This invention provides human mtDNA polymorphisms that are diagnostic of all the major human haplogroups and methods of diagnosing those haplogroups and selected subhaplogroups. This invention also provides methods for identifying evolutionarily significant mitochondrial
DNA genes,
nucleotide alleles, and
amino acid alleles. Evolutionarily significant genes and alleles are identified using one or two populations of a
single species. The process of identifying evolutionarily significant
nucleotide alleles involves identifying evolutionarily significant genes and then evolutionarily significant
nucleotide alleles in those genes, and identifying evolutionarily significant
amino acid alleles involves identifying amino acids encoded by all nonsynonymous alleles. Synonymous codings of the nucleotide alleles encoding evolutionarily significant
amino acid alleles of this invention are equivalent to the evolutionarily significant amino acid alleles disclosed herein and are included within the scope of this invention. Synonymous codings include alleles at neighboring nucleotide loci that are within the same codon. This invention also provides methods for associating haplogroups and evolutionarily significant nucleotide and amino acid alleles with predispositions to physiological conditions. Methods for diagnosing predisposition to LHON, and methods for diagnosing increased likelihood of developing
blindness, centenaria, and increased
longevity that are not dependent on the geographical location of the individual being diagnosed are provided herein. Diagnosis of an individual with a predisposition to an
energy metabolism-related
physiological condition is dependent on the geographic region of the individual. Physiological conditions diagnosable by the methods of this invention include healthy conditions and
pathological conditions. Physiological conditions that are associated with haplogroups and with alleles provided by this invention include energetic imbalance,
metabolic disease, abnormal
energy metabolism, abnormal temperature regulation, abnormal
oxidative phosphorylation, abnormal
electron transport,
obesity, amount of body fat, diabetes, hypertension, and cardiovascular
disease.