Professional Documents
Culture Documents
net/publication/320827727
CITATIONS READS
24 1,559
5 authors, including:
Some of the authors of this publication are also working on these related projects:
Search for soot and/or nanodiamonds associated with impacts or extinctions View project
All content following this page was uploaded by Todd J. Braje on 03 November 2017.
F
curs during disease progression. Clearly, (1999).
this discovery will provide new tools to 9. R. Rizzuto et al., Science 280, 1763 (1998). or much of the 20th century, most
10. M. J. Berridge, M. D. Bootman, H. L. Roderick, Nat. Rev. Mol.
better understand the ER-mitochondrial Cell Biol. 4, 517 (2003).
archaeologists believed humans first
axis with respect to physiology and disease 11. S.-K. Kwon et al., PLOS Biol. 14, e1002516 (2016). colonized the Americas ~13,500 years
across cell types. 12. R. Heidelberger, C. Heinemann, E. Neher, G. Matthews, ago via an overland route that crossed
Nature 371, 513 (1994).
Although several mammalian ER-mi- Beringia and followed a long and
13. A. Tran-Van-Minh, T. Abrahamsson, L. Cathala, D. A.
tochondrial tethering proteins have been DiGregorio, Neuron 91, 837 (2016). narrow, mostly ice-free corridor to
proposed, most lack clear indisputable evi- 14. D. Tsay, J. T. Dudman, S. A. Siegelbaum, Neuron 56, 1076 the vast plains of central North America.
dence, and the identification of bona fide (2007). There, Clovis people and their descendants
15. S. Paillusson et al., Trends Neurosci. 39, 146 (2016).
ER-mitochondrial tethers has remained hunted large game and spread rapidly
elusive. We now have the first description through the New World. Twentieth-century
of a protein that appears to primarily func- 10.1126/science.aaq0141 discoveries of distinctive Clovis artifacts
throughout North America, some associ-
ated with mammoth or mastodon kill sites,
supported this “Clovis-first” model. North
Coupling ER and mitochondrial membranes America’s coastlines and their rich marine,
The proteins that mediate the close coupling of ER and mitochondrial membranes (tethering) in mammalian
estuarine, riverine, and terrestrial ecosys-
cells have remained elusive. PDZD8 is an ER-bound protein that is critical for the tight association of ER and
tems were peripheral to the story of how
mitochondrial membranes. This will now allow the search for other possible binding partners and regulators
that make-up this newly identified tethering complex in mammalian cells.
and when the Americas were first settled
by humans. Recent work along the Pacific
coastlines of North and South America
has revealed that these environments were
Ca2+ Ca2+ ER-mitochondria tethering settled early and continuously provided a
rich diversity of subsistence options and
Calcium transport technological resources for New World
ER
RYR IP3R hunter-gatherers.
Subcellular signaling domains Confidence in the Clovis-first theory
PDZD8 started to crumble in the late 1980s and
1990s, when archaeological evidence for
SMP domain Ca2+ Ca2+ Lipid/membrane homeostasis late Pleistocene seafaring and maritime
Ca 2+
colonization of multiple islands off east-
? ern Asia (such as the Ryukyu Islands and
? Neurotransmitter release
Ca2+ the Bismarck Archipelago) accumulated.
By the early 2000s, the Clovis-first theory
Ca2+
Cell death collapsed after widespread scholarly accep-
Mitochondria
GRAPHIC: V. ALTOUNIAN/SCIENCE
ers (9, 10). Kelp resources extended as far shore (and at greater depth) the evidence Answers to the questions of how, when,
south as Baja California, and then—after a may lie, enlarging already vast potential and where humans first reached the Ameri-
gap in Central America, where productive search areas on the submerged continen- cas remain tentative. The small sample of
mangrove and other aquatic habitats were tal shelf. But although direct evidence of pre-Clovis sites has yet to produce a coher-
available—picked up again in northern a maritime pre-Clovis dispersal has yet to ent technological signature with the broad
Peru, where the cold, nutrient-rich waters emerge, recent discoveries confirm that geographic patterning that characterizes
from the Humboldt Current supported kelp late Pleistocene archaeological sites can be Clovis. Distinctive fluted Clovis, other
forests as far south as Tierra del Fuego. found underwater. Recent discoveries at the fluted paleoindian, and fishtail points
T
northeast Asian origin for Native Ameri- both copy number and sequence (5). This
can ancestors some time in the past 20,000 he vast majority of eukaryotes have has led to two very different ideas. There
years. But more data are needed to close two copies of each chromosome and could be something about extremely repeti-
substantial spatial and temporal gaps be- reproduce sexually. Meiosis is a vital tive short DNA sequences that is essential
tween these far-flung finds and trace a process that produces gametes (eggs for function, or these short DNA sequences
dispersal route from Asia to the Americas. and sperm) by reducing the number might be selfish and promote their own in-
Work on early coastal localities along the of chromosome copies to one; fertil- heritance without any functional benefit for
Pacific Coast from Alaska to Baja California ization between egg and sperm restores the the host organism (2). This is remarkable
(8), Peru (10), and Chile (1) is helping to fill chromosome copy number to two. During because centromeric repeats are the most
these gaps. female meiosis, one set of chromosomes is abundant class of noncoding DNA in our
If the first Americans followed a coastal expelled into a tiny cell called a polar body, genome, and we do not know what they are
route from Asia to the Americas, finding whereas the other is segregated into the egg. for, if anything. Recent work has lent strong
evidence for their earliest settlements will It is a fundamental tenet of genetics that support to the idea of centromeres as selfish
require careful consideration of the effects there is a random, 50% chance for any par- fragments of DNA.
