An African American Paternal Lineage Adds an Extremely Ancient Root to theHuman Y Chromosome Phylogenetic Tree
Fernando L. Mendez,
Krishna R. Veeramah,
August E. Woerner,
Forka Leypey Mathew Fomine,
Mark G. Thomas,
Tatiana M. Karafet,
and Michael F. Hammer
WereportthediscoveryofanAfricanAmericanYchromosomethatcarriestheancestralstateofallSNPsthatdeﬁnedthebasalportionof the Y chromosome phylogenetic tree. We sequenced~240 kb of thischromosome to identify private, derivedmutationsonthislineage,which we named A00. We then estimated the time to the most recent common ancestor (TMRCA) for the Y tree as 338 thousand yearsago(kya)(95%conﬁdenceinterval
237–581kya).Remarkably,thisexceedscurrentestimatesofthemtDNATMRCA,aswellasthoseof theageoftheoldestanatomicallymodernhumanfossils.Theextremely ancientagecombinedwiththerarityoftheA00lineage,whichwe also ﬁnd at very low frequency in central Africa, point to the importance of considering more complex models for the origin of Y chromosome diversity. These models include ancient population structure and the possibility of archaic introgression of Y chromo-somesintoanatomicallymodernhumans.TheA00lineagewasdiscoveredinalargedatabaseofconsumersamplesofAfricanAmericansand has not been identiﬁed in traditional hunter-gatherer populations from sub-Saharan Africa. This underscores how the stochasticnature of the genealogical process can affect inference from a single locus and warrants caution during the interpretation of thegeographic location of divergent branches of the Y chromosome phylogenetic tree for the elucidation of human origins.
Characterizing the root of the phylogenetic tree of indi-vidual genetic loci has inﬂuenced many researchers intheir attempts to infer the time and place of the origin of anatomically modern humans (AMHs).
Analyses of thenonrecombining portion of the Y chromosome andmtDNA have suggested that recent common ancestorslived in sub-Saharan Africa within the last 200,000years.
However, estimates of the time to the most recentcommon ancestor (TMRCA) have been consistently lowerfor the Y chromosome (~60–140 thousand years ago[kya])
than for mtDNA (~140–240 kya).
A variety of evolutionary processes (e.g., natural selection, differentialmigration of males and females, and/or a skew in thebreeding sex ratio) have been invoked to explain thisdifference.
Genotyping of a DNA sample that was submitted toa commercial genetic-testing facility demonstrated thatthe Y chromosome of this African American individualcarried the ancestral state of all known Y chromosomeSNPs. To further characterize this lineage, which wedubbed A00 (seeFigure S1, available online, for proposednomenclature), we sequenced multiple regions (totaling
240 kb) of the X-degenerate portion of this chromosome,as well as a subset of these regions (~180 kb) on a chromo-somebelongingtothepreviouslyknownbasallineageA1b(which we rename here as A0). We note that all samplingprocedures described herein were approved by and per-formedaccordingtotheethicalstandardsoftheUniversityofArizonaHumanSubjectsCommittee.Theancestralstateof each polymorphic site was inferred with pairwise align-ments between the human (UCSC Genome Browser hg18)and chimpanzee (panTro3) reference sequences, andmutations were assigned to the branches (i.e., A00 andA0) shown as thick lines inFigure 1on the basis of an in-ﬁnite-sites model (Table S1). To estimate the TMRCA of theYchromosometreethatincorporatesthenewlydiscov-ered root deﬁned by A00, we developed a likelihood-basedmethod that uses mutation rates recently estimated byKong et al.,
who performed high-coverage whole-genome sequencing on 78 human pedigrees.Assuming that mutations in the X-degenerate portion of the Y chromosome follow the linear model presented byKong et al.,
we adjusted for male-speciﬁc mutationprocesses. If
is the mutation rate per year per basefor the Y chromosome,
is the length of sequenceanalyzed for the autosomes,
is the average number of new mutations per genome in the autosomes,
is thegeneration time,
is the increment in mutation rate perbase per year increment in the paternal age,
isthe number of mutations originating in the mother, and
is the average age of fathers in the study,
. We obtained medianvalues and generated 90% conﬁdence intervals (CIs) for
as a function of
(ranging from 20 to 40 years) bysampling 100,000 times from normal distributions foreach of the parameters
3.12]), whichresult from the number of observed mutations (4,933 in
Division of Biotechnology, Arizona Research Laboratories, University of Arizona, Tucson, AZ 85721, USA;
Genomic Research Center, Family Tree DNA,Houston, TX 77008, USA;
History Department, University of Yaounde´I, BP 337, Yaounde´, Cameroon;
Henry Stewart Group, London WC1A 2HN, UK;
2013 by The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics
, 454–459, March 7, 2013