The Genetic Origin of the Indo-Europeans.

The Yamnaya archaeological complex appeared around 3300BCE across the steppes north of the Black and Caspian Seas, and by 3000BCE reached its maximal extent from Hungary in the west to Kazakhstan in the east. To localize the ancestral and geographical origins of the Yamnaya among the diverse Eneolithic people that preceded them, we studied ancient DNA data from 428 individuals of which 299 are reported for the first time, demonstrating three previously unknown Eneolithic genetic clines. First, a "Caucasus-Lower Volga" (CLV) Cline suffused with Caucasus hunter-gatherer (CHG) ancestry extended between a Caucasus Neolithic southern end in Neolithic Armenia, and a steppe northern end in Berezhnovka in the Lower Volga. Bidirectional gene flow across the CLV cline created admixed intermediate populations in both the north Caucasus, such as the Maikop people, and on the steppe, such as those at the site of Remontnoye north of the Manych depression. CLV people also helped form two major riverine clines by admixing with distinct groups of European hunter-gatherers. A "Volga Cline" was formed as Lower Volga people mixed with upriver populations that had more Eastern hunter-gatherer (EHG) ancestry, creating genetically hyper-variable populations as at Khvalynsk in the Middle Volga. A "Dnipro Cline" was formed as CLV people bearing both Caucasus Neolithic and Lower Volga ancestry moved west and acquired Ukraine Neolithic hunter-gatherer (UNHG) ancestry to establish the population of the Serednii Stih culture from which the direct ancestors of the Yamnaya themselves were formed around 4000BCE. This population grew rapidly after 3750-3350BCE, precipitating the expansion of people of the Yamnaya culture who totally displaced previous groups on the Volga and further east, while admixing with more sedentary groups in the west. CLV cline people with Lower Volga ancestry contributed four fifths of the ancestry of the Yamnaya, but also, entering Anatolia from the east, contributed at least a tenth of the ancestry of Bronze Age Central Anatolians, where the Hittite language, related to the Indo-European languages spread by the Yamnaya, was spoken. We thus propose that the final unity of the speakers of the "Proto-Indo-Anatolian" ancestral language of both Anatolian and Indo-European languages can be traced to CLV cline people sometime between 4400-4000 BCE.

Selective amplification of maxicircle classes during the life cycle of Leishmania major.

The kinetoplast genome contains several thousands of minicircles of various sequence classes and several scores of maxicircles. We demonstrated that maxicircles are heterogeneous in clonal cultures of Leishmania major, and, therefore, probably heterogeneous (heteroplasmic) within the kinetoplast. Sequence heterogeneity was observed in a non-coding fragment upstream of the 12S rRNA gene. We identified about 20 stable variants of this fragment, which were composed of one to five non-identical repeats 200-300bp in length. Promastigote-to-amastigote and amastigote-to-promastigote differentiation was often accompanied by shifts in abundance of some maxicircle classes. Reversion to promastigote-specific maxicircle patterns was usually observed in the life cycle (promastigote-amastigote-promastigote), however there were many exceptions.

Radically different maxicircle classes within the same kinetoplast: an artefact or a novel feature of the kinetoplast genome?

We discuss here some results which suggest that radically different maxicircle classes coexist within the same kinetoplast. These data, although tentative and incomplete, may provide a new outlook on the kinetoplast genome structure and expression.

Conserved repeats in the kinetoplast maxicircle divergent region of Leishmania sp. and Leptomonas seymouri.

The maxicircle control region [also termed divergent region (DR)] composed of various repeat elements remains the most poorly studied part of the kinetoplast genome. Only three extensive DR sequences demonstrating no significant similarity were available for trypanosomatids (Leishmania tarentolae, Crithidia oncopelti, Trypanosoma brucei). Recently, extensive DR sequences have been obtained for Leishmania major and Trypanosoma cruzi. In this work we have sequenced DR fragments of Leishmania turanica, Leishmania mexicana, Leishmania chagasi and two monogenetic trypanosomatids Leptomonas seymouri and Leptomonas collosoma. With the emergence of the additional extensive sequences some conserved features of DR structure become evident. A conserved palindromic sequence has been revealed in the DRs of the studied Leishmania species, L. seymouri, and T. cruzi. The overall DR structure appears to be similar in all the Leishmania species, their relative L. seymouri, and T. brucei: long relatively GC-rich repeats are interspersed with clusters of short AT-rich repeats. C. oncopelti, L. collosoma, and T. cruzi have a completely different DR structure. Identification of conserved sequences and invariable structural features of the DR may further our understanding of the functioning of this important genome fragment.

The Leishmania major maxicircle divergent region is variable in different isolates and cell types.

The maxicircle divergent region (DR) was partially sequenced in several isolates of Leishmania major. The sequence contains various repeated elements: two types of long GC-rich repeats alternating with clusters of short AT-rich repeats. The arrangement of repeats appears to be similar in the studied Leishmania species and their relative Leptomonas seymouri. Furthermore, a conserved sequence containing putative promoters within a palindrome was revealed in the DRs of these species. Unexpectedly, the DR sequence proved to be dissimilar in promastigotes and amastigotes of the same isolate perhaps through selection of parasites with particular maxicircle variants in the course of the promastigote-amastigote differentiation. Different number of repeats and numerous single nucleotide polymorphisms are observed in the compared sequences. We have also investigated the DR structure in 21 L. major isolates by PCR and demonstrated its great variability. We suppose, however, that different variants of the DR structure are generated by combination of several highly conserved domains.