Phylogenetic analysis showed that the tMRCA
of the 4 CCHFV variants diverged to produce 2 lineages, 1 containing variants A, B, and C and the other containing variant D.
(15) in the USA, where subtype 1b showed a TMRCA
of 1922 and an exponential increase.
Although the TMRCAs
of the mtDNA and Y chromosomes are around the same date as the earliest fossils with modern morphology, the much higher levels of retained diversity in the autosomal chromosomes are only compatible with an earlier bottleneck, not with two people.
Additionally, the Monte Carlo results showed that the historical gene flow between quetzal subspecies was interrupted at least three million years ago and TMRCA
estimated a gene interruption of three to six million years ago.
Several factors determine how TMRCA
of genes and the timing of speciation events coincide: (1) the effective size of the ancestral species; (2) the time since the species became isolated; (3) whether migration has or has not been occurring at some low rate; and (4) whether the genes examined are selectively neutral.
Single-Nucleotide Polymorphism Core Gene Alignment and tMRCA
The mean times to the most recent common ancestor (tMRCAs
) of the HA and NA genes for the 2015-2016 Pakistan strains were both estimated as late 2010 (Table 2), and sublineage B2 mean tMRCAs
were estimated as 2005-2006.
The estimated TMRCA
of lineage C is December 2013 (95% highest posterior density October 2013-January 2014).
The time to the most recent common ancestor (tMRCA
) estimated by pooling the information across all the gene segments in a hierarchical model (online Technical Appendix 1) suggested that a virus with this gene constellation emerged during October-December 2016 (Table 2; online Technical Appendix 1 Table 1).
These viruses were the closest relatives for 4 of the 8 North American segments that contributed to the H5Nx reassortants based on the time of most recent common ancestry (tMRCA
) analysis (online Technical Appendix Figures 2-12).
However, estimating the time to most recent common ancestor (TMRCA
) of the human cases will indicate how long the infection has been spreading.
The tree topology accords with previous findings (2,4, 5), and time to most recent common ancestor (TMRCA
) of the epidemic in the Americas is similar to that previously estimated (2) (American epidemic clade A; Figure).