What does the knowledge of Von Hippel-Lindau (VHL) disease and genetics reveal about related evolution concepts?
Tracking Evolution
Done by detection in people
Polymerase Chain Reaction tests
Comparative Genomic Hybridization tests
Nature of Evolution
Divergent Evolution
Requires loss of heterozygosity in chromosome 3p
Tumors developed from a germline mutation
Convergent Evolution
Different tumors becoming similar as evolution occurs
DNA Variance and Mutation
Impact
Not on number of evolving disabilities
Not on sequence of evolving disabilities
Propagation
Negative Phenotypic Manifestations
Benign and cancerous tumors
In women
Pregnancy complications
Stop reproduction
Associated with tumors in different organs
Evolution of Disease in Particular Organs
Cerebellar Hemangioblastomas
3.5-year median evolution time
Brainstem Hemangioblastomas
Progress after 7 years
Median evolution time of 1.5 years
Renal Cysts and Carcinomas
First progression after approximately 7 years
Following evolutions occur after about 1 to 2 years
May progress to clear cell renal cell carcinomas
Evolve further through additional genetic alterations
Leads to intra-tumour heterogeneity
Tumor Phylogeny
Early Truncal Events
Inactivation of the VHL gene
Mutation in chromosome 3
Some parallel evolution observed
Caused by a mutation in VHL (a tumor suppressor) gene
Leads to VHL protein abnormalities
Protein Evolution
pVHL19 is conserved more
pVHL30 is conserved less
Not Necessarily Harmful
Doesn't always stop reproduction
Would allow for mutation to be passed down
Adequate life expectancy for reproduction
Males
Average of 59.4 years
Females
Average of 48.4 years
Inheriting Germline Mutation
These might never manifest negative phenotypes
Second mutation required may not occur
Phenotypic manifestations may skip generations
Inheritance
Autosomal Dominant Inheritance Pattern
50% for a parent to pass it to their child