing overlapping restriction fragments.
• Determination of nucleotide sequences for hCS-5 and an allelic variant of hCS-2.
• Localization of repetitive sequences (Alu) and unique sequences within the locus.

Main Results:

• The hGH/hCS locus spans 48 kb and contains two GH genes and three CS genes in a specific order.
• The hCS-5 gene was identified as a pseudogene due to a splice site mutation.
• The hCS-2 gene variant showed a single amino acid substitution and codon deletion.
• At least 27 Alu repetitive sequences and three unique sequences were identified, suggesting evolutionary duplication breakpoints.
• Evidence for gene conversion between hCS-1 and hCS-2 gene precursors was found.

Conclusions:

• The hGH/hCS gene locus evolved primarily through gene duplication mechanisms.
• Concerted evolution, including gene conversion, has also shaped the hGH/hCS locus.
• Comparative analysis of hCS gene structures across mammalian species is warranted.