Evolutionary forces in diabetes and hypertension pathogenesis in Africans

Area of Science:

• Genomics
• Evolutionary Biology
• Public Health

Background:

• Type 2 diabetes (T2D) and hypertension prevalence are rising in urbanizing sub-Saharan Africa (SSA).
• Lifestyle factors are primary drivers, but genetic variation shaped by natural selection also plays a role.
• Adaptive genomics studies in African populations remain scarce.

Purpose of the Study:

• To investigate the effects of natural selection on African genomes related to T2D and hypertension.
• To identify specific genes and biological mechanisms influenced by selection.
• To understand the adaptive significance of these genetic variations in the African context.

Main Methods:

• Analysis of African genomes for evidence of selection.
• Examination of genes involved in energy metabolism, adipose tissue biology, insulin action, and salt retention.
• Correlation of hypertension susceptibility variants with geographical latitude.

Main Results:

• Selection effects were observed in genes like PPARA and TCF7L2, potentially altering carbohydrate and lipid metabolism.
• African-ancestry-specific adipose tissue characteristics (low visceral adipose tissue, high intermuscular adipose tissue) may be adaptive.
• Selection impacts on insulin action (genes MPHOSPH9, TMEM127, ZRANB3, MC3R) suggest adaptation to famine and inflammation.
• Latitude correlation supports selection for salt retention mechanisms in warmer climates.

Conclusions:

• Natural selection has shaped African genomes, influencing mechanisms relevant to T2D and hypertension.
• These genetic adaptations may have provided historical advantages against environmental challenges.
• Further research is crucial, encompassing diverse African populations and functional assessments of risk loci.