of sea level rise and coastal landscape evo- ticular chromosome to be segregated into the Standard laboratory mouse strains have
lution on local and regional archaeological egg versus the polar body. However, cases in 20 different chromosomes, each with its
records (15). Around the globe, evidence for which one copy of a chromosome is inherited centromere at one end (telocentric). In con-
coastal occupations between ~50,000 and with greater than 50% frequency have been trast, certain isolated populations of wild
15,000 years ago are rare because of post- reported in many species (1), but the molecu- mice have 10 chromosomes, each formed by
glacial sea level rise, marine erosion, and fusion of two telocentric chromosomes into
shorelines that have migrated tens or even one chromosome, with its centromere in the
hundreds of kilometers from their locations middle (metacentric). The female offspring
at the LGM. Overcoming these obstacles re- Pullquote or liftout quote of a cross between a telocentric strain and a
quires interdisciplinary research focused piece tops on baseline metacentric strain exhibit a property called
on coastal areas with relatively steep off- meiotic drive. Instead of transmitting a
shore bathymetry, formerly glaciated areas as shown a “synthesis of pair of telocentric chromosomes to 50% of
where ancient shorelines have not shifted
so dramatically, or the submerged land-
dummy type goes here.” their offspring and the homologous meta-
centric chromosome to 50% of their off-
scapes that are one of the last frontiers for spring, they preferentially transmit either
archaeology in the Americas. Methodologi- lar mechanism of this preferential inheri- telocentric or metacenric chromosomes (6).
cal and analytical advances are moving tance has remained obscure. Recent work These findings have remained somewhat
us closer than ever toward understanding has indicated that centromeres, the chro- obscure because the phenomenon only ex-
when, how, and why people first colonized mosomal regions that form attachments to plains why wild populations of mice tend
the Americas. Coastal regions are central to microtubules that mediate chromosome seg- to have all metacentric or all telocentric
this debate. j regation during meiosis, compete with each chromosomes, and the mechanism has been
other for inheritance during female meiosis largely unknown. Recent work has shown
REF ERENC ES AND NOTES
(2). Thus, the essential DNA sequences that that chromosomes that are preferentially
1. T. D. Dillehay et al., PLOS One 10, e0141923 (2015).
2. M. W. Pedersen et al., Nature 537, 45 (2016). mediate accurate chromosome segregation transmitted to offspring have up to sixfold
3. J. J. Halligan et al., Sci. Adv. 2, e1600375 (2016). are actually “selfish” (or parasitic) genetic more copies of the centromeric repeat se-
4. D. L. Jenkins et al., Science 337, 223 (2012). elements that have invaded our genome. On quence (7) and load more kinetochore pro-
5. M. R. Waters et al, Science 331, 1599 (2011).
6. M. R. Waters et al., Science 334, 351 (2011). page XXX of this issue, Akera et al. (3) pro- teins (6, 7) than do chromosomes that are
7. L. Bourgeon, A. Burke, T. Higham, PLOS One 12, e0169486 vide the most detailed molecular mechanism less frequently inherited. The preferentially
(2017). to date that explains how a parasitic DNA inherited centromeres with more copies of
8. L. Wade, Science 357, 542 (2017).
9. J. M. Erlandson et al., J. Isl. Coast. Arch. 2, 161 (2007).
sequence has used the asymmetry of oocyte centromeric repeats and more kinetochore
10. T. D. Dillehay et al., Sci. Adv. 3, e1602778 (2017). meiosis to ensure its own inheritance and proteins have been called “strong” centro-
11. B. Llamas et al., Sci. Adv. 2, e1501385 (2016). therefore its spread through populations. meres and are preferentially oriented to-
12. S. R. Holen et al., Nature 544, 479 (2017).
13 T. J.Braje et al., PaleoAmerica 3, 200 (2017).
Centromeric DNA is composed of more ward the egg side of the meiotic spindle.
14. J. M. Erlandson, T. J. Braje, Quatern. Int. 239, 28 (2011). than 1000 copies of a very short (100 to 300 “Weak” centromeres, with fewer copies of
15. D. W. Fedje, H. Josenhans, Geology 28, 99 (2000). centromeric repeats, are preferentially ori-
Department of Molecular and Cellular Biology, University of ented toward the plasma membrane, where
10.1126/science.aao5473 California, Davis, Davis, CA, USA. Email: fjmcnally@ucdavis.edu they will be deposited in a polar body after