Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments

Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below -70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski's horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.

TRANSCRIPTIONAL AND POST-TRANSLATIONAL MECHANISMS CONTRIBUTE TO MAINTENANCE OF REST IN NEURAL TUMORS

The RE-1 silencing transcription factor (REST) is an important regulator of normal nervous system development. It negatively regulates neuronal lineage specification in neural progenitors by binding to its consensus RE-1 element(s) located in the regulatory region of its target neuronal differentiation genes. The developmentally coordinated down-regulation of REST mRNA and protein in neural progenitors triggers terminal neurogenesis. REST is overexpressed in pediatric neural tumors such as medulloblastoma and neuroblastoma and is associated with poor neuronal differentiation. High REST protein correlate with poor prognosis for patients with medulloblastoma, however similar studies have not been done with neuroblastoma patients. Mechanism(s) underlying elevated REST levels medulloblastoma and neuroblastoma are unclear, and is the focus of this thesis project. We discovered that transcriptional and post-translational mechanisms govern REST mis-regulation in medulloblastoma and neuroblastoma. In medulloblastoma, REST transcript is aberrantly elevated in a subset of patient samples. Using loss of function and gain of function experiments, we provide evidence that the Hairy Enhancer of Split (HES1) protein represses REST transcription in medulloblastoma cell lines, modulates the expression of neuronal differentiation genes, and alters the survival potential of these cells in vitro. We also show that REST directly represses its own expression in an auto-regulatory feedback loop. Interestingly, our studies identified a novel interaction between REST and HES1. We also observed their co-occupancy at the RE-1 sites, thereby suggesting potential for co-regulation of REST expression. Our pharmacological studies in neuroblastoma using retinoic acid revealed that REST levels are controlled by transcriptional and post-transcriptional mechanisms. Post-transcriptional mechanisms are mediated by modulation of E3 ligase or REST, SCFβ-TRCP, and contribute to resistance of some cells to retinoic acid treatment.

Geochemistry on smectites in sediment cores CRP-1 and CRP-2 from the Ross Sea, Antarctica

TEM (transmission electron microscopy) observations and microanalyses on smectite microparticles in the sediments of the CRP-2A core were carried out to determine their origin (authigenic or detrital) and the source rocks. Smectites are dioctahedral and are Fe-rich members of the nontronite-beidellite series. They generally display both flaky and hairy shapes, but no large compositional difference between the two forms was observed. Flaky smectites are detrital while hairy smectites probably formed in situ through the reorganisation of previous flaky particles. The source rocks for smectites are probably represented by the McMurdo Volcanic Group to the south, but also by the Ferrar Dolerites and Kirkpatrick Basalts in the Transantarctic Mountains. CRP-2A smectites are Fe and Mg richer than those of the coeval or not coeval levels of the CIROS-I, DSDP 270 and 274 cores. The average compositions of smectite in CRP-1 and CRP-2A cores show a downcore trend toward more alluminiferous terms, which might reflect the increase of the chemical weathering processes on the continent.

AMS radiocarbon dates and pollen analysis of ODP Hole 175-1078C

ODP Site 1078 situated under the coast of Angola provides the first record of the vegetation history for Angola. The upper 11 m of the core covers the past 30 thousand years, which has been analysed palynologically in decadal to centennial resolution. Alkenone sea surface temperature estimates were analysed in centennial resolution. We studied sea surface temperatures and vegetation development during full glacial, deglacial, and interglacial conditions. During the glacial the vegetation in Angola was very open consisting of grass and heath lands, deserts and semi-deserts, which suggests a cool and dry climate. A change to warmer and more humid conditions is indicated by forest expansion starting in step with the earliest temperature rise in Antarctica, 22 thousand years ago. We infer that around the period of Heinrich Event 1, a northward excursion of the Angola Benguela Front and the Congo Air Boundary resulted in cool sea surface temperatures but rain forest remained present in the northern lowlands of Angola. Rain forest and dry forest area increase 15 thousand years ago. During the Holocene, dry forests and Miombo woodlands expanded. Also in Angola globally recognised climate changes at 8 thousand and 4 thousand years ago had an impact on the vegetation. During the past 2 thousand years, savannah vegetation became dominant.

