Secondly, if two phenotypes contribute to complexity, they must be genetically separable: some mutations must exist that affect one phenotype but not the other.
This further underscores the fact that other still unknown mutations must exist in addition to yet unreported phenotypic variants associated with known or unknown disease-associated genes.
Since this phenomenon was detected by the GP method that cannot detect the mutation of less than 10-5/base/replication, a large number of accumulated mutations must exist between distantly located cells in the tree.
For diversity to evolve, variation must exist in a population, and the source of this variation will be determined by genetic factors, including point mutations and genomic rearrangements.
Once genetic variation is created through new mutations, mechanisms must exist to maintain the variation within populations, in order for the populations to readily evolve.
The mutation must be functionally relevant.
Thus, illustrative of many cancer syndromes and relevant to clinical practice, other predisposition genes must exist for PTEN mutation-negative CS/CSL individuals and families.
Since the cause is existent, the effect also must exist.
While this might represent the most efficient path to autoactivation, other, possibly less efficient paths must exist, that similarly rely on F595, since other JAK2 V617 mutations are also constitutively active (i.e. V617M, V617L, V617I [26]), and since the F595A mutation inhibits their activation (data not shown).
We now realize that the strict Lamarckian scenario is extremely demanding in that a molecular mechanism must exist for the effect of a phenotypic change to be channeled into the corresponding modification of the genome (mutation).