Distribution of pollen and spores in sediments of ODP Hole 175-1078C

The distribution of pollen in marine sediments is used to record vegetation change on the continent. Generally, a good latitudinal correspondence exists between the distribution patterns of pollen in the marine surface sediments and the occurrence of the source plants on the adjacent continent. To investigate land-sea interactions during deglaciation, we compare proxies for continental (pollen assemblages) and marine conditions (alkenone-derived sea surface temperatures) of two high-resolution, radiocarbon-dated sedimentary records from the tropical southeast Atlantic. The southern site is located West of the Cunene River mouth; the northern site is located West of the Angolan Huambe Mountains. It is inferred that the vegetation in Angola developed from Afroalpine and open savannah during the last Glacial maximum (LGM) via Afromontane Podocarpus forest during Heinrich Event 1 (H1), to an early increase of lowland forest after 14.5 ka. The vegetation record indicates dry and cold conditions during the LGM, cool and wet conditions during H1 and a gradual rise in temperature starting well before the Younger Dryas (YD) period. Terrestrial and oceanic climate developments seem largely running parallel, in contrast to the situation ca. 5° further South, where marine and terrestrial developments diverge during the YD. The cool and wet conditions in tropical West Africa, South of the equator, during H1 suggest that low-latitude insolation variation is more important than the slowdown of the thermohaline circulation for the climate in tropical Africa.

Mineralogy micromorphology, and geochemistry at DSDP Site 89-585

At Site 585 of Deep Sea Drilling Project Leg 89 more than 500 m of volcaniclastic to argillaceous middle-Late Cretaceous sediments were recovered. Analyses by X-ray diffraction (bulk sediment and clay fraction), transmission electron microscopy, molecular and atomic absorption, and electron microprobe were done on Site 585 samples. We identify four successive stages and interpret them as the expression of environments evolving under successive influences: Stage 1, late Aptian to early Albian - subaerial and proximal volcanism, chiefly expressed by the presence of augite, analcite, olivine, celadonite, small and well-shaped transparent trioctahedral saponite, Al hydroxides, Na, Fe, Mg, and various trace elements (Mn, Ni, Cr, Co, Pb, V, Zn, Ti). Stage 2, early to middle Albian - submarine and less proximal volcanic influence, characterized by dioctahedral and hairy Mg-beidellites, a paucity of analcite and pyroxenes, the presence of Mg and K, and local alteration of Mg-smectites to Mg-chlorites. Stage 3, middle Albian to middle Campanian - early marine diagenesis, marked by the development of recrystallization from fleecy smectites to lathed ones (all of alkaline Si-rich Fe-beidellite types), by the development of opal CT and clinoptilolite, and by proximal to distal volcanic influences (Na parallel to Ti, K). Local events consist of the supply of reworked palygorskite during the Albian-Cenomanian, and the recurrence of proximal volcanic activity during the early Campanian. Stage 4, late Campanian to Maestrichtian - development of terrigenous supply resulting from the submersion of topographic barriers; this terrigenous supply is associated with minor diagenetic effects and is marked by a clay diversification (beidellite, illite, kaolinite, palygorskite), the rareness of clay recrystallizations, and the disappearance of volcanic markers.

Pollen analysis of sediment cores from the mouth of the river Congo to Walvis Bay and Lüderitz

The distribution of pollen in marine sediments is used to record vegetation changes over the past 30,000 years on the adjacent continent. A transect of marine pollen sequences from the mouth of the river Congo (~5°S) to Walvis Bay and Lüderitz (~25°S) shows vegetation changes in Congo, Angola and Namibia from the last glacial period into the Holocene. The comparison of pollen records from different latitudes provides information about the latitudinal shift of open forest and savannahs (Poaceae pollen), the extension of lowland forest (rain forest pollen) and Afromontane forest (Podocarpus pollen), and the position of the desert fringe (pollen of Caryophyllaceae, Chenopodiaceae and Amaranthaceae). High Cyperaceae pollen percentages in sediments from the last glacial period off the mouth of the river Congo suggest the presence of open swamps rather than savannah vegetation in the Congo Basin. Pollen from Restionaceae in combination with Stoebe-type pollen (probably from Elytropappus) indicates a possible northwards extension of winter rain vegetation during the last glacial period. The record of Rhizophora (mangrove) pollen is linked to erosion of the continental shelf and sea-level rise. Pollen influx is highest off river mouths (10-2000 grains year**-1 cm**-2), close to the coast (300-6000 grains year**-1 cm**-2), but is an order of magnitude lower at sites situated far from the continent (<10 grains year**-1 cm**-2